PEC Name
National Industrial Chemicals Notification and
Assessment Scheme
Methylcyclopentadienyl Manganese
Tricarbonyl (MMT)
________________________________________________________
Priority Existing Chemical
Assessment Report No. 24
June 2003
Commonwealth of Australia 2003
ISBN 0-9750516-6-0
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Priority Existing Chemical Assessment Report Number 24
ii
Preface
This assessment was carried out under the National Industrial Chemicals Notification and
Assessment Scheme (NICNAS). This Scheme was established by the Industrial Chemicals
(Notification and Assessment) Act 1989 (Cwlth) (the Act), which came into operation on 17
July 1990.
The principal aim of NICNAS is to aid in the protection of people at work, the public and
the environment from the harmful effects of industrial chemicals.
NICNAS assessments are carried out in conjunction with Environment Australia and the
Therapeutic Goods Administration, which carry out the environmental and public health
assessments, respectively.
NICNAS has two major programs: the assessment of the health and environmental effects
of new industrial chemicals prior to importation or manufacture; and the other focussing on
the assessment of chemicals already in use in Australia in response to specific concerns
about their health and/or environmental effects.
There is an established mechanism within NICNAS for prioritising and assessing the many
thousands of existing chemicals in use in Australia. Chemicals selected for assessment are
referred to as priority existing chemicals.
This priority existing chemical report has been prepared by the Director of NICNAS, in
accordance with the Act. Under the Act, manufacturers and importers of priority existing
chemicals are required to apply for assessment. Applicants for assessment are given a draft
copy of the report and 28 days to advise the Director of any errors. Following the
correction of any errors, the Director provides applicants and other interested parties with a
copy of the draft assessment report for consideration. This is a period of public comment
lasting for 28 days during which requests for variation of the report may be made. Where
variations are requested, the Director's decision concerning each request is made available
to each respondent and to other interested parties (for a further period of 28 days). Notices
in relation to public comment and decisions made appear in the Commonwealth Chemical
Gazette.
In accordance with the Act, publication of this report revokes the declaration of this
chemical as a priority existing chemical; therefore manufacturers and importers wishing to
introduce this chemical in the future need not apply for assessment. However,
manufacturers and importers need to be aware of their duty to provide any new information
to NICNAS, as required under Section 64 of the Act.
For the purposes of Section 78(1) of the Act, copies of assessment reports for new and
existing chemical assessments may be inspected by the public at the library of the National
Occupational Health and Safety Commission (NOHSC). Summary Reports are published in
the Commonwealth Chemical Gazette, which are also available to the public at the NOHSC
library.
Methylcyclopentadienyl manganese tricarbonyl (MMT) iii
Copies of this and other priority existing chemical reports are available on the NICNAS
web site. Hardcopies are available from NICNAS either by using the order form at the back
of this report, or directly from the following address:
GPO Box 58
Sydney
NSW 2001
AUSTRALIA
Tel: 1800 638 528
Fax: +61 (02) 8577 8888
Other information about NICNAS (also available on request and on the NICNAS web site)
includes:
? NICNAS Service Charter;
? information sheets on NICNAS Company Registration;
? information sheets on the Priority Existing Chemicals and New Chemical assessment
programs;
? safety information sheets on chemicals that have been assessed as priority existing
chemicals;
? details for the NICNAS Handbook for Notifiers; and
? details for the Commonwealth Chemical Gazette.
More information on NICNAS can be found at the NICNAS web site:
http://www.nicnas.gov.au
Other information on the management of workplace chemicals can be found at the web site
of the National Occupational Health and Safety Commission:
http://www.nohsc.gov.au
Priority Existing Chemical Assessment Report Number 24
iv
Overview
Anti-valve seat recession (AVSR) fuel additives were declared as Priority Existing
Chemicals for full assessment under the Industrial Chemicals (Notification and
Assessment) Act 1989 on 5 December 2000. They were nominated by the public because of
health and environmental concerns due to their increasing widespread use in automotive
lead replacement petrol (LRP). Four AVSRs have been notified for assessment:
methylcyclopentadienyl manganese tricarbonyl-based, phosphorous-based, sodium-based
and potassium-based additives.
AVSR fuel additives are available for both industrial and consumer use and are delivered
either by pre-blending to unleaded petrol at the oil refinery (LRP) or purchased and added
to unleaded petrol by the vehicle owner (known as aftermarket addition).
Methylcyclopentadienyl manganese tricarbonyl (MMT) (CAS # 12108-13-3) is a
manganese (Mn)-based AVSR imported predominantly for addition to LRP and in smaller
quantities for formulation of aftermarket fuel additives.
The natural attrition of older cars requiring AVSR additives means a decreasing AVSR
market and consequently the use of AVSR additives including MMT is likely to decline
with time. The production and infrastructure support of LRP will eventually become
economically unviable and aftermarket addition of AVSR additives will be the sole method
of providing valve seat protection through fuel. This report considered the occupational
health and safety, public health and environmental consequences of two separate scenarios
for the use of MMT ?a Present Use scenario assuming 100% market share and present
delivery modes and levels of demand, and a 2004 scenario assuming attrition of the AVSR
vehicle fleet, reduced demand and delivery of MMT via aftermarket addition only.
MMT is highly toxic to aquatic organisms. Spill incidents and leaks to water bodies and
land may potentially occur during shipment into Australia, bulk handling and storage and
leaks from underground storage tanks. These should be managed through existing Federal,
State and Territory legislative frameworks and protocols to mitigate adverse effects to the
aquatic environment.
Manganese, a by-product from combustion of MMT, is naturally occurring and ubiquitous
in the environment. It is an essential nutrient of plants and animals. Environmental
exposure to manganese compounds arising from combustion of MMT will mostly arise
through the gaseous phase. Eventually, these will deposit to land and waters. The emission
of manganese into the environment from use of fuels containing MMT is unlikely to
develop to levels of concern for terrestrial or aquatic environments. As such, the findings of
this assessment have not identified any significant risk to the environment given the
considered current use pattern of fuels containing MMT as an AVSR.
MMT is highly toxic in animals and humans. It is absorbed by all routes of exposure and
metabolised predominantly in the liver. Metabolites are excreted in urine and faeces. The
liver, kidney, brain and lung are the primary sites of Mn accumulation following MMT
absorption. The critical effects from acute exposure to MMT are neurological and
pulmonary dysfunction. Acute lethal exposure to MMT in animals is associated with
damage to the lungs by all routes, kidney, liver and spleen effects, tremors, convulsions,
dyspnea and weakness. In humans, giddiness, headache, nausea, chest tightness, dyspnea
Methylcyclopentadienyl manganese tricarbonyl (MMT) v
and paresthesia are reported in anecdotal cases of acute occupational exposure. Repeated
inhalation exposure to MMT in animals results in degenerative changes in liver and
kidneys.
MMT (as Mn) is currently listed in the NOHSC List of Designated Hazardous Substances
with no classification. Based on assessment of health effects, this report has concluded that
MMT meets the NOHSC Approved Criteria for Classifying Hazardous Substances for
classification on the basis of acute lethal effects by all exposure routes and severe effects
after repeated or prolonged exposure via inhalation. The following risk and safety phrases
are recommended: R26 - Very Toxic by Inhalation; R28 ?Very Toxic if Swallowed; R24 ?br>
Toxic in Contact with Skin; R48/23 ?Toxic: Danger of Serious Damage to Health by
Prolonged Exposure Through Inhalation; S36 - Wear Suitable Protective Clothing; S38 - In
Case of Insufficient Ventilation Wear Suitable Respiratory Equipment.
As MMT is combusted to a number of inorganic Mn species, the health hazards associated
with the use of MMT also include those associated with inorganic Mn. In animals and
humans, neurological dysfunction is the critical effect following acute exposure to Mn
compounds. Decreased activity, alertness, muscle tone, touch response and respiration are
reported in animal studies. In humans, chronic occupational exposure to respirable Mn
dusts is associated with subclinical nervous system toxicity through to overt manganism, a
progressive neurological disorder characterised by altered gait, tremor and occasional
psychiatric disturbances.
Minimal occupational exposure to MMT is likely for workers involved in formulating and
distributing LRP or aftermarket fuel additives and those involved in automotive
maintenance. Overall, a low occupational risk associated with MMT was concluded.
Occupational exposure to Mn, mainly via inhalation, may occur also for these and other
workers associated with or in the vicinity of automotive usage. Where automotive usage is
ubiquitous, chronic inhalation of inorganic Mn species may result. In the absence of
Australian occupational exposure data, a worst-case scenario was considered for Mn
exposure of Australian auto mechanics from the use of MMT using overseas personal
inhalational exposure estimates. A low occupational risk associated with Mn exposure from
MMT combustion was concluded.
Minimal public exposure to MMT is likely as a result of spills and splashes of LRP and
aftermarket additives. A low risk is concluded. A similar low risk is envisaged from MMT
in LRP given the lower concentrations of MMT compared to aftermarket additives.
Acute health effects could occur as a result of accidental ingestion of MMT by a child or by
adults when siphoning fuel. The health risk to adults from accidental ingestion of LRP
containing MMT during siphoning or to children following ingestion of LRP stored
inappropriately around the home is considered low, given the low level of MMT in LRP.
However, a comparison between the potential oral dose of MMT from accidental ingestion
of aftermarket additive by a child and animal oral LD50 values indicates that MMT
represent a significant acute health risk for children.
Although the public use of MMT may increase ambient air Mn levels and therefore doses
received by inhalation, given that the predominant sources of Mn for humans via food and
water are unlikely to be altered significantly by the use of MMT, overall chronic Mn
exposures (from all sources combined) are unlikely to change significantly. The margins of
exposure for the public are greater than 1000. The estimated ambient air concentration of
Mn due to MMT combustion according to the Present Use scenario is less than a range of
Priority Existing Chemical Assessment Report Number 24
vi
overseas inhalation health standards and guidance values. Given the conservative
assumptions used in the exposure assessment, the overall public health risk from the use of
MMT as an AVSR is low.
This report has identified the need particularly to reduce public exposure to MMT as much
as practicable. Given its toxicity profile and consumer use, it is recommended that the
National Drugs and Poisons Schedule Committee (NDPSC) consider scheduling MMT on
the Standard for Uniform Scheduling of Drugs and Poisons (SUSDP). It is recommended
also that consumer packaging be of a design to facilitate the accurate addition of additive to
fuel tanks without spillage and incorporate an automatic measuring and dispensing capacity
and child-proof closures.
This report encourages the monitoring of ambient air Mn to more accurately estimate the
risk to the public. It also supports research into the effects of fuel-related Mn emissions
especially on susceptible subpopulations such as children.
Methylcyclopentadienyl manganese tricarbonyl (MMT) vii
Contents
PREFACE iii
OVERVIEW v
ABBREVIATIONS xv
1. INTRODUCTION 1
1.1 Declaration 1
1.2 Objectives 1
1.3 Sources of information 1
1.4 Peer review 2
2. BACKGROUND 3
2.1 What is an anti-valve seat recession additive? 3
2.2 International perspective 4
2.3 Australian perspective 5
2.4 Assessments by other national or international bodies 6
3. APPLICANTS 7
4. CHEMICAL IDENTITY AND COMPOSITION 8
4.1 Chemical identity 8
4.2 Composition of commercial products 8
5. PHYSICAL AND CHEMICAL PROPERTIES 10
5.1 Physical state 10
5.2 Physical properties 10
5.3 Chemical properties 10
o
5.4 Conversion factors (at 25 C) 10
6. METHODS OF DETECTION AND ANALYSIS 11
6.1 Identification 11
6.2 Atmospheric monitoring methods 11
6.3 Biological monitoring methods 11
6.4 Water monitoring methods 12
6.5 Petrol monitoring methods 12
Priority Existing Chemical Assessment Report Number 24
viii
6.6 Soil monitoring methods 12
7. IMPORTATION AND USE OF MMT 13
7.1 Importation 13
7.2 Uses 13
7.2.1 Demand for anti-valve seat recession additives 13
7.2.2 Use scenarios 14
8. EXPOSURE 17
8.1 Environmental exposure 17
8.1.1 Use of MMT as an AVSR Agent 17
8.1.2 Release of MMT 18
8.1.3 Exhaust release of manganese compounds from
combustion of MMT 19
8.1.4 Emission rate and physical form of manganese in exhaust
gases 20
8.1.5 Effect of MMT on exhaust gases (NOx, CO, CO2,
hydrocarbons, particulates) and onboard pollution control
equipment 22
8.2 Fate 24
8.2.1 Atmosphere 24
8.2.2 Water 24
8.2.3 Soils and sediments 25
8.2.4 Fate of inorganic compounds from combustion of MMT 25
8.3 Environmental concentrations of MMT and manganese 26
8.3.1 MMT 26
8.3.2 Manganese in the atmosphere in Canada 26
8.3.3 Manganese in the atmosphere in Australia 28
8.3.4 Release of Mn to the water compartment 31
8.4 Occupational exposure to MMT 32
8.4.1 Bulk fuel and fuel additive blending at refineries and
formulators 32
8.4.2 Petrol stations and maintenance workshops 33
8.5 Occupational exposure to manganese from MMT use 33
8.5.1 Exposure data and estimates 34
8.6 Public exposure 37
8.6.1 Consumer exposure 37
8.6.2 Indirect exposure via environment 38
9. KINETICS AND METABOLISM OF MMT 44
9.1 Absorption 44
Methylcyclopentadienyl manganese tricarbonyl (MMT) ix
9.2 Distribution 44
9.3 Metabolism 46
9.4 Elimination and excretion 47
9.5 Summary 49
10. TOXICITY OF MMT 50
10.1 Acute toxicity 50
10.2 Irritation and corrosivity 52
10.2.1 Skin 52
10.2.2 Eye 53
10.3 Sensitisation 53
10.4 Repeated dose toxicity 54
10.5 Reproductive toxicity 55
10.6 Genotoxicity 57
10.7 Carcinogenicity 58
10.8 Pulmonary toxicity 58
10.9 Neurotoxicity 61
10.10 MMT combustion products 63
10.11 Human exposure 65
11. PHARMACOKINETICS AND TOXICITY OF MANGANESE 66
11.1 Kinetics and metabolism 66
11.2 Human health effects 68
11.3 Effects in animals 70
12. HAZARD CLASSIFICATION 73
12.1 Physicochemical hazards 73
12.2 Health hazards 73
12.2.1 Acute toxicity 73
12.2.2 Irritation and corrosive effects 74
12.2.3 Sensitising effects 74
12.2.4 Effects from repeated or prolonged exposure 74
12.2.5 Reproductive effects 75
12.2.6 Genotoxicity 76
12.2.7 Carcinogenicity 76
13. EFFECTS ON ORGANISMS IN THE ENVIRONMENT 77
13.2 Terrestrial animals 78
13.2.1 MMT 78
13.2.2 Manganese 78
Priority Existing Chemical Assessment Report Number 24
x
13.3 Terrestrial plants 78
13.3.1 MMT 78
13.3.2 Manganese 78
13.4 Aquatic plants 79
13.4.1 MMT 79
13.4.2 Manganese 79
13.5 Aquatic invertebrates 80
13.5.1 MMT 80
13.5.2 Manganese 81
13.6 Fish 84
13.6.1 MMT 84
13.6.2 Manganese 85
13.7 Amphibians 87
13.7.1 MMT 87
13.7.2 Manganese 87
13.8 Summary of environmental effects 87
13.8.1 MMT 87
13.8.2 Manganese 87
14. RISK CHARACTERISATION 89
14.1 Environmental risk 89
14.1.1 Terrestrial risk 89
14.1.2 Aquatic risk 90
14.2 Occupational risk 90
14.2.1 Critical health effects 91
14.2.2 Occupational health and safety risks 92
14.2.3 Uncertainties 93
14.3 Public health risk 94
14.3.1 Acute effects 94
14.3.2 Chronic effects 95
14.3.3 Uncertainties 97
15. RISK MANAGEMENT 98
15.1 Assessment of current control measures 98
15.1.1 Elimination and substitution 98
15.1.2 Isolation and engineering controls 98
15.1.3 Safe work practices 99
15.1.4 Personal protective equipment 100
15.2 Hazard communication 100
15.2.1 Labels 100
Methylcyclopentadienyl manganese tricarbonyl (MMT) xi
15.2.2 MSDS 102
15.2.3 Education and training 103
15.3 Occupational monitoring and regulatory controls 103
15.3.1 Atmospheric monitoring 103
15.3.2 Occupational exposure standards 104
15.3.3 Health surveillance 105
15.3.4 National transportation regulations 105
15.3.5 National storage and handling regulations 106
15.3.6 Control of major hazard facilities 106
15.4 Public health regulatory controls 106
15.5 Environmental regulatory controls 107
15.5.1 Air quality management 107
15.5.2 Aquatic ecosystem management 108
15.5.3 Disposal and waste treatment 109
15.6 Emergency procedures 109
16. DISCUSSION AND CONCLUSIONS 111
16.1 Health hazards 111
16.2 Environmental hazards and risks 113
16.3 Occupational health and safety risks 114
16.4 Public health risks 115
16.5 Data gaps 116
17. RECOMMENDATIONS 118
17.1 Recommendations for regulatory bodies 118
17.1.1 NOHSC 118
17.1.2 National Drugs and Poisons Schedule Committee 118
17.1.3 Tasmanian Department of Primary Industries, Water and
Environment 118
17.2 Recommendations for MMT importers and formulators of MMT
products 119
17.2.1 Hazard communication ?MSDS 119
17.2.2 Hazard communication ?labels 119
17.2.3 Packaging 119
17.2.4 Emergency procedures 120
18. SECONDARY NOTIFICATION 121
APPENDIX 1 - CALCULATION OF LRP VOLUMES FOR 2004 122
APPENDIX 2 - MSDS ASSESSMENT SUMMARY 123
Priority Existing Chemical Assessment Report Number 24
xii
APPENDIX 3 - SAMPLE MATERIAL SAFETY DATA SHEET FOR
METHYLCYCLOPENTADIENYL MANGANESE TRICARBONYL (MMT) 125
APPENDIX 4 ?CLASSIFICATION UNDER THE GLOBALLY HARMONIZED
SYSTEM FOR HAZARD CLASSIFICATION AND COMMUNICATION 130
REFERENCES 131
LIST OF TABLES
Table 1. Physical properties of MMT 10
Table 2. Summary of the AVSR additive use scenarios 15
Table 3. Emission data for MMT use (Lenane et al., 1994) 23
Table 4. Emission data for MMT use (AAM, 2002) 23
Table 5. Outdoor monitoring levels of microenvironmental Mn and MMT in Montreal, Canada
(Zayed et al; 1999a) 27
Table 6. Mn content of particulate matter (PM) in the atmosphere of Australian cities (Ayers et al.,
1999) 28
Table 7. Estimated average and reasonable maximum atmospheric Mn levels in Sydney ?various
MMT use scenarios and conditions 31
Table 8. Personal total manganese exposure of Montreal taxi drivers and garage mechanics
(Zayed et al., 1994) 36
Table 9. Personal total manganese exposure of Montreal garage mechanics and non-automotive
workers (Sierra et al., 1995) 36
Table 10. Lifetime average estimated human exposure to Mn in ambient air 40
Table 11. Summary of main sources of human exposure to Mn 43
Table 12. Summary of MMT acute lethality studies 50
Table 13. Tumour Incidence in MMT Treated Mice 58
Table 14. Summary of aquatic toxicity data for MMT and manganese 77
Table 15. Summary of aquatic phytotoxicity data for manganese 80
Table 16. Summary of freshwater invertebrate toxicity data for manganese 81
Table 17. Summary of saltwater/marine invertebrate toxicity data for Manganese 83
Methylcyclopentadienyl manganese tricarbonyl (MMT) xiii
Table 18. Summary of freshwater fish toxicity data (TLm mg/L) for MMT 84
Table 19. Summary of freshwater fish toxicity data for manganese 85
Table 19. Occupational exposure limits for MMT and elemental and inorganic manganese
compounds 104
LIST OF FIGURES
Figure 1. Exhaust valve recession into the cylinder head. From: Barlow (1999) 3
Figure 2. The number of vehicles requiring leaded or lead-replacement petrol 16
Priority Existing Chemical Assessment Report Number 24
xiv
Abbreviations
ACGIH American Conference of Governmental Industrial Hygienists
ADG Code Australian Code for the Transport of Dangerous Goods by Road
and Rail
AMSA Australian Maritime Safety Authority
ANZECC Australian and New Zealand Environment and Conservation
Council
AOAA aminooxyacetic acid
aq aqueous
ARMCANZ Agriculture and Resource Management Council of Australia and
New Zealand
ATSDR Agency for Toxic Substances and Disease Registry
ABS Australian Bureau of Statistics
AVSR anti-valve seat recession
bw body weight
CAA Clean Air Act
CAS Chemical Abstracts Service
CC16 Clara cell protein
CID cubic inch displacement
maximum concentration
Cmax
CMT carboxycyclopentadienyl manganese tricarbonyl
DNA deoxyribonucleic acid
DOPAC 3,4-dihydroxyphenylacetic acid
EA Environment Australia
median effective concentration
EC50
EINECS European Inventory of Existing Commercial Chemical
Substances
FORS Federal Office of Road Safety
g gram
Methylcyclopentadienyl manganese tricarbonyl (MMT) xv
GABA 4-aminobutyric acid
h hour
HAPS hazardous air pollutants
HMT hydroxymethylcyclopentadienyl manganese tricarbonyl
HQ hazard quotient
HVA homovanillic acid
25th percentile inhibitory concentration
IC25
IC50 median inhibitory concentration
IIWL interim indicative working level
IMO International Maritime Organisation
ip intraperitoneal
IPCS International Programme on Chemical Safety
iv intravenous
kg kilogram
Michaelis constant
Km
L litre
LC50 median lethal concentration
LD50 median lethal dose
LOAEL lowest-observed-adverse-effect level
LRP lead replacement petrol
LT50 median lethal time
礸 microgram
祄 micrometre
MATC maximum acceptable threshold concentration
ML megalitre
mg milligram
mL millilitre
MMT methylcyclopentadienyl manganese tricarbonyl
Mn manganese
MOE margin of exposure
Priority Existing Chemical Assessment Report Number 24
xvi
MSDS Material Safety Data Sheet
m3 cubic metre
NAPS National Air Pollution Surveillance
NDPSC National Drugs and Poisons Schedule Committee
NEPC National Environment Protection Council
NEPM National Environment Protection Measure
ng nanogram
NHMRC National Health and Medical Research Council
NICNAS National Industrial Chemicals Notification and Assessment
Scheme
NOAEL no-observed-adverse-effect level
NOEC no-observed-effect concentration
NOEL no-observed-effect level
NOHSC National Occupational Health and Safety Commission
NOS not otherwise specified
NPI National Pollution Inventory
OECD Organisation for Economic Cooperation and Development
PEC predicted environmental concentration
PNEC predicted no-effect concentration
PPE personal protective equipment
ppm parts per million
RfC reference concentration
ROS reactive oxygen species
SEM scanning electron microscopy
SUSDP Standard for the Uniform Scheduling of Drugs and Poisons
half-life
T1/2
TBOB t-butylbicycloorthobenzoate
TGA Therapeutic Goods Administration
TLm median threshold limit
maximum time
Tmax
Methylcyclopentadienyl manganese tricarbonyl (MMT) xvii
TWA time-weighted average
UKDETR United Kingdom Department of Environment, Transport and
Regions
USEPA United States Environmental Protection Agency
maximum enzymatic velocity
Vmax
VSR valve seat recession
WHO World Health Organisation
Priority Existing Chemical Assessment Report Number 24
xviii
1. Introduction
1.1 Declaration
Anti-valve seat recession (AVSR) fuel additives were declared as Priority Existing
Chemicals for full assessment under the Industrial Chemicals (Notification and
Assessment) Act 1989 on 5 December 2000. They were nominated because of their
increasing widespread use in lead replacement petrol (LRP) and potential adverse
effects on the environment and human health.
Applications for the following AVSRs in use in Australia were received:
? Methylcyclopentadienyl Manganese Tricarbonyl (MMT)-based;
? Phosphorous-based;
? Sodium-based; and
? Potassium-based.
Each AVSR fuel additive has been assessed individually and separate reports are
prepared for each. This present report addresses the use of MMT (CAS # 12108-13-3)
as an AVSR.
1.2 Objectives
The objectives of this assessment are to:
? Characterise the chemical and physical properties of MMT;
? Determine the current and potential occupational, public and environmental
exposure to MMT as an AVSR;
? Characterise the intrinsic capacity of MMT to cause adverse effects on persons
or the environment;
? Characterise the risk to humans and the environment resulting from exposure to
MMT as an AVSR;
? Determine the extent to which any risk is capable of being reduced and make
recommendations for the management of these risks.
1.3 Sources of information
Consistent with these objectives, the report presents a summary and critical evaluation
of relevant information relating to the potential health and environmental hazards from
exposure to MMT. Relevant scientific data were submitted by the applicants listed in
Section 3, obtained from published papers identified in a comprehensive literature
search of several online databases up to August 2002, or retrieved from other sources
such as the reports and resource documents prepared by overseas regulatory bodies.
Methylcyclopentadienyl manganese tricarbonyl (MMT) 1
Due to the availability of detailed overseas regulatory reviews e.g. Risk Assessment for
the Combustion Products of Methylcyclopentadienyl Manganese Tricarbonyl (MMT) in
Gasoline (Wood and Egyed, Health Canada, 1994), Reevaluation of Inhalation Health
Risks Associated with Methylcyclopentadienyl Manganese Tricarbonyl (MMT) in
Gasoline, (USEPA 1994c), Environmental Health Criteria 17: Manganese (WHO
1981), Concise International Chemical Assessment Document 12 ?Manganese and Its
Compounds (WHO 1999) and Toxicological Profile for Manganese (Update) (ATSDR
2000), not all primary source data were evaluated. However, relevant studies published
since the cited reviews were assessed on an individual basis.
The characterisation of health and environmental risks in Australia was based upon
information on use patterns, product specifications, occupational exposure and
emissions to the environment made available by the applicant and relevant State and
Federal authorities. Information to assist in the assessment was also obtained through
site visits and telephone interviews.
1.4 Peer review
During all stages of the preparation, the report has been subject to peer review by
NICNAS, Environmental Australia (EA) and the Therapeutic Goods Administration
(TGA). In addition, selected parts of the report were peer reviewed by overseas
authorities. Dr. J. Michael Davis of the National Centre for Environmental Assessment-
RTP, Office of Research and Development, United States Environmental Protection
Agency and Dr. Barry Jessiman, Air Health Effects Division, Air and Fuel Assessment
Section, Health Canada provided valuable comment focussing on exposure and risk
characterisation.
Priority Existing Chemical Assessment Report Number 24
2
2. Background
Methylcyclopentadienyl manganese tricarbonyl (MMT) was first developed in the
1950s by the Ethyl Corporation. MMT is an organometallic compound produced either
by the reaction of manganous chloride, cyclopentadiene, and carbon monoxide in the
presence of manganese carbonyl and a group II or IIIA element, or the reaction of
methylcyclopentadiene with manganese carbonyl. MMT is used as an antiknock agent
in internal combustion engine fuels (Davis 1998). In more recent times, MMT has also
been marketed as an anti-valve seat recession (AVSR) additive for lead replacement
petrol (LRP).
2.1 What is an anti-valve seat recession additive?
Anti-valve seat recession fuel additives are added to petrol to stop excessive valve seat
wear and recession of the valve seat into the automotive engine cylinder head (Figure
1).
Figure 1. Exhaust valve recession into the cylinder head. From: Barlow (1999)
Although valve seat recession (VSR) occurs as part of the normal wear of an engine,
premature erosion of the valve seats observed as excessive VSR occurs when vehicles
with soft exhaust valve seats normally designed to operate on leaded petrol are operated
on unleaded petrol.
Valve seats in engines designed for leaded fuel are generally relatively soft. With
leaded fuels, lead oxide formed by the combustion of lead alkyls forms a thin layer of
lead oxide on the valve and valve seat, so acting as a solid lubricant and preventing
erosion of the valve seats in the cylinder head of the engine (Figure 1). VSR can cause
valve burning and loss of compression and if allowed to progress result in serious loss
of performance and ultimately engine failure. Lead replacement petrol uses AVSR
additives to provide the lubricating qualities previously provided by lead. During fuel
combustion, the AVSR additive burns and forms an oxide coating on the exhaust valve
seats providing similar protective lubrication to lead oxide.
Methylcyclopentadienyl manganese tricarbonyl (MMT) 3
Since the early 1970s, increasing environmental and health concerns have resulted in
the reduction of lead levels in petrol and the complete removal of leaded gasoline in
several countries (Lovei, 1998). In 2000, the World Bank reported that 36 countries had
already phased out the use of leaded petrol and this was expected to increase to 55
countries by 2005 (Benbarka, 2000). In addition, the use of catalytic converters in
automotive exhaust systems required the introduction of unleaded fuels as lead destroys
the capacity of catalytic converters to reduce other pollutants (Lovei, 1998).
A consequence of the removal of lead from petrol is that engine designers have been
required to use harder exhaust valve seat materials that maintain integrity without lead
lubrication. For existing cars with soft valve seats, the removal of lead has required
motorists to use lead replacement petrol containing an AVSR additive or to modify
their engine by fitting hardened exhaust valve seats suitable for unleaded petrol with no
AVSR fuel additive (Lovei 1998).
The use of AVSR additives has risen with the demand for lead replacement petrol
resulting from the lead phase-out worldwide. The demands for lead replacement petrol
and hence AVSR additives in individual countries have been determined largely by
policy decisions regarding the import, sale and retirement of older vehicles, the
encouragement of new technology environmentally cleaner engines and improved
petrol standards. Consequently, the population of VSR sensitive cars and thus demand
for AVSR additives in lead replacement petrol vary from country to country.
2.2 International perspective
MMT has been used in internal combustion engine fuels in the United States since
1976. In 1977, the passing of the Clean Air Act in the United States (US Congress
1977) limited the use of MMT to leaded gasoline. The basis of this decision was that
MMT had detrimental effects on catalytic converters in unleaded vehicles, resulting in
increased hydrocarbon emissions. Between 1977 and 1993 Ethyl Corporation
unsuccessfully applied to the United States Environmental Protection Agency (USEPA)
on several occasions for a waiver to use MMT in unleaded fuel in the United States.
Based on extensive additional emission data submitted by Ethyl Corporation, the
USEPA concluded in November 1993 that MMT did not increase hydrocarbon
emissions. However, in July 1994 the USEPA again denied the waiver application by
Ethyl Corporation, based on possible adverse health effects of an increase in airborne
manganese (Mn) resulting from MMT use (USEPA 1994a). Ethyl Corporation
subsequently challenged this decision in the United States Federal Court (Ethyl
Corporation v. USEPA 1995a). The Federal Court ruled that the USEPA had no
grounds to deny Ethyl Corporation's application except if MMT caused or contributed
to the failure of any emission device or system.
In May 1994, the fuel or fuel additive rule (USEPA 1994b), as mandated in the Clean
Air Act (US Congress 1977), was issued by the USEPA requiring all fuel or fuel
additive manufacturers to provide specific mammalian toxicity studies. Furthermore,
the marketing of products not registered by the USEPA was prohibited until the specific
toxicity studies were provided. The USEPA subsequently claimed that MMT was not
registered, but Ethyl Corporation successfully challenged this position (Ethyl
Corporation v. USEPA 1995b) and has been marketing MMT in the United States since
December 1995. However, the studies specified by the USEPA on MMT as well as
other fuel additives must still be conducted (Wood and Egyed 1994; Davis 1998). At
Priority Existing Chemical Assessment Report Number 24
4
the time of writing, according to Ethyl, some studies have been completed. The use of
MMT, especially in the United States, remains controversial (Landrigan 2001).
The use of MMT in combustion engine fuels has been permitted in Canada since 1978.
At this time a review of MMT by the Canadian Department of Health and Welfare
concluded that its use as a fuel additive did not constitute a hazard to human health
(Health and Welfare Canada 1978). In 1985, the Canadian Royal Commission on Lead
in the Environment examined MMT as part of a review on lead additives and lead
substitutes in combustion engine fuel. The conclusions reached were similar to those in
1978 (Royal Society of Canada 1986). During the next two years, two independent
studies were prepared under contract from Health and Welfare Canada. The first
incorporated recently completed toxicity studies (Midwest Research Institute 1987)
while the second completed an exposure assessment (Hill 1988). Again, both reports
reached similar conclusions to those formed in 1978.
In 1994, Health Canada performed a risk assessment of the health issues arising from
the use of MMT in fuel in Canada, focusing on new epidemiological studies and
Canadian exposure data (Wood and Egyed 1994). These authors concluded that the use
of MMT in fuel posed no added health risk to the general population. However, in
1997, trade in MMT was restricted in Canada under the Manganese-based Fuel
Additives Act that effectively banned the importation of MMT into Canada. This Act
was subsequently and successfully challenged on the grounds that it contravened the
Agreement on Internal Trade (AIT). The AIT is an agreement between the federal and
provincial governments designed to prevent arbitrary trade barriers within the country.
In 1998, the Government of Canada announced that it had removed restrictions on
inter-provincial trade and import of MMT (Davis 1998). However, the use of MMT in
Canadian fuel is still the subject of debate and health and environmental uncertainties
remain (Zayed et al., 2001).
In addition to the US and Canada, the use of MMT is permitted in France (Minestre de
L'Amenagement du Territoire et de L'Environment 1999), UK (British Standards
Institute 1999), China (China State Bureau of Quality and Technology Supervision
2000), Russia (Ministry of Fuel and Energy of Russian Federation 1997), and
Argentina (Norma Argentina 1999).
In New Zealand, as a result of promulgation of the Petroleum Products Specifications
Regulations 2002, effective from 1 September 2002 automotive fuel must contain no
more than 2.0 mg/L Mn. The background behind this decision is not known. The
limitation on Mn content of fuels is to be reviewed by 2006. This law effectively
severely restricts the use of MMT in automotive fuels in New Zealand.
2.3 Australian perspective
In Australia, under the Fuel Quality Standards Act 2000 (Cwlth) lead was removed
from automotive fuel from 1 January 2002 requiring the use of alternative additives for
valve seat protection. Under this Act, provision is made for listing of prohibited fuel
additives. MMT is not currently listed.
An Australian Standard AS 4430.1 - 1996 (Standards Australia, 1996) exists for the
evaluation of devices and additives which claim to improve vehicle performance. Part 1
of AS 4430.1 ?1996 is noteworthy for the present report as it considers engines
Methylcyclopentadienyl manganese tricarbonyl (MMT) 5
designed for leaded fuel to operate on unleaded fuels and includes assessment of valve
seat recession.
An environmental and epidemiological study of Mn from MMT use is currently being
conducted in Australia. The objectives of the project are to determine the contribution
of MMT use to Mn levels in air, dust, soil and water and also blood and urine Mn levels
in children aged 1-5 years.
2.4 Assessments by other national or international bodies
Reviews of the health and environmental effects associated with the use of MMT in
combustion engine fuels were released in 1994 by the Environmental Health
Directorate, Health Canada (Wood and Egyed 1994) and the USEPA (USEPA 1994c).
Further, detailed overseas regulatory reviews of Mn have been conducted e.g.
Environmental Health Criteria 17: Manganese (WHO 1981), Concise International
Chemical Assessment Document 12 ?Manganese and Its Compounds (WHO 1999)
and Toxicological Profile for Manganese (Update) (ATSDR 2000).
Priority Existing Chemical Assessment Report Number 24
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3. Applicants
Ethyl Asia Pacific Company
PO Box 285
North Sydney NSW 2059
Wynn's Australia Pty Ltd
PO Box 6096
French's Forest Delivery Centre NSW 1640
Nulon Products Australia Pty Ltd
114 Narabang Way
Belrose NSW 2085
Methylcyclopentadienyl manganese tricarbonyl (MMT) 7
4. Chemical Identity and
Composition
4.1 Chemical identity
Chemical Name: Manganese tricarbonyl [(1,2,3,4,5-eta)-
1-methyl-2,4-cyclopentadien-1-yl]-
CAS No.: 12108-13-3
EINECS No.: 235-166-5
Synonyms: MMT, Methylcyclopentadienyl
manganese tricarbonyl,
Methylcymantrene
Trade Names: AK-33X, Antiknock-33, CI-2,
Combustion Improver-2.
C9H7MnO3
Molecular Formula:
Me
Me
Structural Formula:
-
C
HC CH
HC CH
+
Mn
CO
OC
CO
Molecular Weight: 218
4.2 Composition of commercial products
The Ethyl Asia Pacific Company markets two MMT-containing products. HiTEC 3062
contains 62% MMT w/w in a mixed aromatic and aliphatic solvent and HiTEC 3000
contains neat MMT. At the time of writing, HiTEC 3000 is not being imported to
Australia.
Wynn's Australia Pty Ltd markets two MMT-containing products. Spitfire Octane
Boost and Race Formula Octane Boost both contain < 5% w/w MMT in petroleum
distillate.
Priority Existing Chemical Assessment Report Number 24
8
Nulon Products Australia Pty Ltd markets three MMT-containing products. Octane
Boost and Clean and Total Fuel System Cleaner both contain < 5% w/w MMT whilst
Pro Strength Octane Booster contains < 10% w/w MMT, all in petroleum distillate.
Methylcyclopentadienyl manganese tricarbonyl (MMT) 9
5. Physical and Chemical Properties
5.1 Physical state
MMT is a dark orange or yellow liquid with a faintly pleasant or herbaceous odour
(Lewis 1996).
5.2 Physical properties
Table 1. Physical properties of MMT
Property Value Reference
231.67oC
Boiling point ACGIH, 1991
2.22oC
Melting point Ethyl Submission
Density at 20oC 1390 kg/m3 ACGIH, 1991
Water solubility at 25oC 0.029 g/L Ethyl Submission
Vapour pressure at 100oC 1.24 kPa Zenz , 1988
at 20oC 0.01 kPa Ethyl Submission
<10-9 Pa m3/mol Ethyl Submission
Henry's law constant
Partition coefficient (log Pow) 3.4 Ethyl Submission
257oC
Autoignition temperature Ethyl Submission
Ethyl Submission
Flammability Limits Lower: 0.3% at
153oC
Upper: 26% at
175oC
96oC
Flash point (closed cup) Zenz, 1988
5.3 Chemical properties
Solubility: MMT is miscible in most hydrocarbon solvents (Kirk-Othmer 1967).
Stability: MMT decomposes when exposed to light (Kaufman et al., 1961).
Polymerisation: MMT will not undergo hazardous polymerisation.
Conversion factors (at 25oC)
5.4
1 mg/m3 = 8.93 ppm 1 ppm = 0.11 mg/m3
Priority Existing Chemical Assessment Report Number 24
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6. Methods of Detection and
Analysis
6.1 Identification
The detection and determination of MMT is usually achieved by using chromatography
together with spectrophotometry. In addition, a number of methods have been described
for indirect MMT determinations based on total Mn concentrations.
6.2 Atmospheric monitoring methods
A gas chromatographic protocol has been developed to determine MMT in ambient air.
The limit of detection using this protocol is 0.05 ng/m3. MMT is trapped on Teflon-
lined U-tubes packed with 3% OV-1 on Chromosorb W. During sampling the U-tubes
are placed in a water-ice cooling bath and air is pumped through the U-tube at
approximately 70 mL/min using a vacuum pump. Determination is made by gas
chromatography with an electrothermal atomic absorption detector (Coe et al., 1980).
A similar procedure to Coe et al. (1980) for the determination of MMT in ambient air is
described by Gaind et al. (1992). Airborne MMT is collected in XAD-2 containing
tubes using an air-sampling pump. Determination is made by gas chromatography with
an electron capture detector. The limit of detection using this protocol is 0.001 mg/m3
from a 10 L air sample.
A procedure for the determination of organic Mn in personal air samples has been
described by Albemarle Corporation (1994). Determination is achieved by adsorption
onto activated charcoal, followed by desorption by nitric acid, and then atomic
absorption spectrophotometry. This protocol is applicable to organic Mn concentrations
below 3 礸 Mn/mL nitric acid. The method does not distinguish between different
organic Mn species. A glass fibre filter is attached to the front of the charcoal tube to
remove inorganic (particulate) Mn.
A number of methods have been described for the determination of inorganic Mn in
ambient air. These include x-ray fluorescence and inductivity coupled plasma atomic
emission spectrophotometry (ATSDR 2000).
6.3 Biological monitoring methods
A gas chromatography protocol has been developed to determine MMT in biological
tissues or fluids. MMT present in small biological samples or fluids is extracted into
hexane containing biphenyl as an internal standard followed by gas chromatography
utilising a flame ionisation detector. As little as 1-2 ppm MMT can be quantified using
this method (Hanzlik et al., 1979).
More recently, Walton et al., (1991) have described a method that combines high-
performance liquid chromatography with laser-excited atomic fluorescence for the
Methylcyclopentadienyl manganese tricarbonyl (MMT) 11
detection of MMT in urine. The limit of detection was 1.6 ng/mL. This method was
also able to distinguish MMT from several MMT-derived metabolites.
A number of techniques have been described for the determination of inorganic Mn in
biological fluids and tissues. These include flame atomic absorption analysis, furnace
atomic absorption analysis, neutron activation analysis, spectrophotometry, mass
spectrometry, and x-ray fluorimetry (ATSDR 2000).
6.4 Water monitoring methods
A gas chromatography protocol has been developed to determine trace amounts of
MMT in water. This protocol is applicable to MMT concentrations in water of 0.05-10
ppm (the solubility limit of MMT). All samples and standards must be protected from
light because solutions of water (and other solvents) are photolytic. A water sample is
mixed with carbon disulfide, the carbon disulfide layer is then removed, and the MMT
quantified by gas chromatography (Ethyl Corporation 1989).
A number of techniques have been described for the determination of inorganic Mn in
water samples. These include inductivity coupled plasma atomic emission analysis,
atomic absorption spectrophotometry, catalytic kinetic analysis and colourmetric
analysis (ATSDR 2000).
6.5 Petrol monitoring methods
A number of procedures have been described for the determination of MMT in petrol.
All utilise gas chromatography, with either an electron capture detector (Giand et al.,
1992), argon plasma emission detector (Uden et al., 1978; Ombana and Barry 1994),
flame photometric detector (Aue et al., 1990), or atmospheric pressure helium
microwave detector (Quimby et al., 1978).
A gas chromatography atomic emission spectroscopy protocol has been developed to
determine organic Mn in petrol. This protocol requires minimal sample preparation and
is able to quantify and speciate trace organic Mn levels (Swan 1999).
6.6 Soil monitoring methods
An atomic absorption spectrophotometic protocol has been developed to determine
MMT in soil at concentrations above 2 ppm. A soil sample is extracted with isooctane
and bromine is added to decompose the MMT. Manganese is then extracted using a
dilute hydrochloric acid solution and quantified by atomic absorption
spectrophotometry (Albemarle Corporation 1976).
Methods have been described for the determination of inorganic Mn in soil, sediments,
and sludge. In general these procedures require acid extraction/digestion prior to
analysis by atomic absorption spectrophotometry or inductivity coupled plasma atomic
emission spectrophotometry (ATSDR 2000).
Priority Existing Chemical Assessment Report Number 24
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7. Importation and Use of MMT
7.1 Importation
MMT is imported only. The manufacture of MMT does not occur in Australia.
Three companies import AVSR products containing MMT into Australia. The products
are imported in bulk as a 62% MMT petroleum distillate solution in 10 000 L isotanks
(HiTEC 3062) and as similar 60 and 62% MMT solutions (Wynn's Octane Booster
Concentrate and TK-660 respectively) in 205L steel drums. Solutions are less
commonly imported in 450 L steel cylinders. Drummed concentrates are blended into
aftermarket fuel additives in 300, 350 or 500 mL plastic bottles. MMT is also imported
in pre-packaged aftermarket fuel additive products in 350 mL plastic bottles.
A total of less than 180 tonnes/year of MMT are imported into Australia with less than
10 tonnes/year imported pre-packaged or for formulation into aftermarket fuel
additives.
7.2 Uses
MMT is a multifunctional fuel additive and is commonly added to internal combustion
engine fuels as a smoke abatement agent, an octane enhancer and inhibitor of valve seat
recession. MMT is also reported to reduce particulate smoke emissions from household,
commercial, industrial, and marine burners. This report only considers the use of MMT
as an AVSR in Australia. MMT is currently not sold in Australia solely as an octane
enhancer.
In LRP, MMT is recommended for use at treat rates of 72.6 mg MMT (18 mg Mn)/L (<
0.01% MMT/L fuel). Aftermarket fuel additives contain MMT at < 10% w/w and at
recommended treat rates, treated fuel will contain MMT at < 150 mg MMT (38 mg
Mn)/L (< 0.02% MMT/L fuel).
7.2.1 Demand for anti-valve seat recession additives
Anti-valve seat recession fuel additives are available for both oil refinery/terminal and
consumer use. AVSR fuel additives may be delivered either by pre-blending to
unleaded petrol at the oil refinery or terminal (LRP) or purchased separately and added
to unleaded petrol by the vehicle owner. The total Australian AVSR additive market
will be referred to as the "LRP market" in this report.
Following the declaration of AVSR fuel additives as a Priority Existing Chemical,
importers and manufacturers of various AVSR fuel additives provided information on
the import/manufacturing quantities and uses of their chemicals for 2000 and 2001.
This information was used to estimate a total LRP market for 2001 of approximately
2500 ML, calculated using AVSR additive treatment doses for LRP and AVSR
import/manufacturing volumes as recommended by AVSR additive manufacturers. The
calculated figure of 2500 ML is slightly higher than the bulk LRP sales volumes for
Methylcyclopentadienyl manganese tricarbonyl (MMT) 13
July 2000 to June 2001 of 1848 ML (Department of Industry, Science and Research,
2001).
The market share of individual AVSR fuel additives in Australia has not been disclosed
in this report due to commercial-in-confidence considerations. An analysis of the
import and manufacturing data demonstrated that the aftermarket application of AVSR
additives in Australia was less than 10 % of the total LRP market in 2001.
In Australia, vehicles requiring leaded petrol are the major consumers of LRP. These
vehicles requiring leaded petrol include passenger vehicles, light commercial trucks,
rigid trucks, articulated trucks, non-freight carrying trucks, buses and motorcycles
(Australian Bureau of Statistics (ABS), 2001). It is likely there are also other VSR
sensitive vehicles requiring AVSR additives, e.g., tractors and some plant and
equipment engines, not included on the Australian Motor Vehicle Census. However,
these vehicles and engines are not expected to represent a significant component of the
AVSR market.
There is a declining Australian market for LRP sales (Australian Institute of Petroleum,
1999) and hence AVSR additives. This is due to attrition from the Australian motor
fleet of vehicles designed to run on leaded petrol (Figure 2).
By 2004, bulk sales of LRP are expected to decline to less than 5 % of total petrol sales
(Australian Petroleum Gazette, 1999). This may render the general provision and sale
of bulk LRP by the oil refineries and terminals uneconomical. Phase-out by the oil
refineries and terminals of the provision of bulk LRP is yet to be announced by the
Australian petroleum industry.
Aftermarket addition of AVSR fuel additives rather than bulk treatment by the oil
refineries and terminals is likely to eventually become, therefore, the only option for
motorists with vehicles designed to run on leaded petrol. This may occur as early as
2004 as the supply of LRP from the oil refineries and terminal diminishes significantly.
Implementation of any partial or total changeover from bulk to aftermarket supply of
LRP would, no doubt, require a broad consensus among stakeholders, entailing
consideration of technical and practical needs of the program and understanding and
acceptance by the public.
7.2.2 Use scenarios
Two use (exposure and emission) scenarios have been assessed in this report ?the
present state of the market, and that likely to occur at 2004. Both scenarios are
considered because of anticipated changes in occupational health and safety, public
health or environmental exposure as a result of a decreasing supply of bulk LRP and the
consequent increasing use of aftermarket AVSR products and also the attrition from the
Australia motor vehicle population of VSR sensitive vehicles. Details of the AVSR
additive use-scenarios are presented in Table 2.
Priority Existing Chemical Assessment Report Number 24
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Table 2. Summary of the AVSR additive use scenarios
Present Use Scenario
Present AVSR additive LRP market: 2 500 ML for 2 500 000 vehicles.
10 % aftermarket: 90 % bulk AVSR additive market.
2004 Scenario
AVSR additive LRP market in 2004: 1 000 ML for 1 000 000 vehicles.
100 % aftermarket AVSR additive market.
The Present Use scenario was based upon import and manufacturing data provided by
industry for the calendar year 2001. The calculation of 2,500,000 vehicles is based
upon 2001 calendar year total AVSR additive import and manufacturing data and a
petrol fill-up rate of 19.4 L/week/leaded vehicle (Appendix 1).
The calculated figure of 2 500 000 vehicles for the Present Use scenario (Table 2) is
slightly lower than the ABS Motor Vehicle Census 31 March 2001 of 2 904 342
vehicles. This is attributed to the inclusion in the ABS data of all leaded vehicles
irrespective of the requirement for or use of an AVSR additive. For example, not all
vehicles requiring leaded petrol are VSR susceptible and require an AVSR additive. In
2000, more than 30 % of cars built before 1986 were estimated to run efficiently on
normal unleaded petrol, with the remaining 70 % requiring an AVSR additive (Hill
2000).
The forecast 1 000 000 vehicles for the 2004 Scenario were derived from Australian
Bureau of Statistics motor vehicle census data (Australian Bureau of Statistics, 1998,
2001). One million VSR susceptible vehicles equates to a demand for LRP of
approximately 1 000 ML in 2004. A description of the calculation for LRP demand in
2004 is also given in Appendix 1. The calculated LRP demand of 1 000 ML in 2004 is
slightly higher than the Australian Institute of Petroleum AIP sales forecast made in
1999 of nil to 800 ML (Australian Petroleum Gazette, 1999).
In 2010, a remaining niche market of VSR-sensitive older vehicles and engines
requiring leaded petrol is expected (National Heritage Trust, 2000).
For the purposes of commercial-in-confidence and changes in market share, it has been
assumed that only one AVSR additive has 100 % market share in each use scenario.
Across the assessments of all AVSR additives, the same bulk to aftermarket share is
assumed for each AVSR additive.
Methylcyclopentadienyl manganese tricarbonyl (MMT) 15
Figure 2. The Number of Vehicles Requiring Leaded or Lead-Replacement Petrol
Leaded Vehicle Population, Census Year
Leaded Vehicle Numbers (million
6
5
4
3
2
1
0
1994 1996 1998 2000 2002 2004
Motor Vehicle Census Year (ABS)
() 1995-2000
(--) 2001-2004 (Forecast)
(Australian Bureau of Statistics, 1998, 2001)
Priority Existing Chemical Assessment Report Number 24
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8. Exposure
The use of MMT as an AVSR agent additive for use in LRP involves relatively small
releases of the compound to the environment (details in Section 8.1.2). In general, these
releases are of a very diffuse nature since the motor fuel is used throughout Australia.
Further, the compound is susceptible to abiotic (physico-chemical) degradation
mechanisms, particularly through indirect photolysis, and consequently the MMT
released to the environment is not expected to be persistent where sunlight is prevalent.
However, leakages from underground fuel storage tanks (UST) where LRP is stored
provide a potential process for point source releases of MMT into soils and
groundwater and potentially other environmental media (eg. surface waters, air). In
these environments, MMT may be persistent and may not readily degrade since
photolysis is the main degradation route.
Most of the MMT is destroyed in the cylinders and exhaust trains of motors with
production of a variety of inorganic salts and oxides of Mn. A proportion of this
inorganic material is released to the atmosphere from the exhaust systems in association
with small particles in the respirable size range. Certain adverse human health effects
may be associated with inhaled Mn compounds (Davis, 1999; IPCS, 1999) and so the
nature of the emitted particles is of importance.
The emissions of exhaust gases such as unburnt hydrocarbons, oxides of nitrogen and
particulate material are also pertinent to the overall environmental effect of fuel
combustion, and available data on the influence of MMT on these exhaust emissions is
briefly reviewed.
8.1 Environmental exposure
Based on the current total AVSR additive LRP market (see Section 7) and assuming a
dose rate of 72.6 mg/L of MMT, the amount of MMT in this market in Australia is
expected to be less than 180 tonnes per year. The majority of this importation is for
formulation of LRP. Imports of MMT solutions for aftermarket use are less than 10
tonnes per year.
8.1.1 Use of MMT as an AVSR Agent
Most of the MMT used in Australia will be imported in 10 000 L isotanks as a 62%
solution in a mixed hydrocarbon solvent (HiTEC 3062) for blending into LRP at
refineries. Significantly smaller quantities will be imported as solutions intended for
formulation into aftermarket additives to be used as fuel supplements by individual
vehicle owners. Small volumes of MMT are imported as pre-packaged additives.
The bulk HiTEC 3062 imported in isotanks will be transported to petrol refineries
where metered quantities of HiTEC 3062 will be blended into fuel to give a final
concentration of MMT of around 72.6 mg/L which corresponds to approximately 18
mg/L Mn.
Methylcyclopentadienyl manganese tricarbonyl (MMT) 17
Since the addition of AVSR agents is only required in LRP for older petrol vehicles that
are expected to be progressively retired, the use of LRP is expected to decrease with a
concomitant decrease in MMT usage.
8.1.2 Release of MMT
At petrol refineries, all pumping and metering of the MMT into blending tanks is
conducted under automatic control. Isotanks, other storage tanks and pumping/control
equipment associated with the transfer of the MMT solutions are installed in bunded
areas to contain all leaks or spills. Due to these engineering controls very little release
of MMT during routine blending operations is expected, and while the applicants
provided no information on likely releases, previous experience in assessing other fuel
additives suggest that these losses are unlikely to exceed 0.1% of the HiTEC 3062.
Based on an annual import of 180 tonnes of MMT, and assuming all this is used at the
refineries, an anticipated maximum annual release of no more than 180 kg would be
apportioned between those fuel refineries producing LRP.
Any spillage resulting from the transfer activities would most likely be diverted to on
site waste treatment plants where the organic materials would be recovered into a
sludge which would be incinerated or possibly be placed into a landfill.
Spillage of petrol during transfer from the tanker trucks to underground storage at
consumer petrol outlets or from bowsers to consumer vehicles would also result in
small releases. While no definitive data were supplied, previous experience in the
assessment of fuel additives indicates that losses are not expected to amount to more
than 0.5% of petrol volume, equating to an (estimated maximum) annual release of
around 900 kg.
Like other fuels, LRP is typically stored in underground storage tanks (USTs). USTs
have a tendency to begin leaking over time, resulting in release of fuel to groundwater.
USTs have been installed throughout Australia at terminals and refineries, fuel depots,
service stations, and many private facilities and organisations have USTs for fuel
storage.
Not all USTs leak, and not all leaks pose an unacceptable risk to the environment.
However, many have and have required decommissioning and land remediation. The
length of service of the tank is one of a number of factors increasing the risk of UST
leakage. Other factors include the type of construction materials, presence of liners, fuel
type, fittings/pipes and environmental conditions surrounding the UST. Major fuel
suppliers generally have tank decommissioning and replacement programs and install
leak detection equipment on their tanks to prevent leaks from occurring and to trigger
pollution abatement procedures to minimise risks to the environment where leaks are
detected.
A relatively small quantity of MMT is imported in 205 L drums for formulation into
after market fuel additives containing < 10% w/w MMT. This will be sold through
consumer outlets in plastic bottles up to 500 mL capacity to be added to the fuel in the
vehicle tanks by the owners. While losses of MMT through formulation into the
aftermarket products are expected to be small (not exceeding 0.1%), the use patterns of
these products and the small package sizes indicate higher release rates from spillage
and remnants of additive left in the bottles. No information on this issue was provided,
but it is not unreasonable to assume that up to 5% of the formulation could be spilt or
be left in the bottles after the majority of the contents has been added to the fuel,
Priority Existing Chemical Assessment Report Number 24
18
equating to an annual release of approximately 500 kg. The emptied bottles are
expected to be placed into landfill and due to the Australia-wide use of these additives,
the associated release of MMT from disposal of the emptied bottles overall will be
diffuse and at low levels.
All emptied isotanks used for importing the bulk HiTEC 3062 into Australia will be
returned to the USA for refurbishment and refilling, so there will be no local release of
residuals remaining in empty bulk shipment containers. Drums containing MMT for
formulation of aftermarket additives are cleaned at drum recycling facilities and any
residual MMT becomes incorporated into waste sludge. This is either placed into
landfill or incinerated.
MMT has a much lower vapour pressure at 0.01 kPa (at 20癈) compared with
approximately 70 kPa for the hydrocarbon constituents of petrol (Environment
Australia, 2000). Consequently, spilt MMT is likely to be left on the concrete aprons of
service stations following evaporation of the more volatile fuel components, and while
it is possible that this residual MMT could be washed from the concrete aprons into
stormwater drains or onto surrounding soil, the compound is not stable to light (Section
9.2.1), and in reality very little is expected to enter the water or soil compartments. In
any case, since use of the petrol is expected to be nationwide these releases will be very
diffuse and at low concentrations.
Experimental data indicate that at least 99.5% of the MMT present in the fuel is
destroyed during combustion with a maximum of 0.5% of unconverted compound
emitted with exhaust gases (Ter Haar et al., 1975). Assuming imports of 180 tonnes of
MMT per annum, this equates to an annual release of 900 kg to the atmosphere, again
in a very diffuse manner and at low concentrations. Due to rapid degradation of MMT
through direct photolysis and/or reaction with atmospheric hydroxyl radicals (Section
8.2.1) the atmospheric concentration of un-degraded MMT is expected to be negligible.
Some MMT may enter the atmospheric compartment through evaporation from fuel,
but measurements of the concentration in air in the vicinity of filling stations suggest
that these amounts are very small (Zayed et al., 1999a).
Overall, the blending of HiTEC 3062 into LRP and the transfer of fuel to consumer
vehicles are expected to release a maximum of around 2000 kg/year of MMT, with
about half this becoming associated with soil or possibly stormwater. However, this
release will be nationwide and at low concentrations and the sensitivity of the
compound to light and other degradation mechanisms precludes environmental
persistence. The remainder would be released to the atmosphere and is expected to
rapidly degrade.
8.1.3 Exhaust release of manganese compounds from combustion of MMT
Most of the MMT used each year will be destroyed during combustion in the engine
cylinders, and recent data indicate that the Mn component is converted to a mixture of
Mn oxides (e.g. Mn3O4) and salts such as Mn phosphate (Mn3[PO4]2) and Mn sulphate
(MnSO4) ?see for example Colmenares et al. (1999) and Ressler et al. (2000). A
proportion of these inorganic derivatives are released in association with particulate
material in the exhaust emissions. The chemical nature and physical form in which
these Mn-containing decomposition products are released in engine exhaust gases is of
importance and will be discussed in further detail in following subsections.
Methylcyclopentadienyl manganese tricarbonyl (MMT) 19
8.1.4 Emission rate and physical form of manganese in exhaust gases
Emission rates
While it could be expected that almost all the Mn added to the fuel would be emitted in
the exhaust gases, recent monitoring of the Mn levels in vehicle exhaust gases suggests
that this is not the case, with only part of the fuel Mn manifesting itself in the tailpipe
emissions (Ardeleanu et al., 1999; Roos et al., 2000). The actual proportion of Mn
emitted is very variable and appears to depend on various factors including the overall
distance that the vehicle has been driven using MMT supplemented fuel. Also, for a
given vehicle, the Mn emission rate is particularly sensitive to the driving conditions ?br>
for example urban versus highway driving (Ardeleanu et al., 1999). In dynamometer
tests on 8 different vehicles which had previously been driven using MMT
supplemented fuel between 3 700 km and 124 000 km, and then "driven" for the
equivalent of approximately 17 km on the dynamometer equipment, Ardeleanu et al.
(1999) determined Mn emission rates of between 4 and 41%. In all cases, more Mn was
emitted when the vehicle was run under the conditions of an urban driving cycle (i.e.
stop, idle and start) compared to highway driving conditions. When averaged over all
vehicles, with each vehicle "driven" for approximately 17 miles (27.4 km) under each
driving regime (i.e. urban and highway), the mean Mn emission rate was around 12.3%.
However, there was a positive correlation between the rate of Mn emission and the
overall length of service of the vehicles, with those cars that had accumulated the
highest driving time prior to the test emitting higher exhaust concentrations of Mn. This
correlation was stronger for the data collected during the urban driving cycle than the
highway cycle.
Experimental determination of Mn exhaust emissions have been reported by other
authors with emission rates determined between 6 and 45%. These earlier results have
been summarised in the paper by Ardeleanu et al. (1999) and are in general agreement
with the results of their own study. A second recent study also comprehensively
summarised emission data from a number of tests using a variety of test vehicles with
4-8 cylinder motors, and concluded that the proportion of Mn emitted under open road
(highway) conditions is 6-8% of the Mn contained in the MMT compared with 12-16%
emitted during urban driving, with these results showing no dependence on motor size
or type (Roos et al., 2000). This study also reported results from Lynam et al (1994)
that approximately 27% of the Mn in the fuel of three light duty trucks was emitted in
the exhaust after an accumulated 20,000 mile (32,000 km) urban driving test.
It should be noted that all these data indicate that Mn emissions from vehicle exhausts
(with concomitant exposure potential through particulate inhalation) are expected to be
significantly higher in areas of high traffic density where the vehicles are undergoing
alternate periods of acceleration and braking ?i.e. typically under conditions of urban
driving during business hours.
The balance of the Mn introduced in the fuel (approximately 87.7%) is apparently
accumulated in the engines or the exhaust systems of the vehicles (Ardeleanu et al.,
1999). Similar conclusions were reached by Roos et al. (2000). While no details of this
were discussed, the authors also indicated that some of the Mn becomes associated with
the engine lubricating oil.
The work by Ardeleanu et al., (1999) appears to have been well designed and executed,
and the average Mn exhaust emission figure of 12.3% of fuel Mn (as MMT) derived in
Priority Existing Chemical Assessment Report Number 24
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this work appears to be an appropriate emission figure. However, this may
underestimate the Mn emission rate from particular vehicles under certain driving
conditions, and due to the considerable spread in the available emission data (i.e. 4-
41%), a figure of 20% will be used in the present report when estimating likely Mn
emissions from vehicles using MMT supplemented fuel within Australia.
Since it is anticipated that annually around 180 tonnes of MMT (containing
approximately 45.4 tonnes of Mn) may be used in petrol as an AVSR agent within
Australia, and assuming 20% of the Mn is released in exhaust emissions, this equates to
an annual release of approximately 9.1 tonnes of Mn to the atmosphere. These
emissions will be in the form of inorganic Mn compounds associated with fine
particulate matter, and while this release will be diffuse, higher atmospheric
concentrations of the emitted particulates are expected in urban areas where traffic
density is high.
Nature of particulate emissions in vehicle exhaust streams
The Mn released in exhaust emissions appears to be primarily associated with small
particles composed of soot and unburnt hydrocarbons. It is recognised that most of the
Mn is associated with particles of respirable size (< 2.5 祄), and in a recent study the
distribution of Mn through the size fractions of exhaust particulate emissions was
determined over the 0.056 to 3.1 祄 size range (Roos et al., 2000). The exhaust
particulate emissions from eight vehicles which had been subjected to the standard
urban driving test regime over the equivalent of 40 000 miles (64 000 km) were
collected and on average it was found that approximately 80% of the emitted Mn was
associated within particles of diameter < 1.8 祄, with a peak in the 0.32-1.8 祄 range
which accounted for roughly 40% of the Mn.
The particle size distribution in engine exhausts from a number of vehicles was also
determined using Scanning Electron Microscopy (SEM) to count the actual particle
frequency in particular size ranges (Ardeleanu et al., 1999). This study found that more
than 96% of the particulate matter was in the < 2.5 祄 range with 86% having
diameters < 1 祄 and 39.2% having diameters < 0.5 祄. In an associated paper it was
found that SEM studies indicated that the Mn-containing particles are amorphous, and
the chemical forms of the Mn compounds present were also characterised (Zayed et al.,
1999b). Another recent study also determined that 80-90% of the Mn emitted from
vehicle exhausts was associated with particles < 2.5 祄 (Colmenares et al., 1999).
Chemical speciation of emitted manganese
In early work on this topic, it was considered that all the Mn emitted in vehicle exhaust
streams was in the form of oxides, primarily Mn3O4 (Ter Haar et al., 1975). This
conclusion was reached apparently on the basis of X-ray diffraction data alone, and
although no experimental details were given in the paper, the assertion that Mn3O4 is
the major emitted product has since often been made in the literature, e.g. Abbott
(1987).
However, a number of recent studies using sophisticated X-ray spectroscopy and other
spectroscopic techniques have shown that while Mn3O4 is a minor component of
exhaust emissions, most of the emitted Mn is in the form of Mn phosphate ?either
Mn3(PO4)2 or possibly Mn5(PO4)2(H2PO4)2 ?and Mn sulphate - MnSO4. It is important
to note that the oxidation state of the Mn in the exhaust emissions is essentially +2, with
only the small amount of Mn3O4 having some Mn in higher oxidation states.
Methylcyclopentadienyl manganese tricarbonyl (MMT) 21
Electron spectroscopy together with L-edge X-ray absorption spectroscopy was used in
an analysis of the Mn-containing particulate matter in motor vehicle exhausts, and it
was concluded that Mn phosphates and Mn sulphate are the major Mn compounds
present (Colmenares et al., 1999). Interestingly, these authors stated that Mn phosphate
is the primary combustion product formed in the cylinders since these compounds have
very high thermal stability, but as the exhaust gases cool some of this is converted to
Mn sulphate ?presumably through reaction with SO2. In a separate study it was also
found that Mn phosphates and Mn sulphate were the major Mn compounds present in
the exhaust particulates with some Mn3O4 (Ressler et al 2000). The percentage of
emitted Mn was 42.4% as Mn phosphate, 35.5% as Mn sulphate with the remainder
(22.1%) as Mn3O4. Another study also found that the primary Mn species in exhaust
particulates was a manganous phosphate together with some manganous sulphate
(Zayed et al., 1999b). In an associated paper the authors also make the point that most
of the Mn in the exhaust particles is water soluble (Ardeleanu et al., 1999). The
presence of Mn sulphate, phosphate and oxide in exhaust emissions of vehicles fuelled
with MMT containing petrol has also been confirmed in a more recent study using Mn
K edge X-ray adsorption techniques (Molders et al., 2000).
In many of these studies on Mn speciation the source of the phosphorus was stated as
being from zinc dialkyl dithiophosphate, which is a minor component of some
lubricating oils (Colmenares et al., 1999, Ressler et al., 2000 and Molders et al., 2001).
8.1.5 Effect of MMT on exhaust gases (NOx, CO, CO2, hydrocarbons,
particulates) and onboard pollution control equipment
There have been several studies conducted to evaluate the impact of MMT in fuel on
exhaust gases, and there remains a dispute at this point in time as to the effect of MMT
on vehicle exhaust gases and fuel efficiency.
In an extensive comparative test of the exhaust gas emissions from 24 vehicles (3
examples of 8 different 1987 models) fuelled with petrol containing MMT at a level of
8.27 mg Mn/L, Lenane et al. (1994) found lower nitrogen oxides (NOx) and carbon
monoxide (CO) emissions in the exhaust gases of these vehicles than in the emissions
from a fleet of 24 similar vehicles fuelled with the baseline petrol alone. Each vehicle
was run over a 75 000-mile (121 000 km) course according to a test protocol based on a
USEPA test procedure, and exhaust emissions for hydrocarbons, NOx and CO were
determined for each vehicle throughout the test. In total some 2500 emission tests were
conducted, almost all of which were used in the subsequent analysis. The results
averaged over the 121 000 km course are summarised in Table 3 and strongly indicate
that the emissions of NOx and CO were significantly less for those vehicles fuelled
with the petrol containing MMT, with reductions of up to 20% for NOx and around 6%
for CO. However, the hydrocarbon emissions were approximately 6% higher in the
emissions from the MMT supplemented vehicles, than for those running on the base
petrol and once established (over the first 4000 miles of the test) this increase appeared
to be fairly constant over the test duration. No further discussion on this result was
offered in the paper.
Priority Existing Chemical Assessment Report Number 24
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Table 3. Emission data for MMT use (Lenane et al., 1994)
MMT Base Petrol % Change of MMT
(8.27 mg Mn/L) Fuelled Vehicles Relative
to Base Petrol Fuelled
Vehicles
NOx Emissions 0.43 (g/mile) 0.55 (g/mile) - 20%
CO Emissions 3.08 (g/mile) 3.30 (g/mile) -6%
Hydrocarbon 0.307 (g/mile) 0.289 (g/mile) +6%
Emissions
In another paper the authors describe the results of an extensive fleet test in which more
than 100 vehicles accumulated over 8.5 million kilometres, and where monitoring of
the exhaust emissions showed that the presence of MMT in the fuel (8.27 mg Mn/L)
leads to an average reduction of 20% in NOx emissions and 5-6% reduction in CO
emissions, which are similar to the results above (Roos et al., 1994). This study appears
to be an extension of that discussed by Lenane et al. (1994).
In another recent publication the authors also indicate decreased emissions of
hydrocarbons, NOx, CO and benzene from a vehicle fuelled with a "low aromatic"
petrol containing MMT (equivalent to 18 mg/L Mn) compared with those from when
the vehicle was fuelled with a base petrol which contained 3% more aromatics in order
to give the fuel the same octane rating (Hollrah and Roos, 2000). While the bar charts
presented in this paper indicated definite reductions in pollutant emissions from the
MMT fuel, no actual figures were given. However, in respect of this, the lower
emissions of hydrocarbons and benzenes can be directly attributable to the lower
aromatic content of the MMT-containing fuel.
A very recent study released by the Alliance of Automobile Manufacturers, the
Association of International Automobile Manufacturers and the Canadian Vehicle
Manufacturer's Association of the effects of MMT on vehicle emissions (Alliance of
Automobile Manufacturers; AAM, 2002) purports to show different results to those
above. Vehicles were powered either with regular grade unleaded gasoline or similar
gasoline plus MMT at a treat rate of 8.3 mg/L. Emissions were sampled directly from
the engine via an engine-out sample tap and also at the tailpipe after exhaust system
emissions control. This study reports increased emissions from MMT use (Table 4).
Table 4. Emission data for MMT use (AAM, 2002)
% Change of MMT Fuelled Vehicles
Relative to Base Petrol Fuelled Vehicles
NOx Emissions Engine-out +1%
Tailpipe ?0%
CO Emissions Engine-out +1%
Tailpipe +6%
1%
CO2 Emissions
Hydrocarbon Emissions Engine-out +14%
Tailpipe +13%
However, the above results of AAM (2002) themselves are the subject of subsequent
critique (Roos et al, 2002a; Roos et al, 2002b). These disparate findings indicate
Methylcyclopentadienyl manganese tricarbonyl (MMT) 23
ongoing uncertainty regarding the actual effects of MMT on vehicle exhaust emission
quality.
8.2 Fate
Although it is expected that little MMT will be released into the environment from its
use as a fuel additive (Section 8.1.2) there are a number of relevant papers in the
literature addressing the environmental fate of this compound, and these are briefly
summarised in the following subsections. As indicated previously, most of the MMT
will be destroyed during combustion of the fuel with release of inorganic Mn
compounds (Mn phosphates, sulphates and oxides), with almost all the released Mn
being associated with and incorporated in small particles.
8.2.1 Atmosphere
MMT is unstable to photochemical degradation in the atmosphere, with a reported
atmospheric half-life of 8-18 seconds determined from direct measurement of the
content of organic and inorganic Mn (apparently Mn oxides and Mn carbonates) down
wind of a device designed to release MMT at a controlled rate (Ter Haar et al., 1975).
However, the authors indicated that experimental uncertainties precluded a more
precise determination, and while they endeavoured to obtain more accurate
measurements through direct photolysis of an MMT/air mixture in a quartz tube under
well-controlled conditions, this effort was confounded by deposition of photolysis
products on the surface of the tube. Nevertheless, the conclusion from these
experiments was that MMT decomposes quickly in the atmosphere and the
decomposition mechanism was reported to involve both light (wavelength 340-440 nm)
and atmospheric oxygen. However, a more recent study indicated that the first step in
the degradation process involves adsorption of a visible-UV photon, which then
weakens the bonds between Mn and the CO groups leading to ejection of a CO
molecule (Vreugdenhil and Butler, 1998). Regardless of the detailed mechanism for
photo-degradation, the ultimate degradation products would most likely be water, CO2
and MnO2.
A recent study determined the rate constant for reaction of atmospheric MMT for direct
photolysis (with visible-UV light), with hydroxyl radicals and with ozone, and found
these to be (1.3?.1) x 10-2, (1.1?.3) x 10-10 and 7.7?.9 x 10-18 cm3 molecule-1 sec-1
respectively. These rate constants provided half-lives of 80 sec, 1.3-2.5 hours and 14-72
hours for photolysis, reaction with OH radicals and ozone respectively (Wallington et
al., 1999).
8.2.2 Water
In a determination of the ready biodegradation of MMT in a closed bottle test, while
46% degradation was observed after 15 days, no further degradation was observed after
this time (Analytical Biochemistry Laboratories Inc., 1990). The test was conducted
according to the protocols of OECD TG 301 D by incubating samples of the MMT
(equivalent to 2 mg/L carbon) with sewage bacteria, and monitoring the residual
biochemical oxygen demand (BOD) after 5, 15 and 28 days. The result of this test
indicates that the compound cannot be classified as readily biodegradable.
The rate of photolytic decomposition of MMT in distilled water was determined and
found to be characterised by a half-life of approximately 1 minute when a solution of
Priority Existing Chemical Assessment Report Number 24
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the compound was exposed to midday sunlight (Garrison et al., 1995). The authors
remarked that this was similar to the result obtained by Ter Haar et al. for direct
atmospheric photolysis. A separate part of this study also examined the possibility of
degradation of MMT (in the dark) by direct hydrolysis, and found that this process was
very slow if indeed it happens at all, with an estimated minimum half-life (at 25?2癈)
of 500 days (Garrison et al., 1995).
It is also of interest that these authors (Garrison et al., 1995) indicated that literature
values for water solubility and the n-octanol/water partition coefficient were uncertain.
Since these two physico-chemical parameters are important for the determination of
environmental fate, these authors presented their own measured values and determined
the water solubility at 25癈 as 29? mg/L and Log Kow as 3.7 (again at 25癈). This
water solubility together with the vapour pressure of MMT (1.1x10-2 kPa at 25癈 -
Ethyl Corporation) were used to calculate the Henrys Law Constant as 82 Pa.m3.mol-1,
indicating that any MMT entering the water compartment (and not degraded through
photolysis) would evaporate and would be destroyed through photolysis in the
atmosphere (Lyman, Rheel and Rosenblatt, 1990).
8.2.3 Soils and sediments
The relatively large value for Log Kow (3.7) indicates that MMT would have significant
affinity for the organic component of soils and sediments, although the water solubility
(29 mg/L) could bestow some mobility to any MMT that enters the soil/sediment
compartment. However, in an investigation of the adsorption of MMT to a variety of
soil types as well as to the important soil minerals alumina and silica, Vreugdenhil and
Butler (1998) found that MMT binds to soils. The mechanism appears to be due to
interaction of the carbonyl groups of MMT with silica or alumina surfaces of clay
minerals rather than through association of the compound with the organic component
of the soils. These authors concluded that MMT can adsorb to and become immobilised
in soils and that this would reduce its potential for photo-degradation.
Degradation of MMT spiked into a natural anaerobic aqueous sediment was also
studied by Garrison et al. (1995), and although the sediment was kept in the dark to
prevent photolytic degradation, no measures were taken to either encourage or hinder
biodegradation. In this experiment, the rate of disappearance of the MMT was very
slow with data fitted to first order kinetics providing a degradation half-life of 0.5-1.5
years (Garrison et al., 1995).
8.2.4 Fate of inorganic compounds from combustion of MMT
Most of the MMT used as an AVSR in fuel within Australia will be combusted and as
described above will be converted to inorganic Mn compounds (oxides, sulphate and
phosphate), most of which apparently remain in the exhaust train. However, around
20% of these Mn compounds (approximately 9.1 tonnes) could be expected to be
emitted with exhaust gases associated with very fine particles (< 2.5 祄). These small
particles have very low quiescent air sedimentation velocities of around 1-2 cm/hour
and less, and are consequently not expected to settle under gravity prior to being
precipitated.
For example, the settling velocity of the particles in non-turbulent air can be estimated
using Stokes law (CRC, 1977), which gives the settling velocity for a particle of radius
r (cm) as:
Methylcyclopentadienyl manganese tricarbonyl (MMT) 25
Vset = 2gr2d/9
where g is the acceleration of gravity, d is the density of the particle (gm/cm3) and is
the viscosity of air, which is around 180 x 10-6 gm/cm-sec at 25癈. Taking r as 1.5 祄
(= 1.5 x 10-4 cm), and assuming d is 2gm/cm3, Vset is calculated as 3.75 x 10-4 cm/sec
(= 1.35 cm/h).
Consequently, the small particles emitted from the exhaust pipes are expected to remain
suspended in the air for prolonged periods.
Ultimately these fine particles would be precipitated to the ground with rain or through
becoming associated with larger particles with higher sedimentation velocities, and
would become associated with soils and aquatic sediments. The inorganic Mn residues
remaining in the engines and exhaust systems of vehicles would ultimately be placed
into landfill with discarded cars and exhaust systems, or if these are recycled for metal
recovery, the residues would become associated with slag and other products from the
blast furnaces.
8.3 Environmental concentrations of MMT and manganese
8.3.1 MMT
The atmospheric concentration of MMT is expected to be very low due to the diffuse
nature of the releases and the rapid photochemical decomposition of the compound.
Recent data support this conclusion, and in a monitoring program in Montreal a mean
atmospheric MMT concentration of only 5 ng/m3 was determined compared with a
mean total atmospheric Mn concentration of 103 ng/m3 ?see Section 8.3.2 ?(Zayed et
al., 1999a).
Although the chemical may be persistent in soils and sediments, except in the cases of
gross spillage of HiTEC 3062 or petrol containing the chemical (eg. leakage from USTs
or aboveground spillages), very little release to this compartment is likely and apart
from areas in the vicinity of such spills and leaks no accumulation of MMT is likely in
soils and groundwater.
In the immediate vicinity of leaking USTs, and at LRP spill sites, the MMT
concentration may approximate that of MMT in LRP (eg. 72.6 mg/L). Site-specific
conditions will determine the environmental concentration of MMT in groundwater
with distance away from leaking UST sources. In groundwater, MMT is likely to be
relatively persistent and its water solubility indicates it may be mobile in groundwater.
8.3.2 Manganese in the atmosphere in Canada
The most significant effect from the use of MMT in petrol is the generation and release
of small respirable particles (< 2.5 祄 in diameter) containing inorganic Mn, most of
which is expected to be in the +2 oxidation state. Canada has been using MMT as a
replacement for tetraethyl lead in fuel since 1976 and it may be expected that in general
(i.e. not in the vicinity of steel works, battery factories or other possible point sources
of Mn) atmospheric Mn could originate from combustion of MMT.
Several studies measuring atmospheric concentrations of Mn have been conducted in
Canada. In a study of combustion products from MMT use is gasoline, Wood and
Priority Existing Chemical Assessment Report Number 24
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Egyed (1994) published ambient air Mn PM10 and PM2.5 concentrations for a range of
Canadian cities for 1986-1992 from data from the Environment Canada National Air
Pollution Surveillance and the Ontario Ministry of the Environment and Energy air-
monitoring network. Generally, levels of approximately 5-50 ng/m3 were recorded with
most cities having ambient air PM2.5 concentrations in the range of 10-20 ng/m3.
Unsurprisingly, the highest levels were measured in cities with identifiable Mn emitting
industries.
Loranger and Zayed (1997) measured the average air concentration of respirable Mn
(PM5) in two urban sites in Montreal. Levels measured in a low traffic area (botanical
gardens) were approximately 15 ng/m3 whilst at a high traffic area (waterworks) levels
were approximately 24 ng/m3.
An exposure assessment of airborne Mn was conducted in Toronto from June 1995 to
September 1996 by Pellizzari et al (1999) and further analysed by Crump (2000). In
this study, personal exposure levels and static residential indoor and outdoor and
ambient levels at fixed sites were measured. The mean concentration of PM2.5 Mn
measured at a ground level residential outdoors site was 9.7 ng/m3. Levels measured at
two other outdoor sites, one at ground level and one on the roof of a 4 storey building
downwind from a major freeway averaged 17.1 and 11.4 ng/m3 respectively. In
contrast, PM2.5 levels measured indoors at residential sites were lower with an average
of 5.5 ng/m3 (Crump 2000).
Another recent Canadian study determined the atmospheric concentrations of total Mn
(MnT), respirable Mn (MnR) and MMT itself in five urban microenvironments in
Montreal (Zayed et al., 1999a). In this study, the respirable Mn was taken as the Mn
associated with particles with diameter < 5 祄, and measurements were made at a
petrol station, an underground car park, the centre of Montreal, the vicinity of an
expressway and the vicinity of an oil refinery. The results of a 36-hour sampling
campaign (12 hours for each of three consecutive days) are summarised in Table 5. As
indicated in Table 5, the figures for total atmospheric Mn at different
microenvironments in Montreal are all of similar magnitude, with the petrol station site
showing the highest air MMT levels.
Table 5. Outdoor monitoring levels of microenvironmental Mn and MMT in
Montreal, Canada (Zayed et al; 1999a)
Manganese concentrations (ng/m3)
Sampling Location
MnT MnR MMT
Petrol station 141 35 12
Mid city 103 44 7
Expressway vicinity 127 53 6
Refinery vicinity 66 18 2
Underground car park 78 30 0.4
MEAN 103 36 5
MnT = total atmospheric Mn;
MnR = respirable atmospheric Mn associated with particles with aerodynamic diameter < 5 祄.
Data have been collected between 1981 and 1996 for 10 cities in Ontario (Ontario
Ministry of Environment and Energy, undated, cited in Roos et al., 2000). As an
example of these data, the annual geometric mean total atmospheric Mn levels in
Methylcyclopentadienyl manganese tricarbonyl (MMT) 27
Toronto had a minimum of 24 ng/m3 (1982, 1986) and a maximum of 44 ng/m3 in
1990. Interestingly, the data for all 10 cities showed a steady increase in average
atmospheric Mn levels from 1981 to 1990, and then a gradual decline in subsequent
years.
8.3.3 Manganese in the atmosphere in Australia
Data are available for Mn content of atmospheric particulates for several Australian
capital cities. In contrast to the Canadian data, recent surveys of the nature and
chemical composition of atmospheric particles in 6 cities (Adelaide, Brisbane,
Canberra, Launceston, Melbourne and Sydney) show much lower ambient Mn
concentrations (Ayers et al., 1999). Except for Launceston, the Australian atmospheric
Mn concentrations are roughly one third to one fifth of MnT and MnR levels measured
in Montreal or PM2.5 levels measured outdoors in Toronto. The relevant Australian data
are summarised in Table 6.
Table 6. Mn content of particulate matter (PM) in the atmosphere of Australian
cities (Ayers et al., 1999)
Mn in PM10 (ng/m3) Mn in PM2.5 (ng/m3)
CITY (Sampling period)
10 ?2.4 3.3 ?2.0
Adelaide (August, 1997)
7? 3?
Brisbane (Sept., Oct., Nov. 1996)
5.5 ?3.3 0.6 ?0.9
Canberra (May 1997)
79 ?102 24 ?28
Launceston (June, July 1997)
12 ?1.7 3.3 ?2.3
Melbourne (April 1997)
13 ?11 3.0 ?3.3
Sydney (August 1996)
In the above Australian data, the Mn determinations were for composite samples taken
each day of sampling. The results tabulated are the mean and standard deviations of the
individual daily Mn determinations. Samplers were operated on a 6-day cycle (ie. 24
hour samples taken each 6th day) over approximately a one to two month period in each
city. In total, five 24 hour samples were taken for Sydney, Melbourne, Canberra and
Adelaide and 8 samples for Brisbane and Launceston.
The Launceston Mn data are higher than for the other cities monitored. Whilst a large
manganese-alloy smelter is located approximately 50 km to the northwest of
Launceston, the contribution of this industry to Mn levels in Launceston is not known.
Both the mean and standard deviation results are greater than those for other cities
suggesting elevated atmospheric Mn levels only at certain periods.
It is also relevant to note that in general, most of the detected Mn is associated with the
PM10 fraction. Since MMT was apparently not used in Australian petrol during the
period of this study, the origin of the particulate Mn is probably in terrestrial dust.
Although these data were collected over only one to two months in each city, in the
absence of more comprehensive data the results may be used as a baseline reference set
for any future monitoring of atmospheric Mn levels in Australia after introduction of
MMT. However, there are some much more extensive published data on the nature and
composition of airborne particulate matter in Sydney collected bi-weekly over the 7-
year period January 1992 and December 1998 (Cohen, 1999). These data indicated the
ambient particle-associated Mn concentration as 10 ?15 ng/m3 at Mascot in Sydney,
with the Mn comprising approximately 0.1% of the weight of the particulate matter.
Priority Existing Chemical Assessment Report Number 24
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The level of atmospheric Mn resulting from emissions of Mn from the combustion of
MMT-treated fuel obviously depends on the extent of fuel usage as well as
meteorological conditions in the areas where the fuel is used. There are uncertainties
associated with both these factors and in order to make some estimates of the likely
level of atmospheric Mn resulting from future use of MMT in Australian fuel, it is
necessary to make some assumptions based on the following considerations.
All estimates are made for Sydney with a population of 3 800 000, which comprises
20% of the total Australian population (19 000 000), and covers an area of
approximately 1550 square kilometres. Two scenarios (see Section 7) are examined
corresponding to:
Present use:
Where the total Australian import volume of MMT is constant at 180 tonnes per
annum and this is added to petrol for use as an AVSR agent in lead replacement
petrol, and
2004:
Where the import volume is reduced to 72.6 tonnes per annum to reflect the
expected decreased demand for LRP (and hence for MMT as an AVSR agent) as
the older vehicles are retired.
Since it is reasonable to assume that fuel use would roughly reflect population density,
it will be assumed that 20% of all petrol in Australia would be used in Sydney.
An atmospheric box model approach has been used to estimate Mn air concentrations in
MMT use areas. Implicit in the box model approach is that emissions are expected to
behave as if they are released into a box with horizontal dimensions of the urban area
(selected so that there is no significant influx of emissions into the box). Various
assumptions can then be made about Mn accumulation and dispersion of Mn from the
atmospheric box.
Two predicted environmental exposure concentrations for Mn in the air have been
estimated resulting from the future use of MMT in Australian fuel. These include an
average (AVE) estimate and a reasonable maximum exposure (RME) estimate.
For the calculation of the AVE air Mn concentration representing a long-term average
exposure concentration, total yearly MMT use is used to calculate Mn emissions over
each day with assumed daily clearance of accumulated air Mn from the atmospheric
box.
The RME calculation represents the Mn concentration that may potentially accumulate
in the air during weather period of consecutive windless days. This concentration is
unlikely to be attained frequently. Information on consecutive windless days in
Australian cities is not readily available as this is not a parameter normally monitored.
As such, a conservative estimate of 3 consecutive windless days has been used in this
assessment.
Methylcyclopentadienyl manganese tricarbonyl (MMT) 29
Present use scenario
RME Concentration for Mn
It is estimated that the LRP market for 2001 was 2500 ML (see Section 7). Assuming
MMT has 100% market share and is dosed at a rate of 72.6 mg/L, this equates to an
importation of 180 tonnes per annum of MMT. If 20% of this were to be used in
Sydney, this is equivalent to approximately 500 ML of MMT-treated LRP containing
approximately 36 tonnes of MMT (9.1 tonnes of Mn). Combustion of the MMT will
lead to formation of Mn sulphate, phosphate and oxide containing this Mn. Although
most of these Mn compounds are expected to remain in the vehicle exhaust systems, it
is likely that up to 20% would be released (see section on emission rates in 8.1.4.1),
which corresponds to an annual release of approximately 1.8 tonnes of Mn into the
Sydney atmosphere. As indicated in Section 8.1.4, this released Mn is expected to be in
the form of inorganic Mn compounds contained as components of fine particles, which
are not expected to immediately precipitate, and may remain suspended in the
atmosphere for prolonged periods.
It is readily shown that the effective height of the air column over a particular area is
6.15 km (see for example Connell and Hawker, 1986), and so this 1.8 tonnes of Mn
would be released into an atmospheric volume of 1550 km2 x 6.15 cubic kilometres, or
approximately 1013 m3. However, the assumption that the Mn particles would be
homogeneously distributed throughout a 6.15 km air column is unrealistic. A more
realistic assumption is to assume that the particles are only distributed in the lowest 615
metres (ie. 1012 m3).
In order to go any further it is now necessary to make some simplifying assumptions,
and while these are not entirely realistic they nevertheless allow for a first
approximation to the atmospheric Mn level. If it is assumed that the air column is
perfectly static, that the particulate matter is homogeneously distributed through the air
column volume and that none is precipitated with rain or through other mechanisms,
then after one year the atmospheric Mn level is estimated as 1.8 x 1015 nanograms/1012
m3 = 1800 ng/m3.
The assumptions made above are considered unrealistic in that no dispersion through
wind or by rain is considered. If it is assumed the particles remained suspended for an
average of 3 days without removal, as may potentially occur, albeit rarely following 3
consecutive windless days, then the atmospheric RME concentration could be as high
as 15 ng/m3 (see Table 7).
AVE Concentration for Mn
An AVE Mn concentration in air at ground-level may be estimated taking into account
losses due to wind dispersion out of the urban area. The average concentration at any
one time within the atmospheric box may be estimated as the influx rate minus the
emission rate from the atmosphere box.
An influx of 1.8 x 1015 nanograms Mn/year (4.9 x 1012 ng Mn/day) has been estimated
above. Emitted into an air volume of 1012 m3 each day, an average daily air
concentration of 4.9 ng/m3 has been estimated using this model (see Table 7).
Priority Existing Chemical Assessment Report Number 24
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2004 Scenario
This scenario assumes bulk sales of LRP have declined to 1000 ML as outlined in the
Use Section. With a treat rate of 72.6 mg/L this results in 72.6 tonnes of MMT (18.3
tonnes Mn). Assuming 20% (14.5 tonnes MMT/3.7 tonnes Mn) are released to the
Sydney atmosphere, the calculations and assumptions for this scenario are identical to
the above. Therefore, with a 20% release rate, 0.74 tonnes of Mn can be expected to be
released into the air column. The results of these estimations are summarised in Table
7.
Due to the complexities implied by uncertainties as to the use rate of MMT and the
prevailing atmospheric conditions in particular areas, these estimates of the atmospheric
Mn associated with particulate matter originating from exhaust emissions should be
treated as indicative only. The level of particulate matter in the atmosphere would be
very dependent on factors such as rain and wind, and it is likely that ambient and prior
weather conditions would impact on any particular daily measurement.
Table 7. Estimated average and reasonable maximum atmospheric Mn levels in
Sydney ?various MMT use scenarios and conditions
Atmospheric Dispersion (a)
Nil (b) AVE (c) RME (d)
Present Use
1800 ng/m3 4.9 ng/m3 15 ng/m3
36 tonnes of MMT
used as AVSR in
Sydney fuel.
2004
725 ng/m3 2.0 ng/m3 6.0 ng/m3
14.5 tonnes of MMT
used as AVSR in
Sydney fuel
Air column volume of 1012 m3 (ie. 615 m high x 1550x106 m2).
a.
b. No dispersion assumed throughout year (unrealistic).
c. AVE (Long-term Average), assumes wind dispersion with daily clearance of atmospheric box.
d. RME (Reasonable Maximum Exposure), assumes quiescent conditions for 3 days.
8.3.4 Release of Mn to the water compartment
If, as in the Present Use scenario above, the use of MMT were restricted to its addition
to LRP at a concentration of 72.6 mg/L (corresponding to 18 mg/L of Mn), then
annually approximately 1.8 tonnes of Mn would be released into the Sydney
atmosphere.
The majority of the released Mn will be in the +2 valence state in the form of either Mn
sulphate or Mn phosphate. Eventually, the particulate material will precipitate to the
surface where the soluble nature of both MnSO4 and Mn3(PO4)2 means that the Mn
would be leached from the particles and enter the water compartment. If it is assumed
that Sydney with a land area of approximately 1550 km2 receives an average annual
rain fall of 1 metre, then it is possible to estimate the worst case concentration of Mn in
Methylcyclopentadienyl manganese tricarbonyl (MMT) 31
storm water, assuming static atmospheric conditions as 1.8 x 106 (grams)/ 1550 x 106 x
1 (cubic metres) = 0.0012 mg/L. This is a small concentration and comparable with the
concentration of Mn in seawater, which is stated as 0.001-0.01 mg/L (CRC, 1977). This
estimate does not take into account wind dispersion of Mn from the atmosphere above
the urban area, which would reduce the estimated concentration.
8.4 Occupational exposure to MMT
Occupational exposure to MMT is possible during import, transport and handling of
imported MMT solutions and also during transport and handling of petrol and petrol
additives containing MMT.
MMT is imported in bulk as a 62% solution in a mixed hydrocarbon solvent (HiTEC
3062) in isotanks of 10,000L capacity and transported by road or rail to several fuel
refineries for addition to fuel. MMT is also imported in 205L steel drums and less
commonly in 450 L CYL-type steel cylinders as 60% or 62% solutions and transported
by road or rail to a small number of third party formulators for blending and packaging
into aftermarket fuel additives. Most of the blending and packaging is conducted by
two formulators. MMT is also imported in preformulated, prepackaged fuel additives
and with locally formulated fuel additives and bulk LRP are distributed to numerous
petrol stations and retail outlets.
8.4.1 Bulk fuel and fuel additive blending at refineries and formulators
Isotanks, steel drums and cylinders transported to fuel refineries or third party
formulators by road or rail will remain unopened prior to blending operations.
Consequently, in the absence of accidental puncture of import containers, exposure of
import and transport workers to MMT is not expected.
At refineries, isotainers are positioned by crane in a bunded area. A flexible hose is then
connected manually to the lower delivery flange of the isotank through which the MMT
solution is metered directly to the blending manifold at the designated LRP finished
product tank or firstly pumped to a storage tank prior to metering to the LRP finished
product tank. To facilitate emptying, the isotank is pressurised with nitrogen. All
pumping and metering of the MMT solution in the fuel blending operation are
conducted under automatic control in enclosed transfer systems. Bulk LRP containing
MMT is then pumped from the finished product tank via enclosed lines to terminals or
directly to road tankers.
At the refinery or terminals, blended LRP containing MMT at < 0.01% is pumped to
road tankers for transport to petrol retailers. Transfer involves a manual connection and
disconnection of a flexible transfer line between the LRP finished product tank or
terminal manifold and lower fill port of the road tanker.
A total of 10-20 personnel are involved in the import, storage and blending of the MMT
solution. At each site, fewer than 5 personnel are involved directly in the unloading of
the MMT solution from isotanks and these are engaged in these operations typically for
10 -15 minutes, 4 times per year.
At third party formulators, drums or cylinders of MMT concentrate are typically
opened in bunded areas and emptied by manually connecting a flexible hose to the dip
leg located at the top of the cylinder or manually inserting a spear through a bung at the
Priority Existing Chemical Assessment Report Number 24
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top of the 205 L drum. Cylinders may be pressurised with nitrogen to facilitate
emptying. MMT is then pumped to a closed mixing vessel or to storage. After emptying
drums and cylinders, residual MMT is captured typically by adding petroleum diluent
by pump, manually swirling the containers and pumping the residue to the mixing
vessel. After mixing, the formulated fuel additive containing MMT at < 10% w/w is
gravity fed to and packed in sealed plastic bottles of up to 500 mL capacity.
Typically at each formulator, up to 3 warehouse personnel and up to 3 blending and 3
filling personnel handle imported MMT solutions in imported drums, cylinders or filled
end-use plastic bottles. Blending activities typically occur for 2 - 8 hours/day for 2 ?2
days/year. Filling/packing activities may occur for up 15 hours/day for 2 days/year.
Quality analysis personnel test blended LRP and aftermarket additives and handle
samples during laboratory analysis. Sampling is conducted manually on a per batch
basis from several stopcocks located at various depths on the outside of the LRP
finished product tank and also from the additive blending tank. Quality analysis
personnel conduct sampling and laboratory analysis once per week for LRP blending
and approximately 4 days per year for additive blending.
The main routes of exposure of workers to MMT are dermal and ocular from slops and
spills during manipulation of transfer lines and spears and also sampling and laboratory
analysis. Despite the possibility of gas leakage if pressurised transfer is used, the low
vapour pressure of MMT (0.01 kPa at 20癈) renders inhalation exposure of workers
unlikely. Once in storage or blending tanks, exposure of refinery or formulation
workers during addition to bulk fuel or formulation of aftermarket additives would not
be envisaged given the enclosed, automatic nature of the blending/filling processes.
8.4.2 Petrol stations and maintenance workshops
At petrol stations, LRP will be transferred from road tankers to underground storage
tanks. In a similar fashion to unloading of imported MMT solution, transfer requires
that tanker drivers manually connect and disconnect flexible tansfer lines between the
tanker and storage tank. During this process, dermal and ocular exposure to diluted
MMT is possible from slops and spills. Notwithstanding the possible fitment of vapour
recovery systems, although contact with fuel vapours is also possible during transfer,
the low vapour pressure of MMT renders inhalation exposure of tanker drivers to MMT
unlikely. Potential exposure of drivers may occur frequently during the day in
metropolitan areas with numerous offloads and less frequently during tanker deliveries
to regional areas.
Similar exposure, mainly dermal, may be envisaged for petrol station workers during
dip measurement of underground tanks. Typically, dipping occurs for up to 10 minutes,
once per week. Automechanics at petrol stations and maintenance workshops may be
exposed also to diluted MMT in LRP and in aftermarket additives during maintenance
of automotive fuel systems. The extent of exposure during these activities is likely to be
highly variable.
8.5 Occupational exposure to manganese from MMT use
The combustion of MMT produces particulates containing Mn, with a majority of
particulates in the respirable size range. Several classes of workers are exposed
Methylcyclopentadienyl manganese tricarbonyl (MMT) 33
potentially to Mn in occupational settings not via exposure to MMT but to particulates
from automotive exhaust.
In addition to exposure to MMT, petrol station and maintenance workers may
experience occupational inhalation exposure to Mn particulates in exhaust emissions.
The exposure of petrol station attendants is likely to be highly variable depending on
the required duties ?purely retail versus petrol pumping, the level of customer traffic,
the separation of retail from service areas and the vehicle fleet i.e. cars using LRP
versus unleaded fuel.
Automechanics may be particularly exposed to Mn particulates when servicing
operating automotive engines in poorly ventilated workshops.
Attendants, security and other personnel who work in enclosed car parks such as
underground parking stations also have a potential for inhalation exposure to
particulates containing Mn during routine duties. Exposure to MMT for these workers
is unlikely given the enclosed nature of automotive petrol systems, low vapour pressure
of MMT and expected very low levels of MMT emissions in exhaust. Like service
station workers, exposure during the working day is likely to be highly variable and
dependent on the level of and proximity to customer traffic and the effectiveness of
ventilation of the enclosed parking station.
Professional drivers such as taxi and truck operators and road maintenance workers
may also be exposed to Mn from inhalation of particulates from automotive exhaust.
Again, exposure is likely to be highly variable and dependent on traffic, particulate
filtering within automotive airconditioning systems and, in the case of road workers,
whether work is on new, uncommissioned or light duty roads or on heavily trafficked
arterial roads repaired whilst in service.
8.5.1 Exposure data and estimates
Few data are available regarding personal exposure levels to MMT or to Mn as a result
of the use of MMT in fuels. The following limited data for personal 8-hour Time-
Weighted-Average occupational exposures (TWA8) to MMT (as Mn) have been
submitted for Ethyl facilities in USA, Canada and England for the period 1987 to 1991
(Albemarle Corporation 1994):
16-1600 (arithmetic mean 200) 礸/m3 (n = 12)
Manufacturing
< 40 - < 200 礸/m3 (n = 3)
Laboratory Analysis
< 100 礸/m3 (n = 2)
Shipping
Anecdotal exposure data for refinery handling have also been supplied by Ethyl
Corporation. These are based on data provided by Ethyl Corporation customers:
< 10 礸/m3 (TWA8)
Refinery Handling
References, location and details of the extent and type of sampling for these refinery
handling data are not available.
No information is available regarding Australian refinery exposures or occupational
exposure during formulation of aftermarket fuel additives. No MMT manufacture
occurs presently in Australia and so these manufacturing, laboratory analysis and
Priority Existing Chemical Assessment Report Number 24
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shipping data are not directly comparable to those of local occupational environments.
However, it is likely that local exposures to MMT would be much lower than those
associated with overseas manufacturing because Australian occupational use scenarios
involve handling MMT in diluted forms on a much more intermittent basis. Similarly,
exposures associated with local refinery handling are expected to be less than those
overseas due to the more limited use of MMT.
No quantitative data are available regarding personal exposures to or environmental
levels of MMT in workplaces in Australia. However, some limited overseas non-
manufacturing data are available. Zayed et al. (1999a) measured airborne MMT
(measured as Mn) and total and respirable (< 5 祄) Mn levels in selected occupational
microenvironments in Montreal. Stationary sampling was conducted over 36 hours and
six samples were collected at each site (outlined in Environmental Concentrations
Section 8.3.2). The highest levels of both MMT and total Mn were found at petrol
stations (MMT, total and respirable Mn were 12, 141 and 35 ng/m3 respectively) whilst
the highest levels of respirable Mn were found in the vicinity of an expressway (MMT,
total and respirable Mn were 6, 127 and 53 ng/m3 respectively). Lower levels of MMT,
total and respirable Mn were found in the underground car park (0.4, 78 and 30 ng/m3
respectively).
It should be emphasised that these are environmental monitoring data and their
relevance to personal occupational exposures is unclear.
In a limited personal occupational exposure study, Zayed et al. (1994) monitored the
exposure of garage mechanics and taxi drivers to airborne Mn (> 0.8 祄) using
personal breathing zone air samplers. Ten garage mechanics from the same garage and
ten taxi drivers were assessed for 5 consecutive working days and for 2 days off work.
For both worker groups, exposure levels were significantly higher at work compared to
off-work (Table 8).
Methylcyclopentadienyl manganese tricarbonyl (MMT) 35
Table 8. Personal total manganese exposure of Montreal taxi drivers and garage
mechanics (Zayed et al., 1994)
Off-Work At Work
Mean Mean
Number of Number of
Exposure Exposure
Samples Samples
(ng/m3) (ng/m3)
Taxi drivers (total) 7 19 24 48
Garage Mechanics
11 8 250 49
(total)
Open Workshops - 152 nr
Closed Workshops - 314 nr
nr ?not revealed
Garage mechanics showed very high levels of exposure compared to taxi drivers (mean
Mn exposures of 250 ng/m3 versus 24 ng/m3 respectively). Moreover, garage exposures
varied significantly depending upon whether garage doors were open or closed. Highest
levels were measured in closed garages (mean Mn exposure of 314 ng/m3), supporting
the notion that automobiles, whether as a result of the inhalation of exhaust or
generation of airborne particulates from servicing Mn-contaminated components, are
the source of Mn.
A further similar study of personal occupational exposures to Mn from automotive use
of MMT was conducted by Sierra et al. (1995) where personal exposures of 35 garage
mechanics to airborne Mn (> 0.8 祄) were compared to those of 30 nonautomotive
workers. In this study, garage doors were reported "mostly" closed and exhaust gases
were not always vented to the outside. The average Mn exposure for garage mechanics
at work was even higher than the previous study with Mn exposures at 448 ng/m3
versus 250 ng/m3 respectively (Table 9).
Table 9. Personal total manganese exposure of Montreal garage mechanics and
non-automotive workers (Sierra et al., 1995)
Off-Work At Work
Mean
Mean
Number of Number of
Exposure
Exposure
Samples Samples
(ng/m3) (ng/m3)
Non-automotive
8 60 44 143
workers
Garage Mechanics 12 59 448 160
Occupational exposure of mechanics was 10 times higher than that of non-automotive
workers at 44 ng/m3. Levels of other metallic particulates were also elevated within the
garage environment and the exact contribution to Mn exposures from the use of MMT
could not be determined. However, approximately 60 % of Mn particulates were < 1.5
Priority Existing Chemical Assessment Report Number 24
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祄 and approximately 37 % were < 0.93祄. Given that the majority of particulates
from MMT combustion are < 1 祄 (Ardeleanu et al., 1999; Roos et al., 2000), this
suggests that only up to one third of Mn particulates in the workshop resulted from
MMT combustion.
Occupational exposures to total (> 0.8祄) and respirable (< 5 祄) Mn particulates in
Canada were also studied by Zayed et al. (1996) for 9 taxi drivers and 20 office workers
in Toronto. For office workers, the average total and respirable Mn levels measured
over 7 days, 24 hours per day were 12 ng/m3 and 10 ng/m3 respectively. Levels were
significantly higher for taxi drivers at 28 ng/m3 and 15 ng/m3 respectively. The average
fraction of respirable to total Mn was 76-90%.
Personal exposures to airborne Mn were studied in London taxi drivers and office
workers in 1995 and 1996 by Pfeifer, Harrison and Lynam (1999) prior to and
following the introduction of MMT as a diesel fuel additive. Personal exposures to Mn
in total suspended particulates did not increase as a result of MMT introduction. For
PM2.5 Mn particulates, there were no significant differences between exposures of taxi
drivers and non-underground railway commuting office workers. Interestingly,
underground railway commuting office workers showed significantly higher Mn
exposures.
The extrapolation of these data to Australian occupational settings should be conducted
with extreme caution. As indicated in Section 8.3, background atmospheric levels of
Mn are an order of magnitude lower in Australia compared to Canada and this is
attributable at least in part to the more widespread, multifunctional use of MMT in
Canada. Also, no data are available to compare overseas and local work practices and
these may be subject significantly to local conditions. For example, autorepair, which is
identified in the above studies as a critical occupation with respect to exposure to
atmospheric Mn, is likely to occur more frequently within closed workshops with
greater contact with cars using MMT-supplemented fuels in Canada compared to
Australia. Finally, these Canadian studies are only of small duration (1-2 weeks) with
small sample sizes and the representativeness of the sampled populations cannot be
assessed.
Notwithstanding study uncertainties, these overseas microenvironmental and personal
exposure data suggest that automotive maintenance workshops are potential sites of
high airborne particulate Mn levels and that garage mechanics may experience
relatively high exposures to Mn from MMT use. However, given the potential
differences in occupational conditions and extent of use of MMT, it is likely that local
occupational exposures to Mn would be significantly less than those of Canada.
8.6 Public exposure
8.6.1 Consumer exposure
Exposure to MMT is likely to occur as a result of contact during refuelling vehicles or
adding aftermarket product to petrol tanks, contact during the use of LRP as a solvent
or cleaner or as a result of substance abuse (petrol sniffing). In the cases of deliberate
exposure to LRP petrol, the low concentrations of MMT in petrol and low vapour
pressure will probably limit the extent of exposure to MMT and exposure to the
petroleum solvent is likely to be of greater potential concern. Since they contain higher
Methylcyclopentadienyl manganese tricarbonyl (MMT) 37
concentrations of MMT, exposure to aftermarket products is likely to be of greater
potential concern.
Accidental dermal and possibly ocular exposure to MMT (and Mn) in petrol is possible
when refuelling vehicles and when adding aftermarket products to fuel tanks. The
concentration of MMT in LRP is about 72.6 mg/L (18 mg/L Mn). Assuming, as a worst
case, a person spills 200 mL of LRP onto the skin then they would be exposed to a
dermal dose of approximately 208 礸/kg bw of MMT (51 礸/kg bw Mn). Assuming
that 100 mL of an aftermarket product containing, for example, 7% v/v (approximately
10% w/w) MMT was spilt onto the skin, then a person would be exposed to a dermal
dose of approximately 130 mg/kg bw MMT (32.5 mg/kg bw Mn). The amounts to
which people will be dermally exposed will be highly variable and lower than the
above worstcase estimates.
Accidental ocular exposure as a result of splashes of LRP and/or aftermarket products
is also likely to occur only infrequently and involve very small amounts of MMT (Mn).
Ingestion exposure is generally unlikely, but, if aftermarket products are stored in or
around the home, accidental ingestion might occur in young children. Children between
one and a quarter and three and a half years of age can swallow approximately 4.5 mL
of liquid (Gosselin et al., 1976). A child (10kg) ingesting one mL of a product
containing 7% v/v (10% w/w) would receive an oral dose of 11.8 mg/kg bw MMT (2.9
mg/kg bw Mn). However, aftermarket products are likely to be stored in garages and
the information supplied indicates that such products are packaged in containers fitted
with child resistant closures.
Accidental ingestion of MMT in LRP could occur when syphoning petrol. Accidental
ingestion by a child could occur also if MMT containing LRP is stored in inappropriate
containers in or around the home environment. Australian National Hospital Morbidity
Data show approximately 133 hospital discharges/year between 1998 and 2000 were
associated with the toxic effects of petroleum products (AIHW, 2002). Victorian data
show that there were 75 hospital admissions between 1987 to 1994 involving children
below five years of age that were poisoned by petroleum fuels and cleaners including
kerosene. Data from a selection of Victorian hospitals showed that there were 16
emergency department presentations between 1989 and 1995 involving children below
5 years of age ingesting petrol. Three of the 16 had siphoned petrol from a car or lawn
mower and two had drunk petrol from drink bottles (Ashby and Routely, 1996).
Although no data was available on the amounts of petrol ingested, it is likely that only
small amounts of LRP would be accidentally ingested. Data collected by Watson et. al
(1983) show that the average volume of a swallow (of tap water) for a child up to 5
years of age is between approximately 1 and 7 mL and for a person between 5 and 18
years of age is between 2 and about 30mL. Given these low amounts of LRP and the
low concentrations of MMT in LRP, ingestion would involve potentially only very
small amounts of MMT and with the solvent nature of petroleum products, repeated
ingestion or ingestion of larger amounts e.g. 100mL or more is unlikely.
8.6.2 Indirect exposure via environment
Exposure to MMT
As outlined in Section 8.3.1, the atmospheric concentration of MMT is likely to be very
low due to the diffuse nature of releases and the rapid photochemical decomposition of
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the compound. Since there appears to be no Australian data on atmospheric
concentrations of MMT, no estimate of inhalation exposure can be made that is directly
relevant to Australian conditions. However, the mean atmospheric concentration of
MMT of 5 ng/m3 measured in Montreal (Zayed, 1999a) can be used as an example to
demonstrate that the lifetime average daily inhalation dose of MMT is likely to be low
(1.4 ng/kg bw/day for a 70 kg adult).
Inhalation exposure to MMT might be higher in microenvironments where the air
concentration is likely to be higher. e.g. in a service station. Although MMT has a low
vapour pressure (0.01 kPa at 20oC), some inhalation exposure to MMT is possible when
refuelling vehicles. No Australian data are available for the air concentration of MMT
in service stations. Zayed et al. (1999) measured the air concentration of MMT in
Canadian service stations as 12 ng/m3. Assuming that the time spent refuelling is 6
minutes/day (USEPA, 1997), an adult inhalation rate of 0.8 m3/hour, body weight of 70
kg, average lifespan of 75 years, all vapour inhaled is absorbed and refuelling occurs
once/week, then the lifetime average daily inhalation exposure to MMT during
refuelling is very low, as estimated below:
Lifetime average daily dose of MMT
= (12 ng/m3 x 0.8 m3/hr x 0.1hr/day x 3900 days)/(27375 days x 70kg)
= 0.002 ng/kg bw/day.
Section 8.3.1 states that very little release of MMT is expected in the soil compartment
of the environment, unless there is a gross spill of HiTEC 3062. Therefore it is likely
that public exposure to MMT as a result of soil contamination is likely to be very low.
Similarly, public exposure to MMT as a result of water contamination is also likely to
be very low, since, as outlined in Section 8.2.2, any MMT that does enter the water
compartment of the environment would be subject to photolysis and evaporation.
No information is available on the possible contamination of food with MMT, however,
public exposure via MMT contaminated food is likely to be very low, since the
expected low environmental concentrations of MMT should not result in significant
contamination of foodstuff with MMT.
Exposure to manganese via air
Although most MMT will be destroyed during combustion in the engine, a proportion
of exhaust emissions will contain MMT combustion products in the form of inorganic
Mn compounds. These combustion products have the potential to increase public
exposure to airborne Mn. Using atmospheric PM2.5 Mn concentrations from the most
realistic atmospheric dispersion model (Section 8.3.3), an estimate can be made for the
potential public inhalation exposure to Mn according to the two use scenarios, firstly
where LRP market share is maintained at present levels and use patterns (Present Use
scenario) and then when it is reduced to aftermarket use only (2004 scenario).
The mean air concentration estimated for Sydney will be used as a basis for estimating
lifetime exposure of the Australian public. Since most of the Mn-containing
combustion products of MMT are associated with particles of 2.5 祄 or smaller and the
PM2.5 fraction of air particulate matter is of most toxicological significance, the PM2.5
Mn concentration for Sydney of 3 ng/m3 (Table 6) is used as a "baseline" level of
exposure. The estimated atmospheric Mn levels given under the Present Use scenario
Methylcyclopentadienyl manganese tricarbonyl (MMT) 39
and 2004 scenario (Section 8.3.3) represent the estimated increase in air Mn
concentrations and exposures attributable to MMT combustion when MMT is used as
an AVSR. As a worst-case, it could be assumed that indoor and outdoor air
concentrations of respirable Mn are the same and therefore people will be exposed to
ambient air Mn for 24 hours/day. The following exposure estimates also assume an
average respiration rate of 20 m3/day for a 70 kg adult and assume a 60% pulmonary
deposition for inhaled particles in the size range expected from MMT combustion
(McClellan and Henderson, 1989; USEPA 1994d). The calculation of dose assumes
100% absorption.
Table 10. Lifetime average estimated human exposure to Mn in ambient air
Average Ambient
Human Exposure Human Dose
Scenario Air Concentration
(ng/day) (ng/kg bw/day)
(PM2.5 Mn ng/m3)
Baseline (PM2.5 Sydney) 3 36 0.51
Increase due to MMT ?Present
Use: Maintained LRP Market 4.9 58.8 0.84
Share
Increase due to MMT - 2004:
2 24 0.34
Decreased LRP Market Share
These estimated potential exposures to respirable Mn are lower than those reported for
other countries where MMT is used widely. Based on the mean ambient air
concentration of respirable Mn particulates (36 ng/m3) reported by Zayed et al. (1999a),
average intakes of respirable Mn for Montreal can be calculated at 720 ng/day. A
similar calculation can be made based on mean outdoors PM2.5 Mn levels of up to 17.1
ng/m3 measured in Toronto by Pellizzari et al (1999). In this case, average intakes of
respirable Mn total 352 ng/day. This study also reported Mn levels from personal air
monitoring. Across 925 subjects, a mean PM2.5 Mn level of 14 ng/m3 (median 8.5
ng/m3) was derived giving a daily exposure derived from personal exposure data of 280
ng/day.
Loranger and Zayed (1997) estimated the average air concentration of respirable Mn in
a low traffic urban site (botanical gardens, approx 15 ng/m3) in Montreal and from this
data a daily exposure of approximately 300 ng/day can be calculated. Ambient air PM2.5
concentrations of approximately 5-50 ng/m3 were reported by Wood and Egyed (1994)
in a range of Canadian cities with most having ambient air PM2.5 concentrations in the
range of 10-20 ng/m3. From these data, mean inhalation intakes can be estimated at
200-400 ng/day for Canadian urban centres without Mn emitting industries.
Data from ambient air PM2.5 Mn monitoring in Riverside California in 1990 (Pellizzari
et al., 1992 as cited in USEPA 1994) showed a 24 h median concentration of
approximately 10 ng/m3 from which exposures of about 200 ng/day can be calculated.
It should be noted that the ambient air values reported overseas include Mn due to
MMT combustion as well as other airborne sources such as windblown dusts. It is very
difficult to determine the proportion of ambient air Mn that is directly attributable to
MMT combustion. Based on the data of Lyons et al. (1993) the USEPA (1994c)
concluded that approximately 75% of the PM2.5 Mn collected in the Los Angeles basin
Priority Existing Chemical Assessment Report Number 24
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was from automotive sources. Using dispersion modelling estimates, Loranger and
Zayed (1997) predicted the contribution of automotive sources to background Mn
concentrations as 50% at 25m from a Canadian highway and only 8% at 250m from the
road. However, based on a comparison of respirable Mn concentrations and MMT use
in Canadian urban centres, Wood and Egyed (1994) concluded that MMT use did not
contribute significantly to ambient air respirable Mn concentrations.
Crump (2000) in analysing Mn exposures in Toronto also concluded that most of
personal Mn exposure in this city was from non-MMT sources. Evidence cited for this
was a negative correlation between MMT usage and PM2.5 Mn levels and a reduction of
average exposures by 40% by eliminating study participants with Mn exposures from
known non-MMT sources together with the existence of multiple non-MMT sources for
the remaining Mn exposure of study participants.
Ambient air concentrations of Mn, and hence exposures, are also expected to vary
significantly dependant upon the environment in which people live. People living in
rural areas would be expected to have lower exposure than people living in cities and
those living in areas affected by large Mn emitting industries could be expected to have
the highest levels of exposure. For example, people living in Canberra would be
expected to have exposures much lower than those living in any other major Australian
city (Table 6). Although the contribution of regional Mn emitting industries to Mn
levels in Launceston is unknown, based on the data of Ayers et al (1999), those living
in this city would have had Mn exposures of up to approximately 500 ng/day (PM2.5)
during 1997. People living in rural/remote areas would be expected to have very low
exposures to respirable Mn. In the USA, PM2.5 Mn concentrations in national parks
were measured at 1 ng/m3 from which exposures of approximately 20 ng/day can be
calculated (Wallace and Slonecker, 1997). Given that the estimated respirable Mn
concentration measured in Canberra in 1997 was below 1 ng/m3, exposures of
Australians living in rural and remote regions is expected to be even lower. Overseas
data also reflect the relatively high exposures expected in areas with Mn emitting
industries. Based on ambient air data reported by Wood and Egyed (1994), exposures
of up to 3160 ng/day can be calculated for people living in Canadian cities with large
Mn emitting industries. Similarly, WHO (1981) estimated exposures of up to 10 000
ng/day in areas associated with ferro- or silicomanganese industries with 24-hour peak
values over 200 000 ng/day.
It should also be noted that ambient air concentrations might not always reflect the
actual exposure of individuals living in a given area, because typical human activity
patterns result in time spent in microenvironments with higher or lower concentrations
of a pollutant and for which there is generally no monitoring data. Hence, a measure of
personal exposure to a compound is preferable to ambient air data, and that estimate
should be representative of the population of interest throughout the time period of
interest.
Canadian personal and ambient air monitoring studies demonstrate outdoor
microenvironments of importance e.g. in a vehicle, at a petrol station, an underground
car park, the subway and areas of high traffic density (Loranger et al., 1997; Zayed et
al. 1999; Pellizzari et al., 1999; Crump 2000). Also, the amount of time spent indoors
or outdoors can also be a significant determinant of personal exposure to respirable Mn.
From the Toronto study of Pellizzari et al. (1999), Crump (2000) observed that the
mean indoor residential air concentration of respirable Mn of 5.5 ng/m3 (PM2.5) was
approximately 60% of that of the average air concentration measured at several outdoor
Methylcyclopentadienyl manganese tricarbonyl (MMT) 41
residential sites. Also, the earlier data of Pellizzari et al. (1992) as reported by the
USEPA (1994c) showed that the median ambient indoor air concentration of PM2.5 was
about 80% of the outdoors concentration measured outside the homes of participants.
No Australian ambient air Mn concentration data are available for particular outdoor
microenvironments or indoor air and no personal monitoring studies have been
completed in Australia. Therefore, the above worst-case estimate of exposure cannot be
refined without assuming that overseas data are applicable to Australian conditions.
An environmental and epidemiological study of Mn from MMT use is currently being
conducted in Australia. The objectives of the project are to determine the contribution
of MMT use to Mn levels in air, dust, soil and water and also blood and urine Mn levels
in children aged 1-5 years. At the time of writing, 78 exposed children ranging in age
from 6 to 18 months have been recruited to the study. All environmental and biological
sampling has been completed for this whole cohort with repeated samplings conducted
in approximately half. Analytical results for all samples have been obtained. No results
are yet available. The project has been delayed by difficulties with funding and further
delays are likely to result in termination of the project.
Exposure to manganese via food
Food is the most significant source of exposure to Mn. Fardy et al. (1992) as reported
by Wood and Egyed (1994) estimated the average Australian dietary intake of Mn to be
5 530 礸/day for males and 2 960 礸/day for females (an average of 4 245 礸/day for
both sexes). According to New Zealand Ministry of Health (1999), median adult Mn
intake is 4 327 礸/day in New Zealand. Assuming 3% of this dietary intake is absorbed
from the gastrointestinal tract (WHO, 1981), the systemic dose of Mn from the diet can
be estimated as approximately 127 礸/day or 1.82 礸/kg bw/day (for a 70 kg adult).
The WHO (1981) estimated the average daily Mn intake from the diet to be in the range
of 2 000 ?9 000 礸/day and estimates of dietary intake of Mn from the USEPA (1984)
give a typical intake at 3 800 礸/day.
It is conceivable that Mn levels in foodstuff may be increased as a result of
environmental contamination with the combustion products of MMT. There are no
Australian studies on the possible contribution of MMT combustion product to food
Mn. Given the expected low soil, water and atmospheric levels of MMT combustion
products (especially in rural areas), it is considered that the contribution of MMT
combustion products to Mn intake from foodstuff is likely to be very low.
Exposure to manganese via water
In Australian reticulated water supplies, the Mn concentration can be up to 0.25 mg/L
with typical concentrations usually less than 10 礸/L (NHMRC, 1996). Assuming that a
person drinks up to 2L/day, intake from drinking water can be up to 500 礸/day, but is
probably usually about 20 礸/day or less. Assuming 3% of this intake is absorbed from
the gastrointestinal tract, the systemic dose of Mn from the diet can be estimated as
approximately 8.6 ng/kg bw/day for a 70 kg adult. The USEPA (1984) estimates the
typical concentration of Mn in the water to be 4 礸/L and intake to be 8 礸/day.
Manganese concentrations in Canadian drinking water were generally below 50 礸/L,
but a conservative value of 100 礸/L was used for a Canadian exposure assessment
(Wood and Egyed, 1994) giving intakes at approximately 200 礸/day.
Priority Existing Chemical Assessment Report Number 24
42
The concentration of Mn in Sydney's stormwater as a result of MMT combustion is
estimated at 1.2 礸/L (Section 8.3.4). Given the expected low water concentrations of
MMT combustion products (especially in water catchment areas), it is considered that
the contribution of MMT combustion products to Mn intake from water is also likely to
be very low.
Other possible sources of exposure
Other possible sources of Mn exposure include smoking and soil ingestion. Manganese
exposures as a result of smoking are likely to contribute significantly to the total
inhalation exposure to Mn in some individuals. The personal exposure data analysed by
Crump (2000) show that the median PM2.5 Mn exposure was higher for smokers (9.2
ng/m3) than non-smokers (8.3 ng/m3). People exposed passively to environmental
tobacco smoke (9.0 ng/m3) had exposure levels similar to smokers, whereas those not
exposed to tobacco smoke from any sources had the lowest levels of personal exposure
(7.7 ng/m3). Manganese exposures as a result of smoking are outside the scope of this
report and will not be considered further.
It is conceivable that Mn produced as a result of MMT combustion could increase soil
levels of Mn and hence increase Mn exposures as a result of soil ingestion. However,
given that soil Mn concentrations in Australia are not expected to be significantly
increased by MMT use, then Mn exposure as a result of soil ingestion is not expected to
increase.
Table 11. Summary of main sources of human exposure to Mn*
Source of Exposure Estimated Absorbed Estimated Absorbed Dose - With
Dose ?No Exposure Exposure to MMT (ng/kg bw/day)
to MMT (ng/kg
bw/day)
Air 0.5 0.85-1.35
Food 1820 1820**
Water 8.6 8.6**
Total 1829.46 1828.9-1829.4
* - for a 70 kg adult
**- no increase expected due to MMT use
Methylcyclopentadienyl manganese tricarbonyl (MMT) 43
9. Kinetics and Metabolism of MMT
9.1 Absorption
Although no studies were located describing the absorption of MMT, acute and
repeated dose studies indicate that absorption does occur via dermal, oral and
respiratory routes, as demonstrated by the toxic effects observed following MMT
administration.
9.2 Distribution
The distribution of MMT was examined 1.5-96 hours after subcutaneously
administering a single dose of MMT (4 mg/kg bw) to male Sprague-Dawley rats. The
level of Mn in the blood, lungs, liver and kidney was increased throughout the study
and peaked at 3-6 hours post injection. Levels of brain Mn were not significantly
increased in treated animals. The level of Mn in the lung, liver, kidney, and blood at 3
hours post injection was 9 mg/kg, 2.75 mg/kg, 3.9 mg/kg, and 0.75 mg/kg respectively.
The number of animals per treatment group was not stated (McGinley et al., 1987).
A single subcutaneous injection of MMT (4 and 10 mg/kg bw) to male Sprague-
Dawley rats resulted in a significant increase in lung Mn content. After 24 hours rats
that had not received MMT had 0.7 礸 Mn per lung. By comparison rats that received 1
mg/kg bw MMT had 6.5 礸 Mn per lung, and those that received 2.5 mg/kg bw MMT
had 20.1 礸 Mn per lung. An additional study was performed assessing Mn lung burden
resulting from MMT administration in the presence of piperonyl butoxide, a
cytochrome P450 monooxygenase inhibitor. A 1 hour pre-treatment with piperonyl
butoxide (400 mg/kg bw) was found to protect against lung Mn accumulation resulting
from a single subcutaneous injection of 4 mg/kg bw MMT (approximately 5 礸
Mn/lung compared with 10 礸 Mn/lung). Heptane extraction of lung homogenates from
MMT-treated rats indicated less than 2% of the pulmonary Mn was extractable,
suggesting the presence of metabolites as opposed to MMT. Furthermore the decrease
in Mn lung content in the presence of piperonyl butoxide suggests the presence of
cytochrome P450 dependent monoxygenase metabolites. Each treatment group
contained between 4 and 9 rats (Clay and Morris 1989).
The level of Mn in the brain of CD-1 mice was significantly increased by subcutaneous
injection of MMT. In an acute study mice received a single MMT injection and were
sacrificed after 24 hours. Mice in the control group were found to have 0.61 礸 Mn/g
brain. By comparison mice that received 11 mg Mn/kg bw MMT injection had 0.93 礸
Mn/g brain, and those that received 22 mg Mn/kg bw MMT injection had 1.35 礸 Mn/g
brain. In a separate chronic study mice received 10 injections (given on alternate days)
and were sacrificed 24 hours after the tenth injection. At the end of the study mice in
the control group had 0.64 礸 Mn/g brain, while mice receiving 11 mg Mn/kg bw
MMT had 1.37 礸 Mn/g brain, and those receiving 22 mg Mn/kg bw MMT had 3.33 礸
Mn/g brain. On a temporal basis the concentration of brain Mn reached a level
approximately twice that of controls within 4-8 hours post treatment and remained
elevated for the length of the study. The number of animals per treatment group was not
stated (Gianutsos et al., 1985).
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The disposition of MMT was assessed in male ddY mice after chronic oral
administration of MMT in food (0.5 g Mn/kg food) for 12 months. Daily food intake
per mouse was reported as 3.6 g for controls and 3.1 g in the MMT-treated group. At
the end of the exposure period there was significantly more Mn in the liver, kidney,
pancreas, sublingual gland, lung and muscle in the MMT-treated group than in the
control group. The highest level of Mn in MMT-treated mice was observed in the
kidney (approximately 12.5 礸 Mn/g ww), followed by the thyroid gland (12 礸 Mn/g
ww), then the liver (10.5 礸 Mn/g ww), prostate (7.5 礸 Mn/g ww) and sublingual
gland (7 礸 Mn/g ww). The level of Mn in blood was significantly elevated in MMT-
treated mice when compared to controls. The blood Mn concentration was 1.12 ?0.19
礸/mL creatinine in the MMT group and 0.14 ?0.05 礸/mL creatinine for the control.
The weight gain of MMT-treated mice was significantly reduced after 9 months of the
treatment and remained depressed until the study was concluded. Each treatment group
contained between 4 and 6 animals (Komura and Sakamoto 1992).
An increase in the concentration of Mn in the brain of mice was reported following
either a 12 months treatment with MMT at 0.5 g Mn/kg in food or a single IP MMT
injection (100-2000 mg/kg bw in propylene glycol or corn oil) (Komura and Sakamoto
1994; Fishman et al., 1987) (See Section 11.11).
The disposition of MMT was investigated in male Charles River rats following oral and
intravenous (IV) administration of [54Mn]MMT. One day following oral administration
of 2.5 mg [54Mn]MMT in 0.2 mL Wesson oil, the highest 54Mn concentrations were
observed in the liver, lungs, kidneys, urinary bladder, pancreas, and abdominal fat.
Nine days following oral administration, the highest 54Mn concentrations were
observed in the kidneys, liver, pancreas, and lungs. Each treatment group contained 12
animals. The concentration of 54Mn in individual tissues was not reported (Moore et al.,
1974).
The concentration of tissue Mn was investigated in COBS rats following a single oral
dose of MMT at 15-150 mg/kg bw in Wesson oil. A number of animals that received
45-150 mg/kg bw of MMT died within 6 days post treatment. The concentration of Mn
in selected tissues (duodenum, kidney, liver, lung, heart and brain) of rats that died was
significantly increased and generally in a dose dependant manner. At 14 days post
treatment, with the exception of the lung, the levels of tissue Mn had fallen to
approximately normal levels. Each treatment group contained 10 animals. No statistical
analysis was performed (Hysell et al., 1974).
Repeated dermal contact of MMT (0.4-16 g/L) in gasoline solutions (with or without
tetraethyl lead) in rabbits (5 days/week, for 14 weeks), did not result in increased organ
Mn concentrations that could be directly attributed to MMT exposure. In contrast, there
was an increase in lung Mn levels in rats dermally exposed to MMT for 5 days/week,
for 6 months rats. The level of Mn in the brain, kidney and liver was normal. Each
treatment group contained 3 rabbits and an unknown number of rats. The distribution of
Mn was also examined following inhalation exposure in several species. When guinea
pigs, rats, and cats were exposed to airborne MMT for 7 hours per day on each of 45 or
150 days, an increase in liver, kidney, and lung Mn levels were observed. The highest
values were observed in the cat, then the rabbit, rat and guinea pig. The highest Mn
levels were observed in the liver, followed by the kidney, lung, heart and urine. Results
of 1 rabbit, post exposure, indicated rapidly decreasing levels of Mn in tissues, which
were within normal range by day 21. Two dogs, 1-2 rabbits, and an unknown number
Methylcyclopentadienyl manganese tricarbonyl (MMT) 45
of cats, rats and guinea pigs were used in each treatment group (Witherup et al
Unknown date d).
The distribution of Mn in male golden hamsters and male outbred albino rats was
investigated following exposure to MMT combustion products generated using a 1972
Chevrolet 350 CID (cubic inch displacement) engine dynamometer system. Emissions
were derived by passing exhaust generated from the combustion of fuel consisting of
indolene "clear" containing MMT at 0.25 g Mn/gallon through a muffler, followed by
dilution (25:1) with clean conditioned air. The final diluted emissions were split in two
with one half being irradiated prior to exposure to animals. Irradiated emissions
typically contained 855 礸/m3 particles (0.29 祄) consisting of 117 mg/m3 Mn
(13.7%). Nonirradiated emissions typically contained 635 礸/m3 particles (0.26 祄)
consisting of 131 mg/m3 Mn (20.7%). Animals were fed a low Mn diet and exposed for
8 hours per day for 56 consecutive days. At the end of the exposure period, the
concentration of Mn in the brain, liver and lung was significantly increased in the
irradiated emission group when compared to controls. In the nonirradiated emission
group, heart Mn levels were reduced while brain and liver Mn concentration were
significantly increased. Kidney Mn levels were unaffected. Similar results were
obtained with animals fed a regular (higher) Mn diet. No difference in Mn
concentration was observed in the hamster in all tissues examined. The number of
animals per treatment group was not stated (Moore et al., 1975b).
The distribution of Mn in various tissues has also been investigated in rats and monkeys
following inhalation of the combustion products of MMT according to a procedure
described by Rinehart, (1975) and Ulrich et al. (1979a). Briefly, the experimental
procedure involves generating MMT combustion products by burning MMT vapours in
a propane flame, which reportedly produces a solid product consisting of Mn oxide
(Mn3O4) with an aerodynamic diameter of approximately 0.11?(Ulrich et al., 1979a).
The animals were exposed for 24 hours per day for nine months to 11.6-1152 礸
Mn/m3 as Mn oxide (Mn3O4) aerosol. After nine months the level of Mn in the kidney,
lung, and blood were significantly increased when compared to controls. A significant
increase in spleen Mn levels was also observed in the monkey. The level of Mn in the
liver was unaffected in both species. Six months post exposure the level of Mn in the
spleen of rats was slightly elevated at low dose and reduced in the blood at high dose in
rats. The Mn content in all other tissues examined in both species was normal. Each
treatment group contained 15 male and 15 female rats and 4 male and 4 female
monkeys (Rinehart, 1975; Ulrich et al., 1979b,c).
9.3 Metabolism
The biotransformation of [54Mn]MMT was assessed in vitro using brain, liver, lung and
kidney homogenates from male Charles River rats. Liver homogenates were found to
metabolise 64.2% of [54Mn]MMT to inorganic 54Mn within 20 minutes, at a rate of 8.02
ng/min/mg tissue. Lung homogenates metabolised 26.9% of the administered
[54Mn]MMT at 0.07 ng/min/mg tissue, kidney homogenates 2.59% at 0.11 ng/min/mg
tissue, and brain homogenates 1.64% at 0.07 ng/min/mg tissue (Moore et al., 1974).
Hanzlik et al. (1980a) investigated the metabolism of MMT in male Sprague-Dawley
rats. Intraperitoneal pre-treatment with phenobarbital (60 mg/kg bw), an inducer of the
cytochrome P450 system, significantly reduced the incidence of death in rats after oral
administration of MMT (125 mg/kg bw in corn oil). Each treatment group contained
Priority Existing Chemical Assessment Report Number 24
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between 5 and 7 animals (Hanzlik et al., 1980a). This result suggests that MMT is
metabolised by the cytochrome P450 system.
In a separate study investigating the metabolism of MMT in male Sprague-Dawley rats,
Hanzlik et al. (1980b) demonstrated that a single oral dose of [H3]MMT (125 mg/kg
bw) resulted in two major urinary metabolites, carboxycyclopentadienyl manganese
tricarbonyl (CMT) ((CO3)MnC5H4CO2H), and hydroxymethylcyclopentadienyl
manganese tricarbonyl (HMT) ((CO3)MnC5H4CH2OH). Each treatment group
contained between 3 and 6 animals. In vitro the metabolism of MMT by liver and lung
microsomes was demonstrated to be cytochrome P450 dependant, in that it requires
NADPH (an essential cofactor for cytochrome P450 activity) and is inhibited by carbon
monoxide and N-decylimidazole (inhibitors of cytochrome P450 activity). Rat liver
microsomes were found to metabolise MMT in vitro with a Km of 78 礛 and a Vmax of
3.12 nmol/mg protein/min. The Km for MMT metabolism was unchanged while the
Vmax doubled when liver microsomes from phenobarbital (60 mg/kg bw) treated rats
were used. In fact 90% of MMT was metabolised within 15 minutes by liver
microsomes from phenobarbital treated rats. Lung microsomes were also found to
metabolise MMT, but this effect was not enhanced by phenobarbital.
The metabolism of MMT in male rats was also investigated after a single subcutaneous
injection of MMT at 2 礸 Mn/g bw in propylene glycol. Urine collected from MMT-
treated rats 25 minutes after administration was found to contain a single Mn peak
when analysed by high-performance liquid chromatography with a laser-excited atomic
fluorescence detector. The single metabolite was identified as CMT. The urine from the
control group contained no detectable Mn species. The number of animals per treatment
group was not stated (Walton et al., 1991).
The metabolism of MMT in female LAC-P Wistar rats was investigated after a single
IP injection (4 and 6 mg/kg bw in oil). Inhibitors of the cytochrome P-450 2B
isoenzyme (O,O,S-trimethylphosphorodithioate, bromophos, 2,4-dichloro(6-
phenylphenoxy)ethylamine and p-xylene) reduced the pulmonary toxicity of MMT by
approximately 10-fold as determined by LD50 values and lung weight. Inhibitors of
cytochrome P-450 1A, 2E and 4B isoenzymes had no effect on the pulmonary toxicity
of MMT. Each treatment group contained 5 animals. These findings suggest that the
cytochrome P-450 2B isoenzyme is responsible for the metabolism of MMT in rats
(Verschoyle et al., 1993).
9.4 Elimination and excretion
The toxicokinetics of Mn resulting from a single oral dose of MMT was examined in
Sprague-Dawley rats. MMT was administered orally by gavage at 20 mg MMT/kg bw
and blood samples were taken 0-456 hours post treatment. Plasma Mn levels reached a
maximum concentration (Cmax) of 0.93 礸/mL between 2-12 hours following MMT
administration (Tmax = 7.75 hr). From these values the plasma half-life (T1/2) of Mn
following MMT administration was determined as 55.2 hours. The clearance of MMT-
derived plasma Mn was extremely slow at 0.09 L/h kg. The authors noted that the
plasma Mn T1/2 was longer in female (68.4 hrs) than male (42 hrs) rats. Furthermore the
clearance rate of plasma Mn was slower in female (0.07 L/h kg) than male (0.11 L/h
kg) rats. Each treatment group contained 4 male and female animals (Zheng et al 2000).
The toxicokinetics of MMT in Sprague-Dawley rats has also been examined by Hanzlik
et al. (1980a). A single IP injection of [H3]MMT (30 mg/kg bw in corn oil) to
Methylcyclopentadienyl manganese tricarbonyl (MMT) 47
phenobarbital (60 mg/kg bw) pre-treated rats resulted in a linear increase in Mn and H3
concentrations in bile. During the first 6 hours following [H3]MMT injection
approximately 13% of the administered H3 was excreted in the bile. The concentration
of Mn in the bile 6 hours post injection of MMT was 25-40 ppm. The Mn concentration
was 50-130 times higher in MMT-treated than in control rats. The toxicokinetics of
MMT was also assessed following a single IV injection of MMT (10 mg/kg bw) to
phenobarbital (60 mg/kg bw) pre-treated rats and control animals. This resulted in an
increase in the biliary excretion of MMT from 3 mg/kg bw/hr (MMT alone) to 5.7
mg/kg bw/hr (MMT + Phenobarbital). Each treatment group contained between 4 and 6
animals.
In a separate study investigating the toxicokinetics of MMT in male Sprague-Dawley
rats, Hanzlik et al. (1980b) demonstrated that 48 hours after a single oral dose of
[H3]MMT (125 mg/kg bw), urinary and faecal excretion of H3 accounted for 81% and
2-4% respectively of administered MMT. It was also shown that 67% of the H3 in the
urine was CMT and 14% was in the form of HMT. In a separate study it was shown
that a single IV injection of [H3]MMT (10 mg/kg bw) resulted in 12% of the H3 being
present in the bile within 30 minutes. This was increased to 24% in phenobarbital (60
mg/kg bw) pre-treated rats. CMT and HMT accounted for 49% and 18% respectively of
the total biliary H3. Each treatment group contained between 3 and 6 animals.
The toxicokinetics of MMT in male rats was also investigated after a single
subcutaneous injection of MMT at 2 礸 Mn/g bw in propylene glycol. Urine collected
from MMT-treated rats 25 minutes after administration was found to contain a single
metabolite, CMT, which accounted for 1-4% of the total Mn administered as MMT.
The urine from the control group contained no detectable Mn species. The number of
animals per treatment group was not stated (Walton et al., 1991).
The elimination and excretion of MMT was investigated in male Charles River rats
following oral and IV administration of [54Mn]MMT. Rapid clearance of 54Mn was
observed in the first several days following oral administration of 0.5 or 2.5 mg
[54Mn]MMT in 0.2 mL Wesson oil. Clearance was due to excretion in urine and faeces.
During the first 24 hours following oral administration of 2.5 mg [54Mn]MMT, rats
excreted 73% of the administered 54Mn. Urine was determined to contain 36% of the
excreted 54Mn. In a similar manner to that observed for oral dosing, IV administration
of [54Mn]MMT (0.34 mg Mn/rat) in ethanol resulted in rapid clearance of 54Mn within a
few days. Again clearance was due to excretion via urine and faeces, with more in the
faeces. Each treatment group contained 12 animals (Moore et al., 1974).
The excretion of MMT was assessed in male ddY mice after chronic oral administration
of MMT in food (0.5 g Mn/kg food) for 12 months. Daily food intake per mouse was
slightly lower in the MMT-treated group. The level of Mn in urine was significantly
elevated in MMT-treated mice when compared to controls. The mean urinary Mn
concentration was 112 mg/g creatinine in the MMT group and approximately 2 mg/g
creatinine for the control. The excretion of Mn in the urine of MMT-treated rats
constituted 5.4% of the daily oral intake. Each treatment group contained between 4
and 6 animals (Komura and Sakamoto 1992).
The level of Mn in the urine of dogs exposed to 12 mg/m3 MMT for 7 hrs/day, 5
days/week, for nine weeks, was elevated at all time points above controls. In rabbits
exposed to 17.9 mg/m3 MMT (12 x 7 hr exposures) the level of Mn in urine was found
to increase during days of exposure, then rapidly declined on days when no exposure
occurred. The level of urine Mn returned to normal within 5 days of the last exposure.
Priority Existing Chemical Assessment Report Number 24
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A similar pattern of urine Mn content was observed in a rabbit exposed to 150 seven-
hour exposures (Witherup et al Unknown date d).
9.5 Summary
Acute and repeated dose toxicity studies indicate that MMT is absorbed via dermal,
oral and respiratory routes. Disposition studies in animals indicate that the liver, kidney,
brain, and lung are the primary sites of Mn accumulation following oral or dermal
exposure to MMT. Manganese also accumulated in the pancreas, sublingual gland,
thyroid, prostate, muscle, duodenum, urinary bladder, heart, abdominal fat and blood,
but to a lesser extent. Inhalation exposure of rats and monkeys to MMT combustion
products resulted in the accumulation of Mn in the brain, liver and lung. The finding in
rats that less than 2% of pulmonary Mn resulting from subcutaneous exposure to MMT
was extractable with heptane, suggests the presence of metabolites as opposed to MMT.
Studies investigating the biotransformation of MMT in vitro indicate the liver is the
predominant site of MMT metabolism, followed by the lung, kidney and brain. As the
metabolism of MMT in lung and liver microsomes in vitro is inhibited by carbon
monoxide and N-decylimidazole, it is likely the cytochrome P-450 monoxygenase
enzyme is responsible for the metabolism of MMT in rats. MMT and its metabolites are
predominantly excreted in the urine and faeces of rats. The most abundant MMT
metabolite was determined to be CMT followed by HMT.
Methylcyclopentadienyl manganese tricarbonyl (MMT) 49
10. Toxicity of MMT
10.1 Acute toxicity
Acute lethality studies are summarised in Table 12.
The major acute toxic effects of MMT include damage to the lungs by all routes,
kidney, liver and spleen effects, tremors, convulsions, dyspnea and weakness.
Table 12. Summary of MMT acute lethality studies
Route Species Result Reference
LC50 (4hr) > 2 mg/m3
Inhalation Rat Moore et al., 1975a
LC50 (1hr) = 247 mg/m3
Rat Ethyl Corporation, 1976h; Hinderer,
1979
LC50 (4hr) = 76 mg/m3
Rat Ethyl Corporation, 1976h; Hinderer,
1979
LC50 (1hr) > 19.8 g/m3 Ethyl Corporation, 1976a
Rat
(approx.)*
LC50 (1hr) = 220 mg/m3
Rat Witherup et al, Unknown date b
Rat (f)a
Oral LD50 = 22.9 mg/kg bw Witherup and Larson, 1965
Rat (f)b LD50 = 16.8 mg/kg bw Witherup and Larson, 1965
Rat (m)a LD50 = 38.5 mg/kg bw Witherup and Larson, 1965
Rat (m)b LD50 = 23.7 mg/kg bw Witherup and Larson, 1965
Rat (m) LD50 = 175 mg/kg bw** Witherup and Roell, 1965
Rat (f) LD50 = 89 mg/kg bw** Witherup and Roell, 1965
Rat LD50 = 58 mg/kg bw Hysell et al., 1974; Moore et al., 1975a
Rat LD50 = 58 mg/kg bw Ethyl Corporation, 1975a; Hinderer,
1979
Rat LD50 = 175 mg/kg bw* Ethyl Corporation, 1976b
Rat LD50 = 50 mg/kg bw Hanzlik et al., 1980a
Rata LD50 = 23-176 mg/kg bw Witherup et al., Unknown date b
Ratb LD50 = 9->80 mg/kg bw Witherup et al., Unknown date b
Mouse LD50 = 230 mg/kg bw Ethyl Corporation, 1977c; Hinderer,
1979
Mouse (f) LD50 = 60 mg/kg bw Majima, 1985
Priority Existing Chemical Assessment Report Number 24
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Table 12. Summary of MMT acute lethality studies (cont.)
Route Species Result Reference
Mouse (m) LD50 = 34 mg/kg bw Majima, 1985
Mouse LD50 = 352 mg/kg bw Witherup et al., Unknown date b
Guinea pig (f) LD50 = 905 mg/kg bw Witherup et al., Unknown date b
Rabbit (f) LD50 = 95 mg/kg bw Witherup et al., Unknown date b
Dermal Rabbit LD50 (24 hrs) = 1350 mg/kg Witherup and Roell, 1965
bw**
Rabbit LD50 (24 hrs) = 140 mg/kg bw Ethyl Corporation, 1975b; Hinderer,
1979
Rabbit LD50 (24 hrs) > 2000 mg/kg bw* Ethyl Corporation, 1976c
Rabbit LD50 (24 hrs) = 196.7 mg/kg bw Ethyl Corporation, 1976e; Hinderer,
1979
Rabbit LD50 (24 hrs) = 420 mg/kg bw Ethyl Corporation, 1976f; Hinderer,
1979
LD50 (24 hrs) = 795 mg/kg bw Ethyl Corporation, 1976g; Hinderer,
Rabbit
1979
Rabbita LD50 (6 hrs) = 665 mg/kg bw Witherup et al., Unknown date b
Rabbitb LD50 (24 hrs) = 135 mg/kg bw Witherup et al., Unknown date b
Intraperitoneal Rat LD50 = 23 mg/kg bw Hanzlik et al., 1980a
Rat LD50 = 6 mg/kg bw Hakkinen & Haschek, 1982
Rat LD50 = 12.1 mg/kg bw Cox et al., 1987
Rat LD50 = 4 mg/kg bw Verschoyle et al., 1993
Mouse LD50 = 138 mg/kg bw Hakkinen & Haschek, 1982
Mousec LD50 = 152 mg/kg bw Fishman et al., 1987
Moused LD50 = 999 mg/kg bw Fishman et al., 1987
Hamster LD50 = 270 mg/kg bw Hakkinen & Haschek, 1982
Subcutaneous Rat LD50 > 10 mg/kg bw Clay & Morris, 1989
Intravenous Rabbit LD50 = 6.6 mg/kg bw Witherup et al., Unknown date b
a = peanut oil vehicle m = male only
b = kerosene vehicle e = Wesson oil vehicle
c = propylene glycol vehicle f = female only
d = corn oil vehicle
* = product tested is 62% MMT in petroleum distillate
** = product tested is 10% MMT in kerosene
Methylcyclopentadienyl manganese tricarbonyl (MMT) 51
Oral LD50 values in rats range from 9 to 176 mg/kg bw MMT. The oral LD50 in rats
for 62% MMT in petroleum distillate is 175 mg/kg bw and for 10% MMT in kerosene
is 89-175 mg/kg bw.
The LC50 for the rat ranges from 220 to 247 mg/m3 for a 1 hour exposure and >2 to 76
mg/m3 for a 4 hour exposure. The LC50 for 62% MMT in petroleum distillate (1 hour
exposure) is >19.8 g/m3.
Dermal (24 h) LD50 values for undiluted MMT in the rabbit range from 140 to 795
mg/kg bw. The dermal (24 h) LD50 for 10% MMT in kerosene is 1350 mg/kg bw and
for 62% MMT in petroleum distillate is > 2000 mg/kg bw.
10.2 Irritation and corrosivity
10.2.1 Skin
Ethyl Corporation (1976d) assessed the ability of a MMT solution to act as a skin
irritant on six female New Zealand rabbits. In this study, 0.5 mL of 62% MMT in
petroleum distillate was applied as an occlusive application for 24 hours to intact or
abraded dorsal skin that had been shaved. Effects were graded when patches were
removed (24 hrs) and 24 hrs later (48 hrs) in accordance with OECD guideline 404.
MMT in petroleum distillate was found to induce skin irritation at 24 and 48 hours in
both intact and abraded skin. Erythema was scored as 1.2 and 1.0 for intact skin and 1.5
and 1.0 for abraded skin, at 24 and 48 hours respectively. Oedema was scored as 1.7
and 0.8 for intact skin and 2.3 and 1.0 for abraded skin, at 24 and 48 hours respectively.
Campbell et al. (1975) examined the skin irritancy potential of MMT in groups of six
male albino rabbits. MMT was applied under occlusion, as a neat solution (0.1 mL) to
intact or abraded dorsal skin. The covering and test solution were removed after 24
hours. Skin reactions were assessed when the patch was removed (24 hrs) and 48 hours
later (72 hrs) and were scored using an approach described by Campbell et al. (1975).
Signs of erythema and oedema were confined to the test area and no eschar formation
was observed (no further details provided). Campbell et al. concluded that MMT is not
an irritant in intact skin and is a mild irritant in abraded skin.
The ability of MMT to induce skin irritation was assessed in intact and abraded skin of
female New Zealand albino rabbits according to the method of Draize et al. (1944). In
this study MMT (0.5 mL) was applied to groups of six rabbits under occlusion for 24
hours. MMT was found to cause well-defined erythema and slight oedema in both
abraded and intact skin. Slight irritation was still present 72 hours post application.
Mean irritation scores for erythema/eschar formation and oedema were 1.29 and 1.5
respectively, averaged over 24 and 72 hours (Ethyl Corporation 1976i; Hinderer 1979).
In acute lethality dermal studies, skin reactions were also noted. MMT (112-2000
mg/kg bw) was applied to intact and abraded rabbit skin under occlusion for 24 hours.
At 24 hours post dosing, a slight to well-defined erythema and moderate oedema were
noted in most animals. Skin irritation had generally cleared by day 3 in surviving
rabbits. Each treatment group contained 4 rabbits (Ethyl Corporation 1975b, 1976f,
1976g).
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Two poorly reported studies examining skin irritation were also identified. The first
reported that undiluted MMT applied to the skin of rabbits for 24 hours caused no
remarkable signs and a 6 hour exposure of 10% MMT in peanut oil to rat skin resulted
in a mild transient irritation (Witherup et al Unknown date b). The second study found
that a 24-hour exposure to Combustion Improver No. 2 Product (10% MMT in
kerosene) caused erythema and oedema at 24 and 72 hours in rabbits (Witherup and
Roell 1965).
10.2.2 Eye
Ethyl Corporation (unknown date) assessed the ability of MMT to act as an eye irritant
on six Albino New Zealand rabbits. In this study, 0.1 mL of 62% MMT in petroleum
distillate was applied to the conjunctival sac of the right eye. Ocular reactions were
graded 24, 48 and 72 hours post application in accordance with OECD guideline 405.
Conjunctival redness was scored as 1.0, 0.167 and 0 at 24, 48 and 72 hours respectively
(mean values). Conjunctival chemosis was scored as 1.167, 0.167 and 0 at 24, 48 and
72 hours respectively. Corneal opacity and iridal lesions were not observed. Two
rabbits reportedly vocalised at instillation.
The ability of MMT to cause eye irritation was assessed also according to the grading
method of Draize et al. (1944). In this study, MMT (0.1 ml) was applied to the
conjunctival sac of the right eye of six Albino New Zealand rabbits. MMT resulted in
mild conjunctival redness but no corneal effects. Mean Draize scores on day 1 of 0.83
and 0.17 for conjunctival redness and chemosis respectively were reported. A
conjunctival discharge was observed in one animal on day 2 and one animal still
showed minor conjunctival redness (score 1) on day 3. No effects were observed from
day 4 onwards (no further details provided) (Ethyl Corporation 1976j; Hinderer 1979).
In an acute inhalation lethality study, rats receiving whole body exposure to MMT
vapours (0.108-0.309 mg/L for 1 hr or 0.047-0.1 mg/L for 4 hrs) experienced eye
irritation that lasted for a maximum of one day. Each treatment group contained 10
animals (Ethyl Corporation 1976h). Lacrimation and mild eye inflammation were
observed also for up to 30 minutes post exposure in a similar on1 hour inhalation
toxicity study of a product consisting of 62% MMT in petroleum distillate (Ethyl
Corporation 1976a).
Two poorly reported studies examining eye irritation were also identified. In the first
study, occasional mild injection of the vessels of the bulbar conjunctivae was observed
in rabbit eyes that had been exposed to 10% MMT in kerosene (Witherup et al
Unknown date b). In the second study, a 24-hour exposure to Combustion Improver
No. 2 Product (10% MMT in kerosene) resulted in a mild hyperemia in the palpebrae in
two of six New Zealand albino rabbits. Eyes were considered normal on days 2 and 3
(Witherup and Roell 1965).
10.3 Sensitisation
There are no animal studies or human case reports of skin or respiratory sensitisation to
MMT.
Methylcyclopentadienyl manganese tricarbonyl (MMT) 53
10.4 Repeated dose toxicity
In a 30-week inhalation study, mice and rats (up to 30 animals/group, sex not specified)
were exposed to between 0.0062-0.413 mg/L MMT for 7 hours per day, 5 days per
week, for up to 30 weeks. Weight loss and death were observed in animals as a result of
MMT exposure. In mice at 0.014 mg/L, the percentage weight loss reported was 26.2%
and mortality occurred in 1/10 animals. At 0.017 mg/L, weight loss increased to 35.9%
and mortality occurred in 27 of 28 mice prior to 77 exposures and in one mouse after
127 exposures. Rats exposed to 0.017 mg/L showed 10.7% weight loss with mortality
in 9 of 20 animals.
At the lower dose of 0.0062 mg/L animals gained weight and none died. Many of the
animals, including controls, died as a result of a chronic infectious disease
(pneumonitis) and were not included in the analysis.
The viscera were examined for gross pathological changes and several tissues were
examined for microscopic changes. The only findings noted in the report were that
pathological changes resulting at high MMT concentrations were observed primarily in
the liver and kidneys and at lower concentrations degenerative changes in the liver and
kidneys occurred less consistently. The NOAEL for rats and mice was 0.0062 mg/L
(6.2 mg/m3). Using the data of Gold et al (1984) as reference values for dose
calculations, assuming a respiratory volume of 6 L/hour and a (male) body weight of
0.2 kg, this NOAEL corresponds to an intermittent dose of 1.3 mg/kg bw/day in rats.
Small groups of cats (1/dose), rabbits (1-4/dose), and guinea pigs (6-9/dose) were
exposed to similar doses of MMT for 4 to 150 weeks. Very few animals died and none
died at exposures at and below 0.017 mg/L MMT for 150 weeks. Two dogs were
exposed to 0.012 mg/L MMT for 100 weeks and neither died. No MMT-dependent
toxic effects were observed in cats, rabbits, guinea pigs or dogs. This is an unpublished
study and no individual animal data or statistical analyses were reported (Witherup et al
unknown date a).
Toxicity resulting from repeated dermal exposure to 0, 0.4, 2.4 or 16 g/L MMT
(equivalent to 0, 0.8, 4.8 and 32 mg MMT/kg bw/day) in gasoline with and without
tetraethyl lead (TEL) (~ 2 g/L) was assessed in Weanling CFW rats and male New
Zealand White rabbits. Rats were exposed 5 days per week, for 25 weeks while rabbits
were exposed 5 days per week, for 14 weeks. Repeated dermal contact with the
gasoline solutions (2 mL/kg), regardless of whether they contained MMT with or
without lead, resulted in severe and extensive skin injury in rabbits. Initial gasoline
exposure caused a mild transient erythema, which developed into a mild oedema with
continued exposure. The skin eventually became dry, hard, wrinkled with numerous
fissures and ulcerations. At 4.8 and 32 mg MMT/kg bw/day, vacuolar degeneration of
the liver and kidney was observed in some rabbits. Mild skin damage was seen in rats
exposed to the gasoline solutions, regardless of whether they contained MMT with or
without lead. No neurological irritation or significant effects on mortality, body weight,
blood content (haemoglobin and leukocyte number), organ weight (heart, liver, lungs,
kidneys, brain), or the viscera could be attributed to MMT. Five male and 5 female rats
and 5 male rabbits were used per treatment. This is an unpublished report and
individual animal data and scores and statistical analysis were not reported (Witherup et
al unknown date c).
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10.5 Reproductive toxicity
The developmental toxicity of MMT was examined in COBS CD rats. Male and female
rats were mated at a 1:1 ratio. Copulation was determined by the identification of a
copulation plug, marking day 0 of gestation. Pregnant females were dosed orally with
MMT (2-9 mg/kg bw) in corn oil daily, on days 6-15 of gestation. Pregnant females
were examined daily on days 0-20 of gestation for body weight gain, toxicological
effects and mortality. Upon completion of the study (day 20 of gestation), mated
females were sacrificed; the uterus was excised and weighed. The location of viable
and nonviable foetuses, early and late resorptions, the number of total implantations
and corpora lutea, and maternal liver weights were recorded. The abdominal and
thoracic cavities, palate, and eyes of the foetuses were examined. Foetal weight, length,
and sex were recorded. Approximately one-third of foetuses were subjected to visceral
examination and the remaining foetuses for skeletal examinations.
MMT-treated females suffered from a slight increase in matting and staining of the
anogenital haircoat at 9 mg/kg bw/day. Differences in the number of maternal deaths
and pregnant dams between MMT-treated and control groups were not statistically
significant. Mean maternal body weights were slightly lower than controls at all dose
levels during gestation. Compared to controls, weight loss in animals receiving the
highest dose of 9 mg/kg bw/day reached statistical significance (p<0.01) at day 9 after
gestation. Mean maternal liver weights for MMT-treated pregnant female rats were not
significantly different from controls.
No statistically significant differences were observed between MMT-treated and
control groups in the ratio of male to female foetuses, mean number of early
resorptions, mean number of viable foetuses, or mean foetal crown-rump lengths. A
slight but significant decrease in mean foetal body weight (p<0.05) was observed only
in the 6.5 mg/kg bw/day MMT group. A statistically significant increase (p<0.05) in the
number of foetuses and litters with malformations was detected at a dosage of 9 mg/kg
bw/day MMT. At this dose, 14 foetuses (7 litters) showed malformations out of 163
foetuses (21 litters) examined skeletally. This compares with 5 foetuses (1 litter)
showing malformations out of 196 control foetuses (23 litters) examined skeletally.
The significant increase in malformations in the high dose MMT-treated group was due
to the presence of bent ribs in this group and not in controls. With the exception of a
single foetus showing microphthalmia, all other malformation endpoints were normal.
Across doses, the prevalence of bent ribs showed a dose related increase in incidence
although a dose relationship was not evident for other malformation endpoints. The
authors argue that bent ribs are not regarded as a usual malformation and that the
exclusion of other malformation endpoints suggests a lack of a teratogenic response.
Maternal weight losses at the highest MMT dose are evidence of minor maternal
toxicity. Historical control data provided in this study show both microphthalmia and
rib anomalies as spontaneous events in this species. Given this history of spontaneous
rib anomalies, an association between maternal toxicity and delayed ossification and
the uncertainty over whether delayed foetal growth in possible association with
maternal toxicity constitutes embryofoetotoxicity (Guittin, El閒ant and Saint-Salvi,
2000), data are insufficient to consider the prevalence of bent ribs alone as indicating
abnormal enbryogenesis.
The NOAEL for maternal and developmental toxicity was 9 mg/kg bw/day. Twenty-
five mated female rats were used in each treatment group (Ethyl Corporation 1979a).
Methylcyclopentadienyl manganese tricarbonyl (MMT) 55
The developmental toxicity of MMT was also examined in Long-Evans rats. Males and
female rats were mated nightly at a 1:1 ratio. Vaginal smears were taken each morning
and examined for the presence of sperm or a vaginal plug. The day mating was
observed was considered day 0 of gestation. Pregnant females (9-59 animals per dose
level) were dosed daily by gastric intubation with MMT (0, 5, 10, 20 and 40 mg/kg bw)
in corn oil on days 6-15 of gestation.
Maternal body weight gain was significantly reduced during treatment on gestation
days 6-15 in all MMT treatment groups. Weight gain was similar for the MMT-treated
groups and controls by day 21 of gestation. MMT-treated females suffered from
epistaxis, irregular or rapid breathing, and urinary incontinence during the treatment
period. In addition to these symptoms, females exposed to 20 or 40 mg/kg bw/day were
cachectic, dehydrated, lethargic with some alopecia and pilo-erection. Maternal death
rates were comparable to controls at doses of 5 and 10 mg/kg bw/day but were
increased significantly at the two highest dose levels, with mortality observed in 41 of
59 rats receiving 20 mg/kg bw/day and mortality after initiation of dosing in rats
receiving 40 mg/kg bw/day leading to termination of this dose group. All deaths at 40
mg/kg bw/day occurred within 1-5 days of the treatment (days 7-11 of gestation).
Examination of the animals in the high dose group revealed that lungs were mottled
(5/9), dark red (6/9) and firm (5/9), the trachea contained a foamy liquid (3/9), and
livers were dark red (3/9).
At 20 mg/kg bw/day, a significant decrease in maternal pregnancy rate was observed
accompanied by significant decreases in fetal viability. At this dose, fetuses showed
significant increases in soft tissue malformations, skeletal malformations and
ossification variations.
At 5 mg/kg bw/day, in addition to significantly decreased maternal body weight gains,
a significant increase in fetuses with skeletal malformations (total 7.4%, p<0.05) and
ossification variations (total 47%, p<0.05) was recorded. This incidence of skeletal
malformations at this dose was attributable predominantly to increased observations of
curly tail. However, these findings were not supported by external fetal examination at
term sacrifice, were not seen at the higher dose of 10 mg/kg bw/day and so were
considered of uncertain toxicological significance.
Skeletal malformations observed in MMT-treated fetuses especially at the highest dose
of 40 mg/kg bw/day included derangement of ocular pigmentation, curly tail and
vertebral defects (missing or fused ribs).
The incidence of soft tissue malformations in MMT-treated fetuses was comparable
between controls and 5 and 10 mg/kg bw/day dose groups. Soft tissue malformations
observed especially in the 40 mg/kg bw/day dose group included microphthalmia,
anophthalmia and distended ureter.
The NOAEL for developmental toxicity was determined as 10 mg/kg bw/day with
effects seen at the maternally toxic dose of 20 mg/kg bw/day (Ethyl Corporation
1978a).
In a separate study by Ethyl Corporation (1979b), pregnant female Sprague-Dawley
rats (5 per dose group) were treated daily with a single oral dose of MMT (1-30 mg/kg
bw/day) on days 6-15 of gestation. Several females treated with 10 or 30 mg/kg bw/day
and most treated with 20 mg/kg bw/day showed ocular discharge and matting and
staining of the anogenital region. One female receiving 10 mg/kg bw/day died on
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gestation day 11, four rats treated with 20 mg/kg bw/day and all treated with 30 mg/kg
bw/day died between days 7-10 of gestation. Most of the rats that died during the study
had congestion of the lungs and liver. A moderate reduction in body weight was
observed in females treated with 10 mg/kg bw/day. The reduction in weight gain at 20
mg/kg bw/day was described as severe. Between 1-10 mg/kg bw/day a small increase
in the mean number of early resorptions was observed. At 1 and 10 mg/kg bw/day a
slight decrease in the mean number of implantations and live fetuses was noted. The
one surviving female from the 20 mg/kg bw/day was gravid at day 20 of gestation. No
individual animal data or statistics were provided. Insufficient data were provided to
establish NOAELs and LOAELs.
10.6 Genotoxicity
The genotoxicity of MMT was investigated in vitro on Salmonella typhimurium strains
TA98, TA100, TA1535, TA1537, TA1538 and Saccharomyces cerevisiae strain D3.
MMT was tested at 1, 10, 50, 100, 500, 1000, 5000 礸/plate for the S. typhimurium
strains and 0.1-5% for S. cerevisiae in the presence and absence of a metabolic
activator (Aroclor 1254-stimulated rat liver homogenate). Cytotoxic effects were
observed in all S. typhimurium strains tested at MMT concentrations between 500-5
000 礸/plate. In the presence of the metabolic activator, MMT when tested at 0.1-1%
was found to reduce the survival of S. cerevisiae by approximately 50%. The survival
of S. cerevisiae was doubled in the presence of 5% MMT and reduced at lower doses,
in the presence of metabolic activator. MMT did not result in a significant increase in
the average number of S. typhimurium histidine revertants per plate or S. cerevisiae
mitotic recombinants (Ethyl Corporation 1977b).
MMT was also investigated in vitro in a chromosome aberration study using Chinese
hamster ovary (CHO) cells and in vivo in a micronucleus assay using C57B1 mice.
MMT induced chromosomal aberrations in vitro but did not induce effects in vivo
(Blakey, 1996, personal communication).
A dominant lethal study was conducted on CD-1 mice. Sexually competent males were
dosed via gastric intubation with MMT (80 and 160 mg/kg bw) in corn oil daily, for 5
consecutive days. On the last day of the treatment period, at least two hours after the
last dosing, three untreated virgin females were placed with each male. Male and
females remained together for seven days and then the females were removed and
replaced with three new untreated virgins. This procedure continued for eight weeks.
Males were observed daily for evidence of pharmacologic and toxicologic effects and
mortality during both the exposure period and during mating. Females were sacrificed 8
days after removal from the male and the number of uterine implantations were
recorded. Implantations were distinguished as early resorption sites (early fetal death),
late resorption sites (late fetal deaths) and viable fetal swellings. During days 1 to 3 of
the exposure period, male mice showed signs of hypoactivity, dehydration, and
lacrimination. The male mortality rate at 80 mg/kg bw/day was 17% (2/12) and 23%
(3/13) at 160 mg/kg bw/day. All males that died during the exposure period did so on
day 3 or 4 of the treatment. Mottled liver (2/5), bright red lungs (1/5), bladder (1/5) and
thoracic cavity abnormalities (1/5) were observed in the deceased males.
The pregnancy rate of the MMT groups was similar to controls. There was no
statistically significant difference in the mean number of early fetal deaths or viable
fetal swellings per pregnant female between the negative control and MMT-treated
groups. An exception occurred in week three where 80 mg/kg bw/day MMT treatment
Methylcyclopentadienyl manganese tricarbonyl (MMT) 57
resulted in an increase in the mean number of viable fetal swellings per pregnant
female. Expressed as a percentage of total implantation sites, early fetal death data were
comparable between negative controls and MMT-treated groups. Exceptions were a
significant decrease at week three for the 80 mg/kg bw/day MMT treatment and a
significant increase at week seven for 160 mg/kg bw/day MMT treatment. These
deviations from negative controls were not considered biologically significant. Ten
male and 240 female mice were used per treatment. Negative and positive controls
(corn oil alone and triethylenemelamine respectively) behaved accordingly. Under the
conditions of the study, MMT did not cause dominant lethal effects in mice (Ethyl
Corporation 1977a).
10.7 Carcinogenicity
The effect of MMT on lung tumour development was assessed by Witschi et al. (1981)
in female A/J mice. Sixty mice were injected IP with 500 mg/kg bw urethan and sixty
with 0.9% sodium chloride. One week later 30 mice from each group were given IP
injections of MMT (80 mg/kg bw) in oil once a week for six weeks. The remaining 60
mice received corn oil alone. All mice were sacrificed 4 months after the first urethan
injection. MMT alone or when administered repeatedly after urethan or sodium
chloride treatment did not enhance lung tumour formation (Table 13).
Table 13. Tumour Incidence in MMT Treated Mice
Initial Weekly injections Percentage of Number of Number of
treatment mice with tumours per mice with
tumours (%) mouse tumours
Urethan MMT + corn oil 100 7.6 ?0.6 23
Urethan Corn oil 100 8.3 ?0.5 27
NaCl MMT + corn oil 11 0.1 ?0.1 24
NaCl Corn oil 13 0.2 ?0.1 27
The report states that lung cell proliferation, as measured by thymidine incorporation
into DNA, was reduced on day one after MMT treatment, increased by 200% above
controls on day 2, was 50% higher on day 4 and normal after day 6 (no further details
were provided).
10.8 Pulmonary toxicity
As a result of evidence of lung damage in early reports of MMT toxicity, studies
specifically examining pulmonary effects resulting from MMT exposure in animals
have been conducted. These confirm the lungs as a target organ for MMT toxicity with
common features of parenchymal inflammation, haemorrhaging and damage to
nonciliated bronchiolar epithelial (Clara) cells.
Hanzlik et al. (1980a) investigated the pulmonary toxicity of MMT in male Sprague-
Dawley rats. Single oral dosing with 125 mg/kg bw MMT (in corn oil) resulted in
haemorrhage and alveolar and perivascular oedema of the lung after 24 hours. An
accumulation of proteinaceous material in the alveoli characterised the alveolar
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oedema. Lung weight, a measure of pulmonary toxicity, was significantly elevated 24
and 72 hours after oral dosing of MMT (125 mg/kg bw) and 8/14 rats died within 24
hours. The lungs of the deceased rats showed extensive haemorrhaging and congestion.
There were minor lesions in the liver and kidneys. Lung weight was also significantly
elevated 24, 48, and 72 hours after IP injection of MMT (20 mg/kg bw) in corn oil. Pre-
treatment with phenobarbital (60 mg/kg bw for 3 days) protected against the pulmonary
toxicity of MMT but induced mildly increased plasma GPT and decreased liver G6P
indicating liver damage. The authors postulate that the protective effect of
phenobarbital may be due to a first-pass effect where an enlarged, metabolically-
induced liver limits the amount of MMT entering the systemic circulation. Between 3
and 14 animals were used per treatment.
The effect of MMT on Clara cells was examined after a single IP injection to female
BALB/C mice (120 mg/kg bw), female S/A albino rats (5 mg/kg bw) and female
LV6/LAK Syrian hamsters (180 mg/kg bw). The incorporation of radiolabelled
thymidine into pulmonary DNA, as a measure of cellular proliferation, was found to
decrease slightly one day post MMT administration in mice and hamsters. All species
showed a significant increase in thymidine incorporation by day 2, with peak
incorporation at day 2 in rats and hamsters and day 4 in mice. Labelling indices in rats
and mice, as determined by cell kinetic studies, demonstrated a significant increase in
bronchiolar and parenchymal indices at day 2. Interstitial pneumonitis characterised by
interstitial thickening and infiltration by neutrophils and macrophages, was observed in
all animals two days post MMT injection but all were found to clear by day 21. With
respect to interstitial pneumonitis, rats were the most sensitive species to MMT
treatment, followed by mice, and then hamsters. Clara cell necrosis was evident in all
species one day post MMT administration. This effect was greatest in distal airways
and was most severe in mice, which had failed to return to normal by day 21.
Bronchiolar morphology had returned to normal by day 7 in the hamster and day 21 in
the rat. In addition, necrosis of the tubular epithelium in the renal cortex was observed
in mice and minimally in the other species on days 1 and 2 post MMT administration.
The number of animals per treatment totalled 36 for mice and 18 for rats and hamsters
(Hakkinen and Haschek 1982).
The effect of MMT on Clara cells was also examined after a single IP injection to
female BALB/C mice (120 mg/kg bw) and male Fischer-derived rats (8.4 mg/kg bw).
Histopathological analysis 24 hours post MMT injection revealed a selective necrosis
of Clara cells, particularly at terminal bronchioles. Mice were found to be more
sensitive than rats. The pulmonary toxicity of MMT (90 mg/kg bw) was also assessed
in female mice after a 1 hour pre-treatment with piperonyl butoxide, an inhibitor of the
mixed-function oxidase system. The pre-treatment was found to significantly enhance
the toxicity of MMT. Clara cell damage extended into the larger bronchioles and
moderate oedema, inflammation and localised haemorrhaging became apparent within
the parenchyma. In addition, the incidence of mortality was increased. The number of
animals used per treatment was not stated (Haschek et al., 1982).
The ability of oxygen to enhance the pneumotoxic effects of MMT was investigated by
Hakkinen et al. (1983) in female BALB/C mice and female CD/CR rats. Animals were
injected IP with MMT in corn oil (5 mg/kg bw for rats and 120 mg/kg bw for mice) and
immediately dosed with either 80% oxygen or air for 6 days. Total lung hydroxyproline
levels were unaffected by MMT in mice 3 weeks after MMT dosing. A significant
increase in total lung hydroxyproline was observed in treated mice when MMT was
combined with oxygen treatment. The lungs of these mice were found to contain
Methylcyclopentadienyl manganese tricarbonyl (MMT) 59
scattered areas of interstitial thickening characterised by a mild hypercellularity and
fibrosis, located mainly at terminal bronchioles and alveolar ducts. Although MMT was
found to significantly increase total lung hydroxyproline levels in rats 3 weeks post
MMT dosing, this effect was not enhanced by oxygen. Fibrosis noted in the lungs of
rats exposed to both MMT and oxygen was similar in rats treated with only MMT.
Between 8-10 mice and 4-6 rats were used per treatment (Hakkinen et al., 1983).
The toxicity of MMT was examined in male CD rats 1.5-96 hours after subcutaneous
administration of a single dose of MMT (4 mg/kg bw in propylene glycol). Pulmonary
lavage protein levels were used as an indicator of pulmonary toxicity. Pulmonary
lavage protein levels were significantly elevated at all time points examined with levels
peaking (5-fold increase) indicating maximal pulmonary toxicity at 24-48 hours after
MMT administration. Pulmonary Mn levels peaked 3-6 hours post injection. Plasma
urea and sorbitol dehydrogenase levels were not significantly altered by MMT,
indicating little or no hepatic or renal injury. The number of animals used per treatment
was not stated (McGinley et al., 1987).
Cox et al. (1987) examined the pulmonary toxicity of MMT in male Sprague-Dawley
rats. A single IP injection of MMT (6-37.4 mg/kg bw) resulted in extensive mottling,
haemorrhage and distension of the lungs and the presence of a pink, frothy,
serosanguineous liquid in the trachea. Four animals were used per treatment.
A single subcutaneous injection of MMT (4 or 10 mg/kg bw) in corn oil vehicle to male
Sprague-Dawley rats resulted in significant pneumotoxic responses. No deaths were
observed at the lower dose. At the highest dose, 1/6 of the rats died within 24 hours.
Laboured breathing prior to death and the presence of a frothy fluid in the trachea at
necropsy were observed. Hepatic and renal markers (plasma lactate dehydrogenase,
sorbitol dehydrogenase, and blood urea nitrogen) were considered normal. The lavage
fluid of rats surviving for 24 hours after MMT administration (10 mg/kg bw) contained
increased lactate dehydrogenase, albumin and total protein. These results correlate well
with increased lung Mn content resulting from MMT administration (See Section 9).
An additional experiment was performed assessing pneumotoxic responses resulting
from MMT (4 mg/kg bw) administration in the presence of piperonyl butoxide, a
cytochrome P450 monooxygenase inhibitor. A 1-hour pre-treatment with piperonyl
butoxide (400 mg/kg bw) was found to protect against increases in lavage albumin and
reduce the levels of Mn in the lungs. Pulmonary nonprotein sulfhydryl levels were
significantly increased 24 hours after administration of MMT at 4 mg/kg bw, but this
effect was reduced by piperonyl butoxide. The level of pulmonary thiobarbituric acid
reactive materials was not altered by MMT. Heptane extraction of lung homogenates
from MMT-treated rats indicated less than 2% of the pulmonary Mn was extractable,
suggesting the presence of metabolites as opposed to MMT. Furthermore, the decrease
in pneumotoxicity in the presence of piperonyl butoxide suggests that cytochrome P450
dependent monoxygenase metabolites are responsible for toxicity. Each treatment
group contained 4-9 animals (Clay and Morris 1989).
The pneumotoxicity of MMT in female LAC-P Wistar rats was investigated after a
single IP injection (6 mg/kg bw in oil). Lung weight and the activity of -
glutamyltranspeptidase and alkaline phosphatase in bronchoalveolar lavage fluid were
quantified as measures of pulmonary toxicity. The lung wet weight of MMT-treated
rats was approximately twice that of the controls at 3-5 days post administration. MMT
also resulted in a significant increase in the activity of the bronchoalveolar lavage fluid
enzyme alkaline phosphatase 24 hours post administration. Pneumotoxic effects
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consisted of a loss of type I pneumocytes, proliferation of type II cells and macrophage
infiltration. Inhibitors of the cytochrome P-450 2B isoenzyme (O,O,S-
trimethylphosphorodithioate, bromophos, 2,4-dichloro(6-phenylphenoxy)ethylamine
and p-xylene) protected against the pulmonary toxicity of MMT. Five animals were
used per treatment (Verschoyle et al., 1993).
The effect of MMT on Clara cells of the small airways was investigated in Sprague-
Dawley rats. Each experimental group consisted of six rats. In this study rats were
sacrificed 24 hours after a single IP injection of MMT (5 mg/kg bw). The lungs were
lavaged and bronchoalveolar lavage fluid (BALF) was isolated and analysed for
biochemical markers. MMT was found to cause a significant decrease in 16-17 kDa
Clara cell protein (CC16) in BALF and a significant increase in albumin content. MMT
did not alter the serum concentration of CC16 or renal function parameters (serum
creatinine and albuminuria). However, the concentration of CC16 in urine was
significantly increased. Histopathological analysis of the lung parenchyma revealed a
slight interstital thickening and mild oedema in the alveolar walls and perivascular
connective tissue. An increase in the numbers of enlarged type II pneumocytes and
alveolar macrophages were observed in the alveolar lining and alveolar spaces
respectively. The number and activity of neutrophils and lymphocytes appeared normal.
Although ciliated cells of the epithelial lining of bronchioles appeared normal, Clara
cell necrosis was evident, especially in distal airways (Halatek et al., 1998).
10.9 Neurotoxicity
Studies specifically examining the neurotoxicity of MMT in animals have been
conducted. These indicate the ability of MMT to induce seizure activity and brain
neurotransmitter and enzyme imbalances.
The ability of MMT to induce neurotoxic effects was investigated in male CD-1 mice
injected subcutaneously with MMT (10, 20 or 80 mg/kg bw in propylene glycol). The
concentration of dopamine in the striatum of mice that received MMT at 20 and 80
mg/kg bw on alternate days for 3 weeks (total of 11 injections) was reduced by 10%
and 23% respectively. The level of dopamine in the olfactory tubercle was also
significantly reduced in mice receiving 80 mg/kg bw. MMT at 80 mg/kg bw increased
4-aminobutyric acid (GABA) levels in both the striatum and olfactory tubercle but not
the cerebellum. MMT did not significantly alter the activity of choline acetyltransferase
in the striatum, substantia nigra, hippocampus or cerebral cortex. There was no
significant change in dopamine or GABA levels in mice that received a single 80
mg/kg bw MMT injection when examined 1 and 21 days post injection. Between 6 and
16 animals were used per treatment (Gianutsos and Murray 1982).
Yong et al. (1986) investigated the neurotoxic effects in female Wistar rats resulting
from repeated subcutaneous injections of MMT in propylene glycol. Rats received
either 24 injections over a 48-day period and were sacrificed 24 hours after the last
injection or 75 injections over a 5-month period and sacrificed one month after the last
injection. The first MMT injection was given at 5 mg/kg bw, the second at 10 mg/kg
bw, the third 15 mg/kg bw, the fourth 25 mg/kg bw, and the remainder at 50 mg/kg bw.
The concentration of Mn in the cerebellum of rats surviving to 24 hours after the last of
24 injections was approximately twice that of controls (4.59 verses 1.71 礸/g dry
weight). One month after the last of 75 MMT injections the level of Mn in rat
cerebellum was only slightly increased above controls. Although 3,4-
dihydroxyphenylacetic acid (DOPAC) levels in the striatum were slightly depressed in
Methylcyclopentadienyl manganese tricarbonyl (MMT) 61
rats that received 24 MMT injections, tyrosine hydroxylase activity and dopamine and
homovanillic acid (HVA) levels were considered normal. All neurological markers
examined in rats that received 75 injections were similar to controls. Histological
analysis of the zona compacta of the substantia nigra indicated that the numbers of
perikarya per unit area in rats that received 75 MMT injections were similar to controls.
Between 8 and 13 rats were used per treatment.
The neurotoxicity of MMT was assessed in male CD-1 mice after a single IP injection
of MMT (100-2000 mg/kg bw in propylene glycol or corn oil). Each treatment group
contained between 4 and 6 animals. In animals that died, death was seizure-related and
occurred within 2 hours of MMT administration. Seizure activity was observed within
0.5-1.5 min post MMT administration. MMT-induced seizure activity was
accompanied by a 2.5-fold increase in brain Mn concentrations. The Mn brain content
of control mice was 0.9 礸/g. The brain Mn content of mice demonstrating seizure was
2.45 礸/g when MMT was administered in propylene glycol and 3.25 礸/g when MMT
was administered in corn oil. Only a small increase in brain Mn concentrations was
observed in MMT-treated mice that did not show seizure activity (1.14 礸/g for
propylene glycol and 1.63 礸/g in corn oil). The synthesis and release of GABA was
unaffected 30 min after animals were injected with MMT (25-50 mg/kg bw) and
aminooxyacetic acid (AOAA) (20 mg/kg bw, ip) to inhibit GABA transaminase. MMT
was found to inhibit the binding of t-butylbicycloorthobenzoate (TBOB), a ligand for
the GABA-A receptor linked chloride channel, to mouse brain membranes (median
inhibitory concentration (IC50) = 22.8 礛) suggesting that seizure activity of MMT
may be linked to inhibitory action at this site (Fishman et al., 1987).
The neurotoxicity of MMT was assessed in male ddY mice after chronic oral
administration of MMT in food (0.5 g Mn/kg food) for 12 months. Between 4 and 6
animals were used per treatment. Daily food intake per mouse was reported as 3.6 ?0.9
g for controls and 3.1 ?0.7 g in the MMT-treated group. The dosage was therefore
equivalent to approximately 51.7 mg Mn/kg bw/day (208.5 mg MMT/kg bw/day).
MMT-treated mice showed significant weight loss compared to controls during the 12-
month treatment period. Spontaneous motor activity was measured over a 30 minute
period at intervals during the 12-month exposure period. The level of spontaneous
motor activity was similar for the control and MMT-treated groups throughout the
study, except on day 80, when the MMT-treated group showed significantly more
motor activity compared to controls (Komura and Sakamoto 1992).
Although the MMT dose in this study are of similar magnitude to oral LD50 values for
MMT in mice (Section 10.1), no deaths were reported in this study. This suggests a
likely greater tolerance of a gradual MMT and Mn intake in food compared to a similar
amount as a bolus dose.
In what appears to be a further study of the above animals, effects of MMT on various
brain biogenic amines were reported by Komura and Sakamoto (1994). At the end of
the exposure period the concentration of normetanephrine in the cerebellum of MMT-
treated mice was significantly increased (46 ?8 ng/g wet wt) when compared to the
control group (6 ?1 ng/g wet wt). This effect correlated with a significant increase in
Mn levels in the cerebellum (0.29 礸 Mn/g ww versus 0.13 礸 Mn/g ww). Additional
alterations were observed in brain biogenic amine levels but these effects did not
correlate significantly with an increase in Mn. For example, the concentration of
norepinephrine was significantly decreased and homovanillic acid was significantly
increased in the corpus stratum; 3-methoxytyramine was significantly increased in the
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midbrain; 3,4-dihydroxyphenylacetic acid was significantly decreased in the
cerebellum; 3,4-dihydroxyphenylacetic acid, homovanillic acid, and serotonin were
significantly decreased in the medulla oblongata and metanephrine was significantly
increased in the medulla oblongata. The concentration of Mn in the corpus striatum,
hypothalamus, midbrain, cerebral cortex, hippocampus and medulla oblongata was
similar in MMT-treated and control groups (Komura and Sakamoto, 1994).
Evidence of neurotoxicity has been reported in ICR mice treated with MMT. Mice were
injected IP daily with 0.05 or 0.1 mg/g bw MMT in corn oil for 3 days. Between four
and six animals were used per treatment. Each treatment group contained between 4
and 6 animals. Both doses of MMT were found to significantly decrease motor nerve
conduction velocity and reduce ouabain-sensitive Na+K+-ATPase activity in the sciatic
nerve in vivo. MMT (0.03-3 mM) did not affect the activity of sciatic nerve Na+, K+-
ATPase in vitro. The reduced ATPase activity correlated with a 58% decrease in the
amount of catalytic 1 subunit polypeptide. These effects were associated with
significantly increased Mn concentrations in blood and sciatic nerve of MMT-treated
mice. These results suggest that MMT-induced neuropathy is associated with reduced
nerve Na+, K+-ATPase activity and motor nerve conduction velocity (Liu et al 2000).
The mechanisms of MMT neurotoxicity have also been studied in vitro. In a recent
study of cultured dopamine-producing PC-12 cells and nondopaminergic striatal -
aminobutyric acidergic M213-20 cells, MMT was shown to be acutely cytotoxic
particularly to dopamine-producing cells and decreased intracellular dopamine levels.
Generation of intracellular reactive oxygen species (ROS), an early effect in toxicant-
induced apoptosis, was observed within 15 minutes of exposure. A hallmark of
apoptosis, genomic DNA fragmentation, was induced in a concentration dependent
fashion. Lastly, PC-12 cells overexpressing the apoptosis inhibitory molecule Bcl-2
were shown to be significantly refractory to MMT-induced ROS. These in vitro data
indicate that oxidative stress plays an important role in mitochondrial-mediated
apoptotic neuronal death after exposure to MMT (Kitazawa et al., 2002).
10.10 MMT combustion products
Several studies exist examining the toxicity of combustion products of MMT generated
either via a propane flame or from the operation of an automotive engine.
The chronic inhalation toxicity of Mn oxide (Mn3O4) as a combustion product of MMT
was the subject of a report (Rinehart, 1975) published subsequently by Ulrich et al.
(1979 a,b,c).
Ulrich et al. (1979a) documented the experimental procedure to examine the chronic
inhalation toxicity of MMT combustion products. MMT combustion products, `similar
to that produced by an internal combustion engine', were generated by burning MMT
vapours in a propane flame. This method was reported to produce a particulate matter
consisting of Mn oxide (Mn3O4) with an aerodynamic diameter of approximately
0.11祄.
Using the experimental procedure published by Ulrich et al. (1979a), monkeys and rats
were exposed to Mn oxide (Mn3O4) aerosol produced by the combustion of MMT. The
animals were exposed for 24 hours per day for nine months to 0, 11.6, 112.5 or 1152 礸
Mn/m3 as Mn oxide (Mn3O4) aerosol. Each treatment group contained 15 male and 15
female rats and 4 male and 4 female monkeys. No clinical signs of toxicity were
Methylcyclopentadienyl manganese tricarbonyl (MMT) 63
observed at the end of the exposure period. Weight gain was normal in all monkeys,
while rats exposed to 1152 礸 Mn/m3 as Mn oxide exhibited an accelerated weight
gain. Monkeys in the highest dose group had increased levels of haemoglobin, mean
corpuscular haemoglobin, and mean corpuscular haemoglobin concentration. The mean
corpuscular haemoglobin level was also increased at 112.5 礸 Mn/m3 as Mn oxide. At
the highest dose, rats exhibited increased haemoglobin, erythrocytes, mean corpuscular
haemoglobin concentration and a decrease in mean corpuscular volume. At the same
dosage male rats also showed increased mean corpuscular haemoglobin. At 112.5 礸
Mn/m3 as Mn oxide, male rats showed decreased reticulocytes and leukocytosis, while
females exhibited decreases in hematocrit, haemoglobin, mean corpuscular
haemoglobin and mean corpuscular volume. The authors state that while the effects
were statistically significant, they may be within an acceptable normal range. All
effects were reversible, as demonstrated by normal values at 6-months post exposure.
Clinical chemistry evaluations revealed that at 1152 礸 Mn/m3 as Mn oxide male rats
were found to have a depressed serum phosphate level. Microscopic evaluations
revealed that brain, sternal bone marrow, and lung tissue were free of any changes. A
small increase in liver weight was observed in female rats at 1152 礸 Mn/m3 as Mn
oxide. The weight of other major organs was considered normal (Ulrich et al., 1979b).
In a follow-up publication by Ulrich et al. (1979c), the effect of MMT combustion
products on pulmonary function was reported in each treatment group containing 15
male and female rats and 4 male and female monkeys. With regard to pulmonary
function, there was a significant but small increase in tidal volume in male monkeys
that received 112.5 礸 Mn/m3 as Mn oxide. Apart from this effect pulmonary function
was considered normal. Although 14/112 electromyographic and limb tremor
oscillograph records demonstrated possible abnormalities, the abnormal findings were
evenly distributed between the dosage groups suggesting there were no exposure
related effects (Ulrich et al., 1979c).
The toxicity of MMT combustion products was also tested via exposure of 180 male
golden hamsters and 370 male outbred albino rats to automotive emissions generated
using a 1972 Chevrolet 350 CID engine dynamometer system. Emissions were derived
by passing exhaust generated from the combustion of fuel consisting of indolene
"clear" containing MMT at 0.25 g Mn/gallon through a muffler, followed by dilution
(25:1) with clean conditioned air. The final diluted emissions were split in two with one
half being irradiated prior to exposure to animals. Irradiated emission typically
contained 855 礸/m3 particles (0.29 祄) consisting of 117 mg/m3 Mn (13.7%).
Nonirradiated emission typically contained 635 礸/m3 particles (0.26 祄) consisting of
131 mg/m3 Mn (20.7%). Animals were exposed for 8 hours per day for 56 consecutive
days. Animals were sacrificed and tissues were collected for histological evaluation and
Mn analysis. Alterations in general condition, appearance and weight gain were not
observed. Hamsters were deemed to be free of abnormalities at necropsy while chronic
respiratory disease lesions were observed in rats. Lesions observed in the lung consisted
of a thickened, cuboidal epithelium at the terminal bronchiole that extended partly
down the respiratory tree. These changes were noted in 21%, 14%, and 6% of
irradiated, nonirradiated and control animals respectively. The degree of severity of the
lesions did not appear to increase with exposure duration. A chronic hepatitis around
portal triads was also observed. Manganese levels in the tissues (brain, liver and lung)
of exposed animals were generally higher than controls (Moore et al., 1975b).
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10.11 Human exposure
No epidemiological data are available. The following few overseas incidents of human
exposure are described briefly in the Ethyl Corporation Medical Guide for Use by
Companies Handling HiTEC 3062 Octane Booster (Ethyl Corporation, 2000).
Ethyl Corporation reported an incident of acute exposure to MMT. Three workers were
reportedly exposed to an unknown concentration of airborne MMT for a short period
and two workers were sprayed with the material. Symptoms reported included burning
of the skin, a metallic taste in the mouth, headache, nausea and chest tightness. These
effects abated within 24-48 hours.
Four workers were reportedly exposed to MMT in an 18 x 20 foot room when
approximately 25 gallons (half a drum) of neat MMT was poured into a large open
steam-heated pot. The MMT was heated long enough to form vapours as the workers
detected an unusual odour within 5 minutes, when they shut off the heat and left the
building. The four workers were examined immediately and no adverse effects or
symptoms were noted. No symptoms were also reported 24 hours post exposure. Three
hours post exposure the urine of the four workers contained 23, 87, 20, and 10 礸
Mn/L. Twenty three hours post exposure urine levels had dropped to 8, 22, 5, and 10 礸
Mn/L and workers were still free of symptoms.
Six individuals who reportedly experienced a 30 min skin exposure to MMT all
reported a burning sensation of the skin and metallic taste in the mouth. Other
symptoms included headache (4/6), nausea (4/6), gastrointestinal upset (3/6), dyspnea
(3/6), chest tightness (1/6) and paresthesia (1/6). All symptoms appeared within 5-60
min post exposure and had abated in four individuals within 2-4 hours. The remaining
two individuals reported that abdominal distress lasted for 2 days.
In 1959, two men wearing rubber gloves and air masks were exposed to a fine spray of
neat MMT caused by a leak during a pumping operation. Although the hands and face
of the two workers were covered, the spray moistened the remainder of both workers
bodies for approximately 1.5 hours. The socks and shoes of both workers were
saturated. On examination, the two men complained of a slight burning of the skin.
Blood parameters and muscular co-ordination were unaffected. On the day of the
exposure, urine Mn levels of the two workers were 137 and 46 礸/L. Several weeks
later urine Mn levels were 3.4 and 2.9 礸/L.
A small volume of MMT, reportedly 5-15 mL when spilt on the wrist of a worker
caused "thick tongue", giddiness, nausea and headache within five minutes (U.S. Navy,
1968).
Methylcyclopentadienyl manganese tricarbonyl (MMT) 65
11. Pharmacokinetics and Toxicity of
Manganese
Normally, MMT in fuel is destroyed during combustion resulting in the formation of
inorganic Mn compounds. In early studies, MMT was reported to combust
predominantly to Mn tetraoxide. More recent tests indicate combustion also to Mn
phosphate and Mn sulphate with lesser oxides at higher oxidation states. Given
particulate inorganic Mn emissions resulting from MMT use and that Mn is likely to
reach target organs, it is prudent that a review of MMT as an AVSR should include a
toxicological review of Mn.
Manganese is found in rock, soil, water and air and constitutes 0.1% of the Earths crust
(NAS 1973). Manganese is generally not found as a base metal but is present as a
variety of compounds such as oxides, sulphides, chlorides, carbonates, silicates,
sulphates, nitrates and borates (NAS 1973). Different salts of Mn have a wide range of
solubilities and are absorbed through biological membranes at different rates. Elemental
Mn can exist in seven oxidation states depending on the compound, the majority of
environmental Mn exposures being to Mn (II) and Mn (IV).
Atmospheric Mn is produced primarily from industrial emissions as particulate matter,
with a mass median equivalent diameter of less than 5 祄, 50% of which is smaller
than 2 祄 (USEPA 1984; WHO 2000). Average airborne concentrations of Mn range
from ~0.5-14 ng/m3 in remote locations, to ~40 ng/m3 in rural areas, and ~65-166 ng/m3
in urban locations. Airborne Mn concentrations can rise to ~8000 ng/m3 in source-
dominated areas such as foundries (USEPA 1984; Stokes et al., 1988). WHO (1981)
has estimated the mean daily intake of Mn from air in the general US population is less
than 2 礸/day. This rises to 10 礸/day (24 h peak values exceed 100 礸/day) for
individuals living near industrial areas that utilise Mn.
Exhaustive reviews of Mn and Mn compounds have been conducted in "Toxicological
Profile for Manganese (Update)" (ATSDR 2000) and the Concise International
Chemical Assessment Document 12 ?"Manganese and Its Compounds" (WHO 1999).
The following toxicological information is based primarily on this latter document.
11.1 Kinetics and metabolism
Manganese is an essential element and part of a normal diet of humans and animals. It
plays a role in protein and energy metabolism, metabolic regulation, bone
mineralisation, nervous system function and free radical neutralisation. Manganese is
absorbed in the gastrointestinal tract after ingestion and also across the alveoli of the
lungs after inhalation of Mn-containing dust or fumes. Manganese is transported in the
plasma by transferrin, can cross the blood-brain barrier and placenta and tends to
concentrate in the brain as well as tissues rich in mitochondria, such as the liver and
kidney (WHO 1981). Dermal uptake of Mn or inorganic Mn compounds is considered
extremely limited in the absence of an absorbable solvent. Dietary Mn intake is an
important exposure route. In humans, the fraction of Mn absorbed in the
gastrointestinal tract is variable but is in the order of 3-5%. The extent of absorption via
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inhalation is determined by particle size and the location of pulmonary deposition.
Particles of sufficiently small size to deposit in the lower airways are likely to be
absorbed whilst larger particles confined to the upper airways may be transported
vertically to the throat via the mucociliary elevator then swallowed and absorbed in the
gastrointestinal tract.
Absorption of inorganic Mn compounds is dependent on the route of exposure as well
as the chemical species. For example, in rodents, absorption of Mn chloride as
measured by Mn levels in blood and brain occurs readily via oral, intraperitoneal or
intratracheal routes. In contrast, while Mn dioxide is also absorbed significantly via
intraperitoneal or intratracheal routes, poor absorption occurs via the oral route. Also,
highly elevated Mn levels in the brain follow intratracheal but not oral administration of
either Mn species. Single dose kinetic studies also show that Mn chloride is absorbed
rapidly particularly via the intratracheal route compared to the oral route whereas Mn
dioxide is absorbed relatively slowly. Also, although pulmonary clearance rates
following intratracheal instillation in rats appear to be similar for the sulphate,
phosphate and tetraoxide forms of Mn (half-time less than 0.5 days), the mechanisms of
clearance i.e. absorptive (dissolution) versus nonabsorptive (mechanical transport) for
each may be different (Vitarella et al., 2000a). These data underline differences in
absorption of different inorganic Mn species via different routes and in particular the
importance of inhalation exposure when considering neurological impacts of excessive
Mn.
Separate rodent studies show that absorption of Mn may occur also in the intranasal
airways and the uptake by olfactory neurons may serve as a pathway for Mn uptake
bypassing the blood-brain barrier. Recently, with neutron activation analysis, Vitarella
et al. (2000b) showed particular accumulation of Mn in the olfactory bulb in rats
following inhalation of Mn phosphate over 14 days. Brenneman et al (2000) also
confirmed transport of Mn to the brain via the olfactory pathway in a unilateral nasal
occlusion model in rats subject to a single 90 minute nose-only exposure to a Mn
chloride isotope. Other inhalation studies in the rat indicate that aqueous solubility is
predictive of Mn absorption in the lung and transport to the brain with exposure to more
soluble forms of Mn such as Mn sulphate resulting in higher brain Mn compared to
insoluble forms such as Mn tetraoxide (Dorman et al., 2001).
Absorption is also affected by diet. In humans, low dietary iron is associated with
increased Mn absorption, probably because iron and Mn share the same transport
mechanism in the gut. Similar results are observed in animals where Mn uptake is
increased by iron deficiency and decreased by pre-exposure to high dietary Mn levels.
In chicks, high dietary intakes of phosphorus and calcium also have been shown to
depress Mn uptake. Additionally, absorption is age-dependent. Human infants,
especially premature infants, retain a higher proportion of Mn than adults (Dorner et al.,
1989, cited in ATSDR, 2000).
Once absorbed, adult humans normally maintain stable tissue levels of Mn through
regulation of Mn excretion. Manganese is removed from the blood by the liver where it
is conjugated with bile and excreted into the small intestine. The majority is then
removed in faeces. Some of the Mn in the intestine is also reabsorbed via the hepatic
portal circulation. Excretion of Mn also occurs via urine, milk and sweat. In humans,
the whole-body clearance half-life of Mn is 37.5 days, while that for the head is 54 days
(Cotzias et al., 1968, cited in WHO 1981).
Methylcyclopentadienyl manganese tricarbonyl (MMT) 67
11.2 Human health effects
In humans, exposure to high levels of Mn is associated with adverse effects in
pulmonary, reproductive and nervous systems. However, the hallmark of excessive Mn
exposure is a progressive neurological syndrome featuring altered gait, tremor and
occasional psychiatric disturbances referred to as "manganism".
The neurological dysfunction of manganism appears to be related to both dose and
duration of Mn exposure. Initial signs may be vague and non-specific with complaints
of general weakness, muscle pain, irritability, apathy and headache. Loss of libido,
impotence, compulsive, aggressive or destructive behaviour may also occur.
Dysfunction of basal ganglia may occur next as indicated by altered gait, clumsy limb
movements, fine tremor, slow and halting speech and dull and expressionless facial
expressions. A characteristic staggering gait with erect spine may develop further
accompanied occasionally by psychological disturbances.
Isolated case reports describe manganism following occupational exposure to dusts or
fumes containing inorganic Mn in mining, alloy machining or battery manufacture
workers and also in individuals consuming water containing elevated Mn. However,
long-term match-controlled epidemiological studies are able to confirm subtle
neurological abnormalities in the absence of overt signs of manganism.
Neurobehavioural tests such as the WHO Neurobehavioural Core Test Battery, Swedish
Performance Evaluation System as well as supplementary manual dexterity and
questionnaire evaluations uncover subclinical alterations in neurological performance
and behavioural indicators associated with inhalation of Mn dusts or fumes. Subclinical
nervous system toxicity through to overt manganism have been observed after
inhalational exposure to total Mn dust levels ranging from 0.14-1.0 mg/m3 for the
former and from 2-22 mg/m3 for the latter with exposure durations of 1-35 years.
In response to difficulties in detecting the subtle neurobehavioural alterations of
manganism, magnetic resonance imaging (MRI) has been used in an attempt to detect
early signs of Mn exposure. In male workers exposed occupationally (mean exposure >
10 years) to Mn dioxide dust (personal monitoring mean total atmospheric Mn 387
礸/m3; blood Mn 14.8 礸/L; n = 11), Dietz et al. (2001) reported that despite the
inability to detect changes in electrophysiology, MRI scans revealed increases in the
ratio of globus pallidus to subcortical frontal white matter signal intensity (pallidal
index) in Mn exposed workers compared to matched control subjects (personal
monitoring mean total atmospheric Mn 10 礸/m3; blood Mn 11 礸/L; n = 11). These
changes are similar to those described by Kim et al. (1999) who reported increases in
pallidal index during MRI scans of asymptomatic Mn workers (blood Mn 14.2 礸/L; n
= 89) but not unexposed manual workers (blood Mn 11.7 礸/L; n = 16). Such changes
in imaging are noteworthy as they reflect recent exposure to Mn and deposition of Mn
in a brain area noted for association with Parkinsonian-like symptoms.
Few data are available regarding reversibility of neurological effects. The progression
of clinical symptoms of manganism in five surviving workers 9-10 years removed from
chronic 3-13 year exposure to Mn in a ferroalloy plant was documented by Huang et al.
(1998) (cited in ATSDR, 2000). Despite dramatic decreases in blood and tissue Mn
concentrations, neurologic examinations revealed a continuing deterioration of health
indicated by abnormalities in gait, rigidity and writing, suggesting progression and
permanence of neurological effects from frank Mn exposure.
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In a prospective study of a cohort of affected Mn dioxide exposed workers at a battery
plant, Roels et al. (1999) reported that a decrease in levels of Mn in total dust over 8
years was associated with normalisation of hand-forearm movement ability in a low
exposure subgroup (personal monitoring mean total atmospheric Mn approximately 400
礸/m3). However, medium (mean total Mn approximately 600 礸/m3) and high (mean
total Mn approximately 2000 礸/m3) exposure subgroups showed no or only partial
improvement in neurophysiological tests over this period.
In addition to neurological effects, acute and long-term inhalation of particulate Mn is
associated with inflammatory responses in lungs. Symptoms and signs include
reductions in lung function parameters, cough, bronchitis and pneumonia. Pneumonia is
reported from acute and long-term inhalation exposure mostly in occupational settings
but also in residential populations in proximity to Mn sources. A threshold level for
respiratory effects has not been established. It is possible that pulmonary irritation,
inflammation and increased susceptibility to infection may not be caused by Mn itself
but may be a secondary effect of the inhalation of matter in particulate form.
Reproductive effects are also associated with excessive Mn exposure. Impotence and
loss of libido are common symptoms in male workers showing clinical manganism
following chronic occupational exposure. Chronic occupational exposure of males has
been linked with impaired fertility as measured by decreases in numbers of children per
married couple. However, dose-response data are unavailable and so a threshold level
for reproductive effects in humans is not definable. Also, few data are available
regarding reproductive effects in women.
Several recent reports suggest a possible link between Mn exposure and the
development of the human prion disease known as Creutzfeldt-Jakob disease (CJD)
(Brown 2001). It has been established that prion protein when isolated from brain tissue
is bound to copper and that this interaction is necessary for the normal functioning of
the protein as an antioxidant (Brown et al. 2001). A central characteristic of prion
disease is the conversion of the normal prion protein to a corrupted form (Prusiner
1998). Experimental evidence suggests that the corrupted prion protein lacks
antioxidant activity, is resistant to proteinases, and aggregates to form fibrils (Prusiner
1982; Brown et al. 1997). It was subsequently demonstrated in vitro that the prion
protein can bind Mn and this interaction promotes the conversion to the corrupted form
(Brown et al 2000). Other evidence for a possible link between Mn and CJD is
provided from epidemiological studies. For example, Purdy (2000) reports that areas in
the UK that have unusually high incidence of prion disease also have high Mn and low
copper content in soil and plants. The reverse was noted for low prion disease areas. A
second example comes from Slovakia, where people living in areas that have a high
degree of industrial Mn contamination also have elevated body Mn levels. These same
areas are known to experience an unusually high incidence of sporadic CJD (Mitrova
1991; Purdy 2000). Overall, although a link is suggested, data are not sufficient to
define a causal relationship between Mn exposure and CJD.
The critical effect of chronic exposure to Mn is neurotoxicity although the pathogenic
mechanisms are not fully understood. Manganese-related neurobehavioural effects are
reported at lower doses in humans compared to animals suggesting that humans are
more sensitive to Mn. However, such differences may also be related to differences in
the sensitivity of test methods used to detect neurobehavioural effects in humans
compared to animals.
Methylcyclopentadienyl manganese tricarbonyl (MMT) 69
The most reliable and robust epidemiological study for Mn exposure is Roels et al.
(1992). In this study, neurofunctional endpoints were examined in 92 male workers
exposed to Mn dioxide dust at an alkaline battery factory. Manganese workers were
compared to a group of 104 age-matched control workers not exposed to neurotoxic
chemicals or lung irritants recruited from a polymer processing plant. The prevalence of
neuropsychological and respiratory symptoms and changes in lung ventilatory
parameters, neurofunctional performances (visual reaction time, eye-hand coordination,
hand steadiness, audioverbal short term memory) and several biological parameters
including luteinising hormone, follicle stimulating hormone and prolactin
concentrations in serum, blood counts and Mn concentrations in blood and urine were
examined. For each worker, current exposure and lifetime integrated exposure to
respirable and total airborne Mn dust were also determined. This allowed grouping of
exposed workers according to lifetime integrated exposures to respirable Mn dust
(<600, 600-1 200, >1 200 礸 Mn/m3 x year) and total Mn dust (<2 500, 2 500-6 000, >6
000 礸 Mn/m3 x year).
Manganese concentrations in blood and urine were significantly higher in the battery
workers compared to control workers. In individual workers, however, Mn levels in
blood or urine were not related to external exposure parameters. In comparison to
control workers, Mn workers showed significantly poorer performance for visual
reaction time, eye-hand coordination and hand steadiness. Underperformance was
related to lifetime integrated exposures to total and respirable Mn dust, being most
significant in the highest dose group.
From these data, a dose-response relationship was derived. A lower 95% confidence
limit was estimated around the level of Mn exposure expected to result in a 5%
response rate and this value (30 礸/m3) was considered a surrogate for a NOAEL for
neurological effects (WHO 1999; 2000).
Other dose-response estimates based on Roels et al. (1992) have derived a NOAEL of
32 礸/m3 and LOAEL of 50 礸/m3 (WHO 1999).
11.3 Effects in animals
Studies in animals identify the lungs and nervous system as target organs following
acute exposure to Mn. In rodents, lung inflammation is reported following acute
particulate inhalation exposures to 2.8-43 mg Mn/m3 as Mn dioxide or Mn tetraoxide. It
is notable again that inhalation of particulates in general are reported to cause
pulmonary inflammatory responses and thus lung inflammation seen with Mn may, at
least in part, be a generalised response to the physicochemical nature of the Mn load.
In different strains of rats, single oral exposures to Mn chloride by gavage have resulted
in LD50 values of 275-804 mg/kg bw/day. Similar single exposures to Mn sulphate and
Mn acetate have resulted in LD50 values of 782 and 1082 mg/kg bw/day respectively.
In non-lethal doses, decreased activity, alertness, muscle tone, touch response and
respiration have been recorded in mice dosed with 58 mg Mn chloride/kg bw by oral
gavage.
Little information is available regarding dermal toxicity, irritation and sensitisation
properties of inorganic Mn compounds, possibly due to low dermal absorption. A
single murine local lymph node assay study reported no cell proliferation with Mn salts
inferring little sensitisation potential.
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As in acute studies, neurological and pulmonary effects appear also to be a
consequence of repeated Mn exposure. In contrast to acute bolus gavage administration,
inorganic Mn appears to be more tolerated when administered over a longer term in
feeding studies. The apparent differences in survival for bolus gavage versus feeding
could be explained by species differences and/or the inability of clearance mechanisms
to adequately handle high acute loads versus similar loads spread over time (ATSDR
2000).
Mice showed increased susceptibility to infection when exposed to Mn dioxide via
inhalation for up to 4 days. Mild lung inflammation is reported in rhesus monkeys
exposed to atmospheric Mn dioxide for 10 months.
A spectrum of neurological effects has been recorded in animals following short-term
or chronic Mn exposure. Decreased motor activity or increased activity and aggression
have been observed in rodents in food or drinking water studies. Although no evidence
of neurological effects was observed in repeat dose studies in monkeys exposed to 20-
40 mg Mn chloride/m3, movement tremors with increased Mn in the globus pallidus
and substantia nigra have been reported in monkeys following IV administration of 5-
40 mg Mn/kg bw (as Mn chloride). In rodents, significant alterations in pup retrieval
and open field behaviour are also reported with short-term exposure to inorganic Mn
compounds.
In addition to activity and behavioural signs, repeat dose studies also report changes in
brain histochemistry, brain enzyme function and neurotransmitter levels in rats and
mice following Mn at oral doses ranging from 1 to 2270 mg Mn/kg bw over 14-364
days. Decreased levels of dopamine in the caudate and globus pallidus regions of the
brain are reported in rhesus monkeys exposed via inhalation for up to 2 years to 30 mg
Mn/m3 (as Mn dioxide). Neurochemical changes are also reported in neonate rats at Mn
levels similar to or slightly higher than dietary levels suggesting a particular
susceptibility of the young to Mn.
To further investigate the impact of Mn for susceptible subpopulations,
bioaccumulation and neurotoxicity of Mn have been investigated also in animal models
of chronic liver disease (Salehi et al., 2001). Male rats with portacaval anastomosis
were exposed via inhalation to 3050 礸/m3 Mn phosphate for 4 weeks. Mn levels in
blood, lung, cerebellum, frontal cortex and globus pallidus were significantly elevated
compared to unexposed portacaval shunted rats. Neuronal cell losses from the frontal
cortex, caudate putamen and globus pallidus was also significantly higher in Mn
exposed rats. These results show Mn bioaccumulation and neurotoxicity following
intranasal and respiratory tract (inhalation) exposure in animals with compromised Mn
clearance.
The exacerbating effects of Mn exposure on neurological dysfunction have also been
investigated in animal models of pre-parkinsonism (Witholt, Gwiazda and Smith 2000).
Female rats in which a pre-parkinsonism state was induced by intrastriatal injections of
6-hydroxydopamine received IP injections of 4.8 mg Mn/kg bw (as MnCl2) thrice
weekly for 5 weeks. In contrast to control pre-parkinsonism rats in which no
abnormalities were detected in neurobehavioural tests, rats also receiving Mn showed
significant impairment of neurobehaviour in 8 of 10 neurofunctional tests. These results
suggest that chronic Mn exposure may increase the risk of neurobehavioural
impairment in pre-parkinsonism subpopulations.
Methylcyclopentadienyl manganese tricarbonyl (MMT) 71
Animal studies also show effects of Mn exposure on reproduction and development.
Studies in rabbits, rats and mice report degenerative changes in the testes. In rabbits, a
single dose of 160 mg Mn/kg bw (as Mn dioxide) resulted in slow degeneration of
seminiferous tubules over 1-8 months with a loss of spermatogenesis leading to
infertility.
In female rats, slight decreases in pregnancy rates were observed with Mn exposure via
diet. In mice, exposure to 85 mg Mn/m3 via inhalation for 16 weeks prior to and 17
days after conception was reported to decrease pup weight and activity. In a similar
fashion to studies showing more efficient absorption of Mn following parental
compared to oral administration, other developmental studies suggest that parenteral
administration may cause greater toxicity when compared to administration via gavage.
In rats, IV injection of 1.1 mg Mn chloride/kg bw on gestation days 6-17 induced mild
skeletal malformations in foetuses. No effects were observed at 0.28 mg Mn/kg bw.
A recent fertility study was conducted by Elbetieha et al. (2001) in mice given Mn
chloride in drinking water at 1-8 g/L for 12 weeks. Males showed decreased fertility at
the highest dose but not at lower doses. Females showed no reductions in fertility at any
dose but numbers of implantations and viable foetuses were significantly reduced at the
highest dose. Females also showed significantly increased ovarian weights at 4 and 8
g/L and increased uterine weights at all doses. Although results are mixed, data indicate
that Mn has the capacity to induce reproductive and developmental effects in animals.
The carcinogenic potential of Mn has also been examined in rodent studies but only
limited oral exposure data are available and results are equivocal. Tumours of the lungs
(following IP injection), pancreatic, pituitary and thyroid gland follicular cell adenomas
are reported in separate studies in rats and mice but incidences are often not dose
responsive, only marginally increased compared to internal controls and often within
the bounds of historical controls. These data based on rodent studies do not provide
sufficient evidence for carcinogenic properties of Mn.
In reverse mutation assays in bacteria and fungi, at least some forms of inorganic Mn
are reported to have mutagenic potential. Mixed findings are also reported in in vitro
clastogenicity studies using mammalian and plant cell cultures. Similar inconsistencies
are also reported in in vivo mammalian studies. From these data, no firm conclusions
can be drawn regarding the genotoxic properties of Mn.
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12. Hazard Classification
This section discusses the classification of the health effects of MMT according to the
NOHSC Approved Criteria for Classifying Hazardous Substances (the Approved
Criteria) (NOHSC, 1999a) or, in the case of physicochemical hazards, the Australian
Code for the Transport of Dangerous Goods by Road
and Rail (ADG Code) (FORS, 1998). The Approved Criteria are cited in the NOHSC
National Model Regulations for the Control of Workplace Hazardous Substances
(NOHSC, 1994c) and provide the mandatory criteria for determining whether a
workplace chemical is hazardous or not.
Where adequate human data were unavailable, the classification for health hazards has
been based on experimental studies (animal and in vitro tests). In extrapolating results
from experimental studies to humans, consideration was given to relevant issues such
as quality of data, weight of evidence, metabolic and mode of action/mechanistic
profiles, inter- and intra-species variability and relevance of exposure levels.
Classification of MMT in accordance with the OECD Globally Harmonized System of
Classification and Labelling of Chemicals (GHS) (OECD 2002) can be found in
Appendix 4.
MMT (as Mn) is currently listed in the NOHSC List of Designated Hazardous
Substances (NOHSC, 1999b) with no classification. This is a result of several
chemicals being included on the Designated List because they had an exposure standard
already assigned by NOHSC.
12.1 Physicochemical hazards
MMT is a dark orange or yellow volatile liquid (vapour pressure 0.01 kPa at 20oC) with
a boiling point of 231.67oC and a flash point (closed cup) of 96oC. The ignition
temperature is 257癈.
With respect to the ADG Code (FORS 1998), MMT does not meet the criteria for
classification as a dangerous good on the basis of physicochemical hazards.
12.2 Health hazards
12.2.1 Acute toxicity
Animal studies with rats, rabbits and mice have shown MMT to induce damage to the
lungs by all routes, kidney, liver and spleen effects, tremors, convulsions, dyspnea and
weakness.
The LD50 for a single oral exposure to MMT for the rat ranges from 9 to 176 mg/kg
bw, with several values < 25 mg/kg bw. The LC50 for the rat ranges from 0.22 to 0.25
mg/L for a 1 hour exposure and > 0.002 to 0.076 mg/L for a 4 hour exposure.
The dermal LD50 values for undiluted MMT range from 140 to 795 mg/kg bw.
Methylcyclopentadienyl manganese tricarbonyl (MMT) 73
In humans, the acute effects of MMT by dermal or inhalation exposure are reported to
be burning of the skin, a metallic taste in the mouth, "thick tongue", giddiness,
headache, nausea, chest tightness, gastrointestinal upset, dyspnea, and paresthesia.
Symptoms appeared within 5-60 min post exposure and had abated by 2 days.
Classification:
Based on animal experiments, MMT meets the criteria of the ADG Code (FORS, 1998)
for classification as a toxic substance Class 6.1, Packing Group I.
MMT meets the Approved Criteria (NOHSC, 1999a) for acute lethal effects by the
inhalation route (R26 - Very Toxic by Inhalation), the oral route (R28 ?Very Toxic if
Swallowed) and dermal route (R24 ?Toxic in Contact with Skin).
12.2.2 Irritation and corrosive effects
Accidental exposure of human skin to MMT vapours for 30 minutes and 1.5 hours is
reported to result in a burning sensation of the skin. Symptoms appeared within 5-60
min post exposure and had abated by 2 days. Unfortunately, these reports lack detail
regarding the extent of dermal inflammation. In several adequately reported studies in
rabbits, MMT when applied for 24 hours was found to cause slight skin irritation.
Inadequate data exist to characterise the human ocular response to MMT. Rabbits
exhibited slight conjunctival redness and chemosis after direct exposure of the eye to
liquid MMT. The inflammatory response was resolved within 1-3 days.
In humans, accidental respiratory exposure to MMT vapours resulted in chest tightness.
Symptoms had abated by 2 days post exposure. There are no animal studies of
respiratory irritation from MMT.
Classification:
MMT does not meet the Approved Criteria (NOHSC, 1999a) for skin or eye irritation
and data are insufficient to classify for respiratory irritation.
12.2.3 Sensitising effects
There are no animal studies or human case reports of skin or respiratory sensitisation to
MMT.
12.2.4 Effects from repeated or prolonged exposure
There are no human case reports or studies detailing symptoms resulting from
prolonged exposure to MMT.
One limited study is available detailing the effects of repeated (30 week) inhalation
exposure to MMT in rats and mice. These animals showed weight loss and death at
0.014 mg/L MMT exposures and above. In mice at 0.014 mg/L, the percentage weight
loss reported was 26.2% and mortality occurred in 1/10 animals. At 0.017 mg/L, weight
loss increased to 35.9% and mortality occurred in 28 of 28 mice. Rats exposed to 0.017
mg/L showed 10.7% weight loss with mortality in 9 of 20 animals. Degenerative
changes resulting from MMT exposure were seen in the liver and kidney. The NOAEL
for rats and mice was 0.0062 mg/L.
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Reports of the effects of repeated dermal exposure to MMT in animals are limited to
one inadequate study where MMT in gasoline was applied to rats and rabbits at doses
up to approximately 32 mg MMT/kg bw/day for between 14 and 25 weeks respectively.
Repeated dermal contact with gasoline in the presence or absence of MMT resulted in
mild skin injury in rats and extensive injury in rabbits. At 4.8 and 32 mg/kg bw/day in
gasoline, vacuolar degeneration of the liver and kidney was observed in some rabbits.
The effects of repeated oral exposure to MMT are presented in several animal studies
examining neurological and developmental effects. In a neurological study, mice were
exposed to MMT in food (0.5 g Mn/kg food) for 12 months. MMT-treated mice
showed significant weight loss during exposure and neurotransmitter imbalances
following the 12 months exposure.
Three developmental studies document effects from oral exposure to MMT during days
6-15 of gestation. Slight weight loss in pregnant dams was observed with MMT at 2-9
mg/kg bw/day. In a second study, significantly reduced body weight gain was observed
at doses down to 5 mg/kg bw/day. At this lowest dose, rats showed epistaxis, irregular
or rapid breathing and urinary incontinence. Mortality was observed in 41 of 59 rats
receiving 20 mg/kg bw/day. A third study showed moderate weight reductions in rats
receiving 10 mg/kg bw/day and significant mortality at 20 mg/kg bw/day and above.
A repeat dose neurotoxicity study was conducted where female rats received up to 50
mg MMT/kg bw in propylene glycol via subcutaneous injections (24 injections over 48
days or 75 injections over 5 months). In animals receiving MMT over 5 months,
enzyme and neurotransmitter markers showed no changes compared to controls and
numbers of perikarya per unit area in the substantia nigra were also similar to controls.
Slight depressions of 3,4-dihydrophenylacetic acid in the striatum were observed in
animals receiving MMT over 48 days.
The neurotoxicity of MMT was assessed in male ddY mice after chronic oral
administration of MMT in food (0.5 g Mn/kg food) for 12 months. Between 4 and 6
animals were used per treatment with dosages equivalent to approximately 51.7 mg
Mn/kg bw/day (208.5 mg MMT/kg bw/day). MMT-treated mice showed significant
weight loss compared to controls during the 12-month treatment period. Spontaneous
motor activity was measured over a 30 minute period at intervals during the 12-month
exposure period. The level of spontaneous motor activity was similar for the control
and MMT-treated groups throughout the study, except on day 80, when the MMT-
treated group showed significantly more motor activity compared to controls.
Classification:
There are insufficient data for the classification of MMT against the Approved Criteria
(NOHSC, 1999a) with respect to severe effects after repeated/prolonged exposure via
oral or dermal routes. However, data are sufficient from the 30 week repeat dose
inhalation toxicity study for MMT to meet the Approved Criteria (NOHSC, 1999a) for
severe effects after repeated or prolonged exposure by the inhalation route (R48/23 ?br>
Toxic: Danger of Serious Damage to Health by Prolonged Exposure Through
Inhalation).
12.2.5 Reproductive effects
There have been no reports of adverse reproductive effects in humans attributed to
MMT in the literature. Also, no fertility studies have been conducted in animals.
Methylcyclopentadienyl manganese tricarbonyl (MMT) 75
Three developmental studies of MMT in rats have been conducted with two studies
establishing NOAELs of 9 and 10 mg/kg bw/day respectively for developmental
effects. Data were insufficient to establish a NOAEL in the third study. These studies
do not indicate that exposure levels below those associated with maternal toxicity
significantly affect embryonic or foetal development.
Classification:
There are insufficient data for the classification of MMT against the Approved Criteria
(NOHSC, 1999a) with respect to fertility effects (R60). MMT does not meet the
Approved Criteria (NOHSC, 1999a) for developmental effects (R61).
12.2.6 Genotoxicity
The results of Ames testing (with or without metabolic activation), using several strains
of S. typhimurium were negative for MMT. A mutation assay with S. cerevisiae (with
or without metabolic activation) was also negative.
One unpublished study investigated the ability of MMT to promote chromosomal
aberrations in a mammalian cell line (CHO). MMT was found to induce chromosomal
aberrations when cultured in the presence of a metabolic activator in vitro.
In another unpublished study investigating the ability of MMT to induce chromosomal
effects in vivo, MMT was found not to increase the number of micronucleated
polychromatic erythrocytes in mice.
MMT was found not to cause dominant lethal effects when male mice were dosed by
gastric intubation at up to 160 mg/kg bw/day for five consecutive days.
Classification:
MMT does not meet the Approved Criteria (NOHSC, 1999a) for mutagenic effects
(R40, R46).
12.2.7 Carcinogenicity
One limited study is available examining the ability of MMT to affect lung tumour
development in mice. Intraperitoneal injections of MMT (80 mg/kg bw) in oil once a
week for six weeks did not enhance lung tumour formation in NaCl or urethan pre-
treated mice.
Classification:
There are insufficient data for the classification of MMT against the Approved Criteria
(NOHSC, 1999a) with respect to carcinogenic effects (R40, R45, R49).
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13. Effects on Organisms in the
Environment
This section provides information on the effects of MMT and Mn, the predominant
combustion by-product, on animals and plants. Based on MMT use patterns, the review
of effects has included the potential effects to organisms typically inhabiting terrestrial
and aquatic environments.
The following information on MMT has been obtained from Kem-Tech Laboratories
(1977) and Analytical Bio-chemistry Laboratories, Inc. (1990). Information on Mn, a
component of MMT, has been obtained from various sources but principally the United
States Environmental Protection Agency (USEPA) Ecotox Database (USEPA, May
2000) and the Australian and New Zealand Water Quality Guidelines (ANZECC and
ARMCANZ, 2000). As these reference sources on Mn have been peer-reviewed, all of
the publications referenced from these sources have not been peer reviewed for this
present report (see citation for specific reference sources). Table 14 provides a
summary of toxicity test data for aquatic organisms.
Table 14. Summary of aquatic toxicity data for MMT and Manganese
Taxa Habitat Compound NOEC (mg/L) LC(EC)50 (mg/L)
---
Plants/Algae Freshwater MMT ---
4.5 (a) 4.98 (b)
Mn
Marine MMT --- ---
Mn 25.7 (c)
---
0.29 (d) 0.83 (e)
Invertebrates Freshwater MMT
Mn 3.9 (f) 4.7 (g)
Marine MMT --- ---
Mn 1-10 (h)*
---
<0.14 (i) 0.20 (j)
Fish Freshwater MMT
0.96 (k) (as
Mn 33.8 (m)
LC10)
Marine MMT --- ---
Mn --- ---
Amphibians Freshwater MMT --- ---
14.3 (n)
Mn ---
Sources:
a. Den Dooren and de Jong, 1965 as cited h. MacDonald et al., 1988.
by USEPA, 2000 i & j. Kem-Tech Laboratories, 1977.
b. Fargasova et al., 1999. k. Birge et al., 1981 as cited by
c. Rosko and Rachlin, 1975 as cited by USEPA, 2000.
USEPA 2000. m. Kimball, 1978.
d & e. Analytical Bio-chemistry Laboratories, n. Rao et al., 1987, as cited by
Inc., 1990. USEPA, 2000.
* Range derived from MacDonald et
f. Kimball, 1978 as cited by USEPA,
al., 1988.
2000
---No data available.
g. Baird et al., 1991.
Methylcyclopentadienyl manganese tricarbonyl (MMT) 77
13.2 Terrestrial animals
13.2.1 MMT
Kinetics/metabolism and toxicity of MMT to mammals (e.g. rats, mice, monkeys,
rabbits) have been presented in Sections 9 and 10, respectively. No information was
available on the potential effects of excessive MMT exposure to birds or other
terrestrial organisms.
13.2.2 Manganese
Mammalian toxicity data for inorganic Mn compounds resulting from MMT
combustion have been presented in Section 11. No information was available on the
potential effects of excessive Mn exposure to birds or other terrestrial organisms.
13.3 Terrestrial plants
13.3.1 MMT
No information was available on the toxicity of MMT to terrestrial plants.
13.3.2 Manganese
Manganese is an essential trace element for micro-organisms, plants and animals
(CCREM, 1987, as cited by ANZECC and ARMCANZ, 2000). It is involved in
nitrogen assimilation, as a catalyst in plant metabolism and functions with iron in the
synthesis of chlorophyll (Labanauskas, 1966, as cited by Efroymson et al., 1997).
Toxicity symptoms include marginal chlorosis and necrosis of leaves and root
browning. Excess Mn interferes with enzymes, decreases respiration and is involved in
the destruction of auxin (Foy et al., 1995, as cited in Efroymson et al., 1997).
Plant uptake of soil Mn occurs mainly via the roots of plants. However, intake through
leaves may also contribute a fraction of the total uptake, and leaf uptake is slower
(May, 1998). Fertilizer application of Mn to crops and other plants is undertaken to
correct Mn deficiency by either soil or foliage application.
Most Mn in soils is precipitated as Mn oxide or hydroxide; however, the Mn2+ ion is the
form available to plants. Soil Mn recommendations are based on the soil pH and crop
being grown.
Excessive soil Mn may be problematic in acid soils (approximately pH <4.8; Rosen and
Eliason, 2002). A toxic Mn situation may also develop in plants if excessive soil and/or
foliar applications are used. Foliar-applied Mn fertilizer in excess of recommended
amounts for Mn deficiency adjustment, or in small volumes of water, may burn leaves
of plants (e.g. wheat, oats and sugar beets; Ohio State University, 1996).
In the early stages of plant growth, Mn toxicity symptoms may be similar to deficiency
symptoms (e.g. interveinal chlorosis). Spotting, scorching on leaf margins and cupping
of leaves are also typical toxicity symptoms. In potatoes, the symptoms are chlorosis
and black specks on the stems and undersides of the leaves, followed by death of the
lower leaves. Crops, including alfalfa, cabbage, cauliflower, clover, dry edible beans,
potatoes, small grains, sugar beets and tomatoes, are sensitive to excess Mn.
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Plant tissue analysis is used to diagnose Mn status in plants. Values below 20 mg/kg are
usually considered deficient. Readings of 30 to 200 mg/kg are normal, and those over
300 mg/kg may lead to adverse effects.
Liming soils to the desired pH range for the crop will usually prevent soil Mn toxicity.
Soil Mn may be classified by concentrations as follows: Very High >400 mg/kg, High
201 to 400 mg/kg, Medium 51 to 200, Low 25 to 50 mg/kg and Very Low <25 mg/kg
(Stanley and Baker, 2002).
Efroymson et al. (1997) has established soil (bulk) and soil solution toxicity
benchmarks for Mn of 500 mg/kg in soil and 4 mg/L in soil solution. Wallace et al.
(1977) evaluated the effects of Mn, added as MnSO4 to a loam soil, on leaf and stem
weights of bush beans grown from seed for 17 days. Stem weight was reduced 29% by
500 mg Mn/kg. This was the lowest concentration tested. As the 500 mg/kg benchmark
for Mn is based on this one study, confidence in the benchmark is low; however,
confidence in the soil solution benchmark is higher as more data are available
(Efroymson et al., 1997). As indicated above, soil Mn toxicity is a function of soil pH
as well as Mn concentration.
No published phytotoxicity data were available on the acceptable concentration of Mn
in air for terrestrial plants. Recommended rates for foliar Mn fertilizers vary but range
between approximately 0.008 and 2 kg Mn/ha, and frequent applications may be
required (Vitosh, 1990; Barmac, 2002). Recommended foliar concentrations also vary
but approximate 0.7 to 1.1 mg Mn/L (Barmac, 2002).
The information available indicates that Mn is an essential nutrient for plants and of
low toxicity but exposure to high to very high soil Mn concentrations, combined with
low pH soil conditions, or excessive foliar Mn may lead to adverse effects in plants.
Adverse effects arise mainly due to excessive soil Mn bioavailability and toxicity from
foliar application is unlikely.
13.4 Aquatic plants
13.4.1 MMT
No information was available on the toxicity of MMT to aquatic plants.
13.4.2 Manganese
Manganese is widely distributed in the earth's crust, most commonly as MnO2. It is
present in natural waters in suspended form (similar to iron) although soluble forms
may persist at low pH or low dissolved oxygen (ANZECC and ARMCANZ, 2000).
The information presented below indicate that Mn is slightly to moderately toxic to
freshwater and marine aquatic plants with acute LC(EC)50 values in the range of 4.98
mg/L or greater (Mensink et al., 1995).
Freshwater aquatic toxicity data for Mn were available for 7 aquatic plant species
including 2 macrophytes and 5 species of algae. The data are summarised in Table 15.
Methylcyclopentadienyl manganese tricarbonyl (MMT) 79
Table 15. Summary of aquatic phytotoxicity data for manganese
Species Endpoint Result Reference
(mg/L)
Duckweed Lemna 96-hour EC50 (growth) 31 Wang ,1986, as cited by
minor USEPA, 2000
Rice Oryza sativa 144-day IC50 (growth) 100 Wang ,1994, as cited by
USEPA, 2000
Green algae 12-day EC50 (growth) 4.98 Fargasova et al., 1999
Scenedesmus
quadricauda 12-day EC50 values 1.91 - 2.28 Fargasova et al., 1999
(chlorophyll content)
Algae Chlorella NOEC (population 4.5 Den Dooren & de Jong,
vulgaris growth) 1965, as cited by
USEPA, 2000
LOEC (population 11 Den Dooren & de Jong,
growth) 1965, as cited by
USEPA, 2000
Algae Chlorella 84-hour 100 Wong et al., 1980, as cited
pyrenoidosa, C. by USEPA, 2000
salina & S. 144-hour LT50 50 Wong et al., 1980, as cited
quadricauda by USEPA, 2000
Two studies have investigated the effects of Mn to marine diatoms (Fisher and Jones,
1981, as cited by USEPA, 2000; Rosko and Rachlin, 1975, as cited by USEPA, 2000).
The 96-hour EC50 (growth) values for diatoms (Asterionella japonica and Nitzschia
closterium) range from 25.7 to 53.8 mg/L.
13.5 Aquatic invertebrates
13.5.1 MMT
The acute (48 hour) toxicity of MMT (95% purity) was studied in cultured neonates
(<24 hours old) of the freshwater crustacean Daphnia magna (waterfleas) under static
test conditions (Analytical Bio-chemistry Laboratories, Inc., 1990). The study was
undertaken with measured MMT concentrations (means) of 0, 0.29, 0.65, 1.0, 2.0, and
3.5 mg/L. Measured concentrations were less than estimated nominal concentrations,
presumably due to photodegradation of MMT. Test dilution water had hardness 172
mg/L (as CaCO3), alkalinity 192 mg/L (as CaCO3), pH 7.9, and conductivity 325
礛hos/cm. The 48-hour EC50 was 0.83 mg/L (95% C.I. 0.70 to 0.99 mg/L). The 4-
hour and 24-hour EC50 were 0.87 and 0.94 mg/L, respectively. The 48-hour NOEL,
based on the absence of immobility and abnormal effects, was 0.29 mg/L. Abnormal
effects including immobility and surfacing were observed with the mean measured
MMT concentrations of 0.65 mg/L and greater under test concentrations.
Acknowledging data limitations, these results for Daphnia magna suggest that MMT
may be considered highly toxic to aquatic invertebrates, with acute LC(EC)50 values in
the range of <1 mg/L (Mensink et al., 1995).
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13.5.2 Manganese
The information presented below indicates that Mn is slightly to moderately toxic to
freshwater and marine invertebrates with acute and chronic LC(EC)50 values in the
range of 1 to 10 mg/L (Mensink et al., 1995).
Manganese is a neurotoxin and can block the release of neurotransmitters such as
acetylcholine, while inhibiting acetylcholine esterase activity (Skukla and Singhal,
1984, as cited by MacDonald et al., 1988).
Acute and chronic toxicity data for Mn are available for several species of freshwater
invertebrates with acute and chronic LC50 values ranging from 12.6 and 9 mg/L,
respectively. Sublethal effects including intoxication and aberrant reproduction have
been recorded above 4.7 mg/L. The data are summarised in Table 16.
Table 16. Summary of freshwater invertebrate toxicity data for manganese
Species Endpoint Result Reference
(mg/L)
Crayfish 4-day LC50 28 - 51 Boutet and Chaisemartin, 1973, as cited
Austropotamobius by USEPA, 2000
pallipes & Boutet and Chaisemartin, 1973, as cited
30-day LC50 17 - 34
Orconectes by USEPA
limosus
24-hour LC50 38.7 Couillard et al., 1989, as cited by
Rotifer
USEPA, 2000.
Brachionus
calyciflorus
12.6
Waterfleas Acute LC50 Sorvari and Sillanpaa, 1996, as cited by
Daphnia magna USEPA, 2000; Kimball, 1978, as cited
by USEPA, 2000; Cabejszek and Stasiak,
1960, as cited by USEPA, 2000
21-day LC50 9 Kimball , 1978, as cited by USEPA, 2000
4.7
EC50 (intoxication) Baird et al., 1991; Anderson, 1948 as
cited by USEPA, 2000; Biesinger and
Christensen, 1972 as cited by USEPA,
2000; Khangarot and Ray, 1989 as cited
by USEPA, 2000; Rossini and Ronco,
1996 as cited by USEPA, 2000
28
48-hour NOEC Bowmer et al., 1998 as cited by
(intoxication) ANZECC and ARMCANZ, 2000
48-hour EC50 Bowmer et al., 1998, as cited by
40
(intoxication) ANZECC and ARMCANZ, 2000
21-day EC50 5.7 Biesinger and Christensen, 1972 as cited
(intoxication) by USEPA, 2000
Methylcyclopentadienyl manganese tricarbonyl (MMT) 81
Table 16. Summary of freshwater invertebrate toxicity data for manganese
(cont.)
Species Endpoint Result Reference
(mg/L)
21-day EC50 5.2 Biesinger and Christensen, 1972 as cited by
(reproduction) USEPA, 2000
28-day NOEC 1.1 Kimball, 1978 as cited by USEPA, 2000
7-day NOEC 3.9 Kimball , 1978 as cited by USEPA, 2000
a
1.1 Kimball, 1978 as cited by USEPA, 2000
28-day MATC
5.5 Kimball, 1978 as cited by USEPA, 2000
7-day MATC
301 & Khangarot, 1991 as cited by USEPA, 2000
Tubificid worm 24- and 96-hour
270
Tubifex tubifex EC50 Khangarot, 1991 as cited by USEPA, 2000
(intoxication)
48-hour EC50 771 Martin and Holdich, 1986 as cited by USEPA,
Sowbugs
(intoxication) 2000
Asellus
aquaticus: 96-hour EC50 333 Martin and Holdich, 1986 as cited by USEPA,
Crustacea (intoxication) 2000
1389 Martin and Holdich, 1986 as cited by USEPA,
48-hour EC50
Aamphipods
2000
(intoxication)
Cragonyx
pseudogracilis 694 Martin and Holdich, 1986 as cited by USEPA,
96-hour EC50
2000
(intoxication)
24-hour LC50 92.8 Nalecz-Jawecki and Sawicki, 1998 as cited by
Protozoa
USEPA, 2000
Spirostomum
ambiguum 48-hour LC50 109 Nalecz-Jawecki and Sawicki, 1998 as cited by
USEPA, 2000
148 Nalecz-Jawecki and Sawicki, 1998 as cited by
24-hour EC50
USEPA, 2000
(development)
146 Nalecz-Jawecki and Sawicki, 1998 as cited by
48-hour EC50
USEPA, 2000
(development)
3-hour IC50 152
Ciliates Sauvant et al., 1995 as cited by USEPA, 2000
Tetrahymena 6-hour IC50 117 Sauvant et al., 1995 as cited by USEPA, 2000
pyriformis 9-hour IC50 106 Sauvant et al., 1995 as cited by USEPA, 2000
Maximum acceptable threshold concentration (MATC) is a hypothetical threshold concentration that
a.
is the geometric mean between the NOEC and LOEC concentration.
Manganese toxicity data are available for several species of marine invertebrates with
acute toxicity (mortality) in the range of between 16 to 75 mg/L and chronic EC50
values in the range of 1 to 10 mg/L (refer Table 17).
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Table 17. Summary of saltwater/marine invertebrate toxicity data for Manganese
Species Endpoint Result Reference
(mg/L)
American oyster 48-hour LC50 16 Calabrese et al., 1973 as
Crassostrea virginica cited by USEPA, 2000
Blue mussel Mytilus 48-hour EC50 30 Morgan et al., 1986 as cited
edulis by USEPA, 2000
Harpacticoid copepod 96-hour LC50 70 Bengtsson, 1978 as cited
Nitocra spinipes by ANZECC and
ARMCANZ, 2000
Brine shrimps Artemia 24-hour LC50 75 Gajbhiye and Hirota, 1990
spp. as cited by USEPA, 2000
Gajbhiye and Hirota , 1990
48-hour LC50 51.8
as cited by USEPA, 2000
Starfish Asterias rubens 72-hour LT50 50 Hansen and Bjerregaard,
1995 as cited by USEPA,
2000
10 - 100 MacDonald et al., 1988
Yellow Crabs Cancer 96-hour LD50
anthonyi (embryo mortality)
96-hour EC50 1 to 10 MacDonald et al., 1988
(hatching success)*
0.02 Watling (1983)
Oyster Crassostrea gigas NOEC (larval
settlement &
behaviour)
* ANZECC and ARMCANZ (2000) noted the apparent spurious data generated in this study for lower
tested concentrations of manganese.
MacDonald et al. (1988) noted that embryos of the crab species Cancer anthonyi live
on the outside of the adult crab and may receive a higher exposure than many other
aquatic organisms, explaining the higher sensitivity compared to other aquatic
organisms. MacDonald et al. (1988) suggest that adverse effects of metals such as Mn
may not be expressed within the typical time frame of standard toxicity tests (e.g. 96
hours), and that effects of Mn may not be fully expressed until at least 120 hours.
However as they indicated, the increased rate of effects they noted at 120 hours in the
toxicity test coincided with a peak in metamorphosis and hatching of viable embryos,
which may be a more sensitive life stage. Other confounding factors in the tests, such as
disease, cannot be excluded.
Eggs of the marine crab Carcius maenas can accumulate Mn during ovogenesis
(Martin, 1976a, as cited in MacDonald et al., 1988). Further, eggs of the marine crab
Cancer irroratus can accumulate Mn following exclusion, due to their selective
adsorption to the chitinous vitelline membrane (Martin, 1976b, as cited in MacDonald
et al., 1988). Bioconcentration of Mn by these crab species, may explain the high
sensitivity of these species to Mn relative to other marine organisms (e.g. Rao and
Saxema, 1981, as cited in MacDonald et al., 1988; Morgan et al., 1986, as cited in
USEPA, 2000).
Watling (1983) investigated the effects of Mn on settlement of the oyster Crassostrea
gigas, finding no effects on larval settlement or larval behaviour (as evidenced by foot
Methylcyclopentadienyl manganese tricarbonyl (MMT) 83
extension and crawling movement) when exposed to 0.02 mg/L. This was the highest
concentration tested. The author suggested that minor effects in growth of 51-day old
young (spats) may have been evident following 14-days exposure to Mn at the lowest
concentration tested (i.e. 0.01 mg/L). However, further testing would be required to
verify this hypothesis, and spat growth recovered following removal to clean seawater
for 14 days.
13.6 Fish
13.6.1 MMT
The acute (96-hour) toxicity of MMT was studied in two species of freshwater fish -
Bluegill sunfish (Lepomis macrochirus) and Fathead Minnow (Pimphales promelas)
under static test conditions (Kem-Tech Laboratories, 1977). Bioassays were conducted
with three applied concentrations of MMT with 10 fish in 12 litres (in 20 litre glass
cylinders). Test dilution water had a hardness of approximately 125 ppm (as CaCO3),
pH 7.0 and dissolved oxygen (saturated). Light was limited as much as practical during
the tests with MMT. The fish were conditioned to semi-dark conditions at 20癈. MMT
was added to the medium with acetone as solvent.
The Kem-Tech Laboratories (1977) study was undertaken in duplicate with measured
MMT concentrations (means) of <0.04 (control), 0.14, 0.25 to 0.36, and 0.45 to 0.47
mg/L. Measured concentrations were less than estimated nominal concentrations,
presumably due to both spontaneous degradation of MMT and MMT degradation
associated with contact with fish. MMT concentrations in each test solution declined
significantly throughout the test duration.
Median Threshold Limit (TLm or TL50) is the concentration of a chemical estimated to
kill 50% of exposed organisms in a given time period. It is often used interchangeably
with aquatic LC50 (USEPA, 1977). TLm concentrations (measured, mg/L) over 12, 24,
48, 72 and 96 hours for L. macrochirus and P. promelas are summarised in Table 18.
Table 18. Summary of freshwater fish toxicity data (TLm mg/L) for MMT
Fish Species 12 Hours 24 Hours 48 Hours 72 Hours 96 Hours
P. promelas 0.23 - 0.36 0.23 - 0.36 0.21 - 0.34 0.21 - 0.34 0.21 - 0.34
L. macrochirus 0.20 0.20 0.20 0.20 0.20
As indicated above, most lethality occurred within the first 12 hours. Mortality was rare
in the initial hour in tests under 3 ppm (measured). However, stress was evident in the
first few minutes (Kem-Tech Laboratories, 1977). The constancy of effects through
time probably reflects the rapid degradation of MMT from the test solutions.
Monitoring of MMT in test solution indicated 80 to 88% reduction in MMT within a
96-hour period. TLm results beyond 12 hours are probably not reliable. The lowest 12-
hour TLm derived for MMT was 0.20 mg/L. Sensitivity to MMT was similar between
the species, with mortality evident in the concentration of 0.18 to 0.34 mg/L or greater.
Survival was evident below an exposure concentration of 0.18 mg/L. However, stress
(irritation) was evident in fish at the lowest test concentration (0.14 mg/L). The
threshold for stress was not determined. Recovery from stress was evident following
cessation of exposure.
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The mode of toxicity in both fish species tested was similar with symptoms including
fitful activity, gradual loss of equilibrium (horizontally usually first, then vertically),
excess mucous production except in the lowest test concentrations, and finally gulping
at the surface with fitful swimming.
Acknowledging data limitations, these results suggest that MMT may be considered
highly toxic to fish, with acute LC(EC)50 values in the range of <1 mg/L (Mensink et
al., 1995).
13.6.2 Manganese
The data presented below indicate that Mn is slightly to moderately toxic to freshwater
fish with acute and chronic LC(EC)50 values in the range of 10 to 100 and 1 to 10
mg/L, respectively (Mensink et al., 1995). Several studies have investigated the effects
of Mn on freshwater fish. ANZECC and ARMCANZ (2000) reported acute (48 to 96-
hour) LC50 values of 33.8 to 4540 mg/L. Several data are available on the effects of
chronic exposure of freshwater fish to Mn, and chronic NOEC values in the range of
1.27 to 9.99 mg/L (growth and mortality). The toxicity data have been summarised in
Table 19.
Table 19. Summary of freshwater fish toxicity data for manganese
Species Endpoint Result (mg/L) Reference
Fathead minnows Pimphales 96-hour LC50 33.8 Kimball (1978), as cited
promelas by USEPA, 2000
Longfin dace Agosia 96-hour LC50 130 Lewis (1978), as cited
chrysogaster by USEPA, 2000
Silverside Basilichthys 96-hour LC50 >50 Trucco et al. (1991), as
australis cited by USEPA, 2000
Giant gourami Colisa 24-hour LC50 478 Nath and Kumar (1987),
fasciata as cited by USEPA,
48-hour LC50 345
2000
72-hour LC50 324
Nath and Kumar (1987),
96-hour LC50 295
as cited by USEPA,
2000
Nath and Kumar (1987),
as cited by USEPA,
2000
Nath and Kumar (1987),
as cited by USEPA,
2000
96-hour LC50 1040 Agrawal and Srivastava
(1980), as cited in
USEPA, 2000
Methylcyclopentadienyl manganese tricarbonyl (MMT) 85
Table 19. Summary of freshwater fish toxicity data for manganese (cont.)
Species Endpoint Result (mg/L) Reference
Medaka Oryzias latipes 24-hour LC50 >1000 Tsuji et al. (1986), as
cited by USEPA, 2000
Tsuji et al., 1986, as
48-hour LC50 >1000 cited by USEPA, 2000
Rainbow trout 4-hour LC01 0.39 Birge et al., 1981 as
Oncorhynchus mykiss cited by USEPA, 2000
Birge et al., 1981 as
cited by USEPA, 2000
4-hour LC10 0.96
28-day LC50 2.91 Birge et al., 1980 as
cited by USEPA, 2000
100-day MATC a 0.77 -1.53 b Goettl and Davies, 1978
as cited by USEPA,
2000
Goldfish Carssius auratus 7-day LC50 8.22 Birge, 1978 as cited by
USEPA, 2000
Fathead Minnow Pimphales 8-day LC50 34.6 Kimball, 1978 as cited
promelas by USEPA, 2000
19.7 Kimball, 1978 as cited
28-day LOEC
(mortality) by USEPA, 2000
28-day MATC 14.0 Kimball, 1978 as cited
(mortality) by USEPA, 2000
28-day NOEC 9.99 Kimball, 1978 as cited
(mortality) by USEPA, 2000
2.48 Kimball , 1978 as cited
LOEC (growth)
by USEPA, 2000
MATC (growth) a 1.77 Kimball, 1978 as cited
by USEPA, 2000
1.27 Kimball, 1978 as cited
NOEC (growth)
by USEPA, 2000
4.67 - 8.68 c
Brown trout Salmo trutta 62-day IC25 Stubblefield et al., 1997
as cited by USEPA,
2000
62-day NOEC 4.41 Stubblefield et al., 1997
(mortality as cited by USEPA,
2000
62-day NOEC 4.55 Stubblefield et al.,
1997 as cited by
(growth)
USEPA, 2000
a - Maximum acceptable threshold concentration (MATC) is a hypothetical threshold concentration that is
the geometric mean between the NOEC and LOEC concentration. b - Range not refined. c. Water
hardness dependent (refer below).
Stubblefield et al. (1997), as cited by USEPA (2000), determined that water hardness
significantly affects Mn chronic toxicity, with toxicity decreasing with increasing
hardness. Using early life stage brown trout (Salmo trutta), Stubblefield et al. (1997)
derived 62-day 25th percentile inhibitory concentration (IC25) values, based on the
combined endpoints (i.e., survival and body weight), were 4.67, 5.59, and 8.68 mg/L
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(based on measured Mn concentrations) at hardness levels of approximately 30, 150,
and 450 mg/L as CaCO3, respectively. NOEC values (62-day) for mortality and growth
were 4.41 mg/L and 4.55 mg/L, respectively.
No toxicity data were available on the effects of Mn on saltwater fish species.
13.7 Amphibians
13.7.1 MMT
No toxicity data were available on the effects of MMT on amphibians.
13.7.2 Manganese
Acute toxicity data were available for one frog species. Rao et al. (1987), as cited by
USEPA, 2000, derived 24-, 48-, 72- and 96-hour LC50 values for Mn for tadpoles of
ornate narrow-mouthed Frog Microhyla ornata in the range between 17.5 to 14.3 mg/L.
13.8 Summary of environmental effects
13.8.1 MMT
Following the guidelines from Mensink et al. (1995) and laboratory-derived aquatic
toxicity data, MMT may generally be regarded as highly toxic to aquatic invertebrates
and fish, with acute LC(EC)50 values in the range of <1 mg/L. Effects of MMT in
aquatic animals may include mortality, immobility, fitful activity, gradual loss of
equilibrium (horizontally usually first, than vertically), excess mucous production
except in the lowest test concentrations, and finally gulping at the surface with fitful
swimming.
A predicted no effect concentration (PNEC) for MMT to freshwater organisms of 0.014
mg/L has been derived by applying a standard assessment factor of 10 to the lowest
available NOEC data of 0.14 mg/L for freshwater fish (Kem-Tech Laboratories, 1977).
There is currently no environmental hazard classification system in Australia. In
accordance with the OECD Globally Harmonized System of Classification and
Labelling of Chemicals (OECD 2002), MMT would be classified Chronic 1 Very Toxic
to Aquatic Life with Long-lasting Effects.
13.8.2 Manganese
Aquatic toxicity of MMT is high relative to Mn, which may be regarded as slightly to
moderately toxic to aquatic organisms with chronic exposure effects in the 1 to 10
mg/L concentration range (Mensink et al., 1995).
Manganese is a naturally occurring element and essential for nutrition in plants and
animals. Typical concentrations of Mn in marine and freshwaters approximate 0.003 to
0.38 and 1.5 礸/L, respectively (ANZECC and ARMCANZ, 2000).
ANZECC and ARMCANZ (2000) provide a quality guideline (trigger level) for Mn for
the protection of freshwater ecosystems of 1.7 mg/L. They calculated this moderate
reliability trigger value for Mn using a statistical distribution method with 95%
Methylcyclopentadienyl manganese tricarbonyl (MMT) 87
protection and an acute to chronic ratio (ACR) of 9.1. This trigger level is considered to
be a suitable predicted no effect concentration (PNECFreshwater) for this assessment.
Insufficient toxicity data were available for marine organisms for ANZECC and
ARMCANZ (2000) to derive a marine trigger value. They derived a marine interim
indicative working level (IIWL) for Mn of 0.8 mg/L. This IIWL was derived by
dividing the lowest available acute LC(EC)50 by a standard assessment factor of 20
(Bonnell and Atkinson, 1999, as cited by ANZECC and ARMCANZ, 2000). The
lowest acute 48-hour LC50 was 16 mg/L for the American oyster C. virginica
(Calabrese et al., 1973, as cited by USEPA, 2000). The value of 0.8 mg/L is considered
a suitable PNECMarine for this assessment.
The PNECMarine and PNECFreshwater values are not widely dissimilar in magnitude;
however, there is greater uncertainty in the PNECMarine than the PNECFreshwater due to the
lesser amount of marine aquatic toxicity data available (ANZECC and ARMCANZ,
2000).
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14. Risk Characterisation
In this section, the results of the health hazard and occupational exposure assessments
are integrated to characterise the risk of adverse effects to workers potentially exposed
to MMT.
14.1 Environmental risk
This section provides a characterisation of risks to the environment from use of fuels
containing MMT as an AVSR.
A hazard quotient (HQ) approach has been used to predict the hazard to terrestrial and
aquatic organisms. To predict a low environmental risk, the ratio of PEC to PNEC
needs to be 1 or less (i.e. HQ 1).
14.1.1 Terrestrial risk
Most of the MMT used each year will be destroyed during combustion within internal
combustion engine cylinders. MMT is unstable to photochemical degradation in the
atmosphere with an estimated half-life of 8 to 18 seconds (Ter Haar et al. 1975). In
water bodies, MMT is likely to degrade in sunlight with a half-life of approximately 1
minute. However, in deeper waters, photodegradation may be reduced and hydrolysis
slow.
Following combustion, the Mn component in MMT is converted to a mixture of Mn
compounds (Mn phosphates, oxides and sulphates), and most will apparently remain in
the exhaust train. However, approximately 20% of these Mn compounds may be
emitted with exhaust gases associated with very fine particles (< 2.5 祄). These
particles have a low quiescent air sedimentation velocity, and may remain suspended in
air for a prolonged period. Ultimately, settlement to the earth surface (land and water)
will occur, with Mn becoming associated with soils, waters and aquatic sediments.
A predicted no effect concentration (PNECmammals) of 6.2 mg/m3 (inhalation) has been
derived for mammals exposed to MMT (Section 10.4). Concentrations of MMT in air at
a petrol station using MMT in Canada approximated 12 ng/m3 and concentrations were
lower in other areas sampled (see Table 5). Given this air MMT concentration at a high
use area, and that MMT degrades rapidly when exposed to sunlight, terrestrial wildlife
are unlikely to be exposed to MMT in air at levels of concern.
Conservative estimation of potential Mn levels in air indicates an Mn concentration
(PEC) of up to 49 ng/m3 (Table 6) for the Present Use scenario. This PEC is several
orders of magnitude lower than the conservatively estimated PNECmammals of 11.6礸/m3
for Mn in air.
Although no published phytotoxicity data were available on the acceptable
concentration of Mn in air for terrestrial plants, no records of adverse effects on plants
have been noted in the literature in MMT use areas. The information available indicates
that Mn is an essential nutrient for plants and of low toxicity but exposure to high to
very high soil Mn concentrations combined with low pH soil conditions, or excessive
Methylcyclopentadienyl manganese tricarbonyl (MMT) 89
foliar Mn may lead to adverse effects in plants. However, plants have a propensity to
tolerate foliar exposure to Mn and recommended foliar concentrations of Mn typically
approximate 1 mg/L, which is several orders of magnitude higher than the estimated
concentration of Mn in stormwater in MMT use areas (Section 8.3.4). Aerial deposition
of Mn-bound particles onto plants in MMT use areas is unlikely to reach concentrations
of concern.
Levels of Mn in soils (using the example of urban runoff in Sydney) are unlikely to
reach levels of concern. With the MMT use scenarios developed in Section 8.2, the
estimated concentration of Mn deposition from air to land is unlikely to result in
unacceptable soil Mn concentrations. In concentration areas such as stormwater, runoff
Mn may contain approximately 1.2 礸 Mn/L in high MMT use areas (using the Sydney
example from Section 8.3.4), several orders of magnitude less than phytotoxicological
benchmark for Mn in soil solution of 4 mg/L.
14.1.2 Aquatic risk
A PNECFreshwater for MMT of 0.014 mg/L has been derived based on the application of a
standard assessment factor of 10 to the lowest available NOEC data of 0.14 mg/L.
However, due to MMT's instability in the environment and subsequent low probability
of discharge to water bodies during normal use of fuels containing MMT, further
assessment of risk from MMT to aquatic organisms is not considered necessary.
PNECs for Mn in freshwater and marine waters of 1.7 and 0.8 mg/L, respectively, have
been derived (ANZECC and ARMCANZ, 2000; Section 14.5).
As indicated above, the PEC for Mn in stormwater derived from urban runoff may
approximate 0.0012 mg/L (refer Section 8.3.4).
Hazard quotients for estimated Mn discharge to freshwater and marine ecosystems from
urban runoff have been summarised below:
Predicted Environmental Predicted No Effect Hazard Quotient, HQ
Concentration of Concentration for Manganese,
Manganese, PEC (mg/L) PNEC (mg/L)
0.0012 PNECFreshwater 1.7 HQFreshwater 0.0007
0.0012 PNECMarine 0.8 HQMarine 0.0015
This evidence supports a conclusion of a low expected risk to the aquatic environment
from use of AVSR products containing MMT for the uses prescribed and the
volumetric use rates estimated. The abovementioned HQ values are based on current
estimated LRP demand (Present Use scenario), and risks are likely to reduce further as
demand for LRP decreases over time.
14.2 Occupational risk
A margin of exposure methodology is used frequently in international assessments to
characterise risks to human health (European Commission, 1996). The risk
characterisation is conducted by comparing quantitative information on exposure to the
NOAEL and deriving a Margin of Exposure (MOE) as follows:
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1. Identification of the critical effect(s);
2. Identification of the most appropriate/reliable NOAEL (if available) for the
critical effect(s);
3. Where appropriate, comparison of the estimated or measured human dose or
exposure (EHD) to provide a Margin of Exposure:
MOE = NOAEL/EHD;
4. Characterisation of risk, by evaluating whether the Margin of Exposure
indicates a concern for the human population under consideration.
The MOE provides a measure of the likelihood that a particular adverse health effect
will occur under the conditions of exposure. As the MOE increases, the risk of potential
adverse effects decreases. In deciding whether the MOE is of sufficient magnitude,
expert judgement is required. Such judgements are usually made on a case-by-case
basis, and should take into account uncertainties arising in the risk assessment process
such as the completeness and quality of the database, the nature and severity of effect(s)
and intra/inter species variability. Default uncertainty factors for intra- and inter-species
variability are usually 10-fold each and so a MOE of less than 100 is usually considered
a flag for concern.
14.2.1 Critical health effects
MMT
MMT is acutely toxic by all routes of exposure. The critical effects from acute exposure
to MMT are neurological and pulmonary dysfunction. In humans, giddiness, headache,
nausea, chest tightness, dyspnea and paresthesia are reported in anecdotal cases of acute
occupational exposure. Acute lethal exposure to MMT in animals is associated with
damage to the lungs, kidney, liver and spleen effects, tremors, convulsions, dyspnea
and weakness. In both animals and humans, slight skin and eye irritation results from
dermal and ocular exposure respectively.
Only limited repeated dose toxicity data are available. Repeated inhalation exposure to
MMT is reported to result in degenerative changes in liver and kidneys. A NOAEL of
0.0062 mg/L for inhalation exposure was reported. MMT did not cause teratogenic or
embryotoxic effects in developmental studies in rats.
Manganese
Given their production and widespread dissemination resulting from MMT combustion,
the present assessment also considers the health effects of Mn and inorganic Mn
compounds.
In animal studies, the critical effect following acute exposure to inorganic Mn
compounds is neurological dysfunction. Decreased activity, alertness, muscle tone,
touch response and respiration have been reported with oral administration. Pulmonary
effects are also reported in inhalation studies, but these may at least in part reflect an
inflammatory effect following inhalation of particulate matter rather than a result of
pulmonary toxicity of Mn.
Methylcyclopentadienyl manganese tricarbonyl (MMT) 91
In repeated dose animal studies, the critical effect is also neurological dysfunction.
Effects range from decreased motor activity to increased activity, aggression and
movement tremors. In humans, chronic occupational exposure to respirable dusts (2-22
mg/m3) leads to manganism, a progressive neurological disorder. Subclinical nervous
system toxicity has been detected in repeated occupational exposures ranging from
0.14-1.0 mg/m3. Reproductive effects including impotence and loss of libido in male
workers have also been associated with high Mn exposures. However, a dose-response
relationship for reproductive effects has not been established.
A principal epidemiological study of occupational inhalation exposure to Mn in which
neurobehavioural endpoints were examined (Roels et al., 1992) was used to determine a
dose-response relationship for neurological effects. A lower 95% confidence limit was
estimated at the level of Mn exposure expected to result in a 5% response rate. This
value (30 礸/m3) was considered a surrogate for a NOAEL for neurological effects. It is
important to base the risk characterisation on effects seen due to inhalational exposure,
as there appears to be differences in toxicity based on route of exposure and absorbed
dose.
14.2.2 Occupational health and safety risks
Although MMT is toxic by oral as well as dermal and inhalation routes, the likelihood
of exposure by ingestion in occupational settings is expected to be low. Similarly, the
low vapour pressure of MMT renders inhalation exposure to MMT vapours in
occupational settings unlikely. Exposure is possible, however, via dermal and ocular
routes and the toxicological profile of MMT indicates that contact with concentrated
solutions may result in local irritation. Irritation is also likely upon contact with fuels or
fuel additives containing MMT, but given the significant dilution of MMT with
petroleum distillates, this is likely to be due to the irritant properties of the petroleum
distillates more than the MMT itself.
Refineries
The blending of LRP is essentially an enclosed, automated process. Although exposure
via the dermal and ocular routes is possible from slops, spills and residue during
decanting of the imported MMT solution prior to LRP blending, exposure is expected
to be infrequent, minimal and of short duration. Overall, the potential for exposure to
MMT and hence Mn is low. Consequently, the risk to refinery workers from handling
MMT is assessed as low.
Formulators
Formulation of imported MMT into aftermarket fuel additives is essentially also an
enclosed, automated process that occurs even more intermittently than LRP blending.
In a similar fashion to LRP blending, exposure is possible via the dermal and ocular
routes from slops, spills and residue, but exposure would normally be minimal and of
short duration. The potential for exposure to MMT and hence Mn during formulation is
low. Consequently, the risk to formulation workers from MMT is assessed as low.
Petrol stations and maintenance workshops
Tanker drivers, petrol station attendants and auto mechanics may be exposed
occupationally to MMT through contact with additised fuels and less frequently with
Priority Existing Chemical Assessment Report Number 24
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aftermarket fuel additives containing MMT. Although exposure to fuel vapours may be
expected during a typical working day, the low vapour pressure of MMT and its high
dilution in fuel renders inhalation exposure to MMT unlikely. Exposure to MMT via
dermal and ocular routes is expected to be infrequent, minor and of short duration and
also limited due to its dilution with solvents and other additives in the fuel and fuel
additives. Therefore, the risk to these workers from MMT is assessed as low.
As reflected by overseas exposure data, auto mechanics at petrol stations and at
dedicated maintenance workshops may have particular potential for repeated exposure
to Mn from MMT and from Mn particulates associated with auto exhaust. Of overseas
studies examining Mn exposure of garage mechanics, the highest mean personal
exposure measured was 448 ng/m3 (Sierra et al., 1995) for auto mechanics working in
Montreal in mostly closed workshops (Section 8.5.1). Zayed et al. (1994) measured
mean personal exposure levels of 314 and 152 ng/m3 for garage mechanics in closed
and open workshops respectively.
Bearing in mind the limitations associated with extrapolating these overseas data to
local workplaces and given the likelihood that in the Sierra et al (1995) study only up to
one third of airborne Mn resulted from MMT combustion (Section 8.5.1), 148 ng/m3
(448 x 33%) is considered a worst case for Mn exposure from the use of MMT.
Assuming that all of the above Mn measured in the breathing zone of workers in the
closed garages will be deposited and absorbed, then:
Margin of Exposure = 30,000/148 = 203
This is considered a sufficient Margin of Exposure as it is probable that for Australian
auto mechanics the exposure to Mn would be much lower than calculated due to lower
use of MMT in fuel, differences in working conditions (i.e. less closure of workshops)
and the lower background levels of Mn in Australia. Therefore, the risk to these
workers from Mn exposure is considered to be low.
Car park personnel, professional drivers and road maintenance workers
Occupational exposure to Mn particulates from automotive exhaust may occur for these
workers but exposure is likely to be highly variable depending on the level of
separation from the exhaust sources and traffic densities. Personal exposure data for
Montreal taxi drivers show exposures that are lower than garage mechanics in the same
study by an order of magnitude (Zayed et al., 1994). Therefore, despite the lack of
personal exposure data for local workers, given the more restricted use of MMT and
lower environmental levels of Mn locally, exposure of Australian professional drivers
to MMT and Mn is likely to be significantly less than automechanics and so the risk to
local workers is considered low. Similarly, exposure to and risk associated with Mn for
car park and road maintenance workers is considered low.
14.2.3 Uncertainties
Uncertainties exist in the assessment of risk to local workers from MMT use as an
AVSR. No Australian personal exposure data exist and only overseas data from a small
number of limited studies are available and have been used for assessing risks
associated with exposures to MMT in the workplace. The interpretation of these data
for local conditions is complicated by factors such as differences in environmental
conditions such as climate that may affect, for example, the enclosure of workplaces
Methylcyclopentadienyl manganese tricarbonyl (MMT) 93
and therefore ambient air levels of MMT and Mn combustion products. Also, local use
patterns of MMT are likely to be significantly different to overseas where
supplementation of fuels with MMT is presently more prevalent.
There is also substantial uncertainty associated with the limitations in the amount and
quantity of toxicological data. For example, as there was no threshold for neurological
effects identified in the study by Roels et al. (1992) there is some uncertainty associated
with the derivation of surrogate NOAELs from this study. In addition, the study of
Roels et al. (1992) has some disadvantages in that it was an occupational
epidemiological study involving young or middle aged males and therefore
applicability to the general population, including women, infants, the elderly, and those
more susceptible because of illness, diet, or genetic predisposition, can only be
achieved by the use of uncertainty factors. The study of Roels et al. (1992) involved
exposure to Mn3O4 dust whereas recent data indicates that Mn sulphates and phosphates
as well as oxides are likely to be present in exhaust emissions as a result of MMT
combustion. Recent animal studies by Dorman et al. (2001) show that soluble Mn salts
such as Mn sulphate have toxicokinetics that differ from insoluble Mn compounds such
as Mn3O4, Studies by Vitarella et al. (2000b) and Brenneman et al (2000) show that Mn
can be transported to the brain via the olfactory bulb in rats. These authors note
significant differences in nasal and brain anatomy and physiology between rats and
humans that question the toxicological significance of this manganese absorption
pathway for humans. Therefore, there is also uncertainty related to potential differences
in toxicokinetics and potential toxicity of different Mn salts that may be associated with
human exposures to airborne Mn resulting from MMT combustion.
14.3 Public health risk
14.3.1 Acute effects
Direct public exposure to MMT is likely to occur primarily via the dermal route as a
result of spills and splashes of LRP and aftermarket products. MMT is not expected to
be a skin irritant at concentrations present in LRP. Dermal LD50's were in the range of
135-800 mg/kg bw (see Section 10.1) and an estimated dose received during exposure
under a worst-case scenario was approximately 208 礸/kg bw. Therefore it can be
concluded that there is a low risk of acute health effects in the general public as a result
of dermal exposure to MMT in LRP.
Regarding the potential for acute health effects following exposure to aftermarket
products containing MMT, skin irritation is not expected from exposure to MMT at the
concentrations present (< 10% w/w equivalent to approximately < 7% v/v). Assuming
that toxicokinetics and toxicodynamics of MMT are similar in rats and humans after
dermal exposure, a comparison of the dermal LD50s with the exposure estimates in
Section 8.6.1 suggests that there is some potential for acute health effects resulting from
dermal exposure to MMT in aftermarket products. However, the LD50 values in rats
were obtained after a constant 24-hour exposure to MMT and in contrast, much shorter
exposures are expected following spillage. Overall, the risk of acute health effects is
low given the small amounts to which people are likely to be exposed, the
concentration of MMT likely to be lower than 7% v/v (approximately 10% w/w) and
any spill on the skin is unlikely to reside untreated for long periods.
The risk of acute health effects as a result of accidental ocular exposure to MMT in
LRP and aftermarket products is considered to be low since exposure to very small
Priority Existing Chemical Assessment Report Number 24
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amounts is expected to occur only infrequently and MMT is not expected to cause eye
irritation at concentrations present in aftermarket products.
Acute health effects could also occur as a result of accidental ingestion by a child.
Acute oral LD50s were in the range of approximately 9-905 mg/kg bw (see Table 11)
with the rat being the most sensitive to the effects of MMT and having oral LD50s
generally in the range of about 20-60 mg/kg bw. Assuming that toxicokinetics and
toxicodynamics of MMT are similar in rats and humans after oral exposure and using
the lowest LD50 of approximately 10 mg/kg bw, a child (10kg) ingesting about one mL
of a product containing 10% w/w MMT could receive a potentially lethal dose.
Children between one and a quarter and three and a half years of age can swallow
approximately 4.5 mL of liquid (Gosselin et al., 1976), giving a potential dose several
times higher than the lowest oral LD50 observed in laboratory animals. Aftermarket
products are more likely to be stored in garages rather than in the home, these types of
products are generally not "attractive" for ingestion by a child and the information
provided by companies marketing these products states that they are supplied in
packages with child resistant closures. These factors could reduce the potential risk
associated with accidental ingestion of aftermarket products containing MMT.
However, since very small volumes provide a potentially lethal dose, products
containing MMT represent a significant acute health risk for children.
The risk to public health as a result of ingesting MMT in LRP is unlikely to be any
greater than the public health risk associated with ingestion of petrol without the
additive. Given the concentration of MMT currently in LRP (about 73mg/L), it can be
estimated that a 70 kg adult would need to ingest about 10 L of MMT-LRP in order to
receive a dose of MMT approaching the lowest acute oral LD50 observed in laboratory
animal studies. Similarly, it can be estimated that a child of 10 kg bodyweight and a
youth of about 35 kg bodyweight would need to ingest about 1 or 5 L respectively, of
MMT-LRP in order to receive doses approaching the lowest LD50. Therefore, acute
toxic effects as a result of accidental ingestion exposure to MMT in LRP are considered
to be unlikely.
14.3.2 Chronic effects
Total Mn exposures (from all sources combined) are unlikely to be significantly
changed by the use of MMT since exposure via food, water and other sources forms, by
far, the greatest proportion of the total dose and these sources of exposure are not
expected to change significantly as a result of the estimated use of MMT. However, the
data in Table 9 show that the use of MMT according to the Present Use scenario of
maintained LRP market share or 2004 scenario of diminished LRP market share will
potentially significantly increase the Mn dose received by inhalation (excluding
smoking).
The most significant adverse health effect from chronic (inhalation) exposure to Mn is
neurotoxicity. A variety of inhalation health standards and guidance values have been
promulgated in different countries based, in many cases, on an occupational
epidemiological study conducted by Roels et al. (1992). Workers examined in this
study demonstrated poor eye-hand coordination and hand steadiness and poor visual
reaction times after exposures to Mn dust in a battery factory.
Methylcyclopentadienyl manganese tricarbonyl (MMT) 95
From this study, the NOAEL for neurological effects in humans was established at 30
礸/m3 (Section 14.2.1) (WHO 1999). Converting intermittent exposures (5 days/week,
24 hours/day) to continuous exposures,
For Present Use scenario, where current LRP market share is maintained,
Margin of Exposure = (30 礸/m3 x 5/7 x 8/24)/4.9 ng/m3 = 1458
For 2004 scenario, where the LRP market share declines,
Margin of Exposure = (30 礸/m3 x 5/7 x 8/24)/2 ng/m3 = 3571
These margins of exposure are considered sufficient, taking into account conservative
exposure estimates.
Australian estimated ambient exposures are also below overseas chronic reference
values for Mn. Based on the study by Roels et al. (1992) and factoring for continuous
exposures, interindividual variations and uncertain pharmacokinetic information on
different Mn species especially regarding deposition in the brain, Wood and Egyed
(1994) for the Environmental Health Directorate, Health Canada derived an air
reference level of 110 ng/m3. Using uncertainty factors for continuous exposures,
interindividual variations, lack of data on developmental toxicity and toxicity of
different forms of Mn, the USEPA (1993) set an inhalation reference concentration
(RfC) at 50 ng/m3 based on the study by Roels et al. (1992). In a re-evaluation of
inhalation health risks associated with MMT in fuels in 1994, the USEPA derived
chronic reference concentrations in the range of 90-200 ng/m3 using a variety of
methodologies (USEPA 1994).
Factoring for continuous exposures, interindividual variations and developmental
effects in young children, WHO (1999) derived a guidance value of 150 ng/m3 for Mn,
based on the study of Roels et al. (1992). Similarly, and factoring for toxicity of
different Mn species and possible reproductive effects in females, ATSDR (2000)
devised a minimal risk level of 40 ng/m3. Although based on the same epidemiological
study, differences in these guidance values reflect differences in applied uncertainty
factors and derived starting values.
There is currently no Australian ambient air standard for Mn. Comparing the estimated
ambient air concentrations in Table 9 with the range of health standards set overseas
indicates that the estimated air concentrations for both the Present Use scenario and the
2004 scenario are unlikely to represent a significant risk to public health. Air
concentrations are much lower than the USEPA RfC for Mn, the guidance value
derived by the ASTDR and the standards developed by WHO and Wood and Egyed
(1994) for Health Canada.
The estimated ambient air concentrations of Mn due to MMT combustion are lower
than a range of ambient air standards and a number of apparently conservative
assumptions were used in the exposure assessment. Therefore, it could be concluded
that, the risk to public health as a result of the use of MMT (as outlined in the Present
Use scenario, Section 8.3.3 of this report) as an AVSR is expected to be low. However,
as outlined below, there is considerable uncertainty associated with this risk assessment
and there are likely to be sub-populations that have higher exposures and hence are at
greater risk than the general population. For example, exposure of people in Launceston
is of potential concern since the ambient air concentration of total (but not respirable)
Mn even without the contribution from MMT combustion is higher than some of the
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ambient air standards developed overseas and the use of MMT would add to
environmental Mn levels in this region.
14.3.3 Uncertainties
In the assessment of potential acute health effects, there is uncertainty associated with
the estimation of potential doses that may be received and extrapolation from animal
data to humans. There is likely to be considerable variation in doses received and toxic
responses are likely to vary both between species and among individuals within a
species.
Like uncertainties associated with occupational risk assessment, uncertainties involved
in the chronic health risk assessment are derived in part from significant database
limitations. There is a lack of suitable Australian air Mn data upon which to base a
realistic exposure assessment and there is very limited data that could be used to
determine the contribution that MMT combustion might make to ambient air levels of
respirable Mn. There are no Australian data on indoor concentrations of Mn and, since
Australians generally spend a significant amount of time indoors, the indoor
concentration of Mn could significantly influence personal exposures. In addition, there
are no Australian data for ambient air concentrations of Mn that could be used to
estimate exposures for individuals who live (or work) in areas with high traffic
densities and there are no data on air concentrations of Mn inside cars or in homes that
may have attached garages. Manganese concentrations in these microenvironments
could significantly influence public exposures.
Methylcyclopentadienyl manganese tricarbonyl (MMT) 97
15. Risk Management
15.1 Assessment of current control measures
According to the NOHSC National Model Regulations for the Control of Workplace
Hazardous Substances (NOHSC 1994c), exposure to hazardous substances should be
prevented or, when this is not practicable, adequately controlled, so as to minimise risks
to health and safety. The NOHSC National Code of Practice for the Control of
Workplace Hazardous Substances (NOHSC 1994) provides further guidance in the
form of a hierarchy of control strategies, namely, elimination, substitution, isolation,
engineering controls, safe work practices and personal protective equipment (PPE).
15.1.1 Elimination and substitution
Elimination is the removal of a chemical from a process and should be the first option
considered when minimising risks to health. In situations where it is not feasible or
practical to eliminate the use of a chemical, substitution should be considered.
Substitution includes replacing with a less hazardous substance or the same substance
in a less hazardous form.
As indicated in Section 7.2.1, there is a declining market for LRP sales and hence
AVSR additives due to attrition from the Australian motor fleet of vehicles designed to
run on leaded petrol.
By 2004, bulk sales of LRP are expected to decline to less than 5 % of total petrol sales
(Australian Petroleum Gazette, 1999). The general provision and sale of bulk LRP by
the oil refineries and terminals will become uneconomical at some point. This will
eliminate the requirement for refinery or terminal addition of MMT as an AVSR to
fuel.
When bulk LRP is phased out, aftermarket addition of AVSR fuel additives rather than
bulk treatment by the oil refineries and terminals will become the only option for
motorists with vehicles designed to run on leaded petrol. Given the likelihood of a base
population of vehicles for which mechanical alteration of engine components to run on
unleaded petrol may be prohibitive e.g. vintage vehicles, the total elimination of
AVSRs from the Australian fuel market is unlikely and the use of MMT as an
aftermarket additive may continue indefinitely.
Several AVSR additives that are potential substitutes for MMT are available on the
Australian market (Section 1.1). However, users need to consider the efficacy, cost,
health, safety and environmental effects of each in considering these as alternatives for
MMT.
15.1.2 Isolation and engineering controls
Isolation as a control measure aims to separate employees, as far as practicable, from
the chemical hazard. This can be achieved by distance, use of barriers or enclosure.
Engineering Controls are plant or processes which minimise the generation and release
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of hazardous substances. They include total or partial enclosure, local exhaust
ventilation and automation of processes.
Refineries and terminals
At refineries, MMT is isolated by containment of the MMT isotainer in a special
bunded enclosure distant from worker control areas. Engineering controls consist of
automatic metering of MMT from the isotainer through enclosed transfer lines to the
enclosed blending manifold and finished product tank and similar automatic, enclosed
transfer from the LRP finished product tank to terminals or to road tankers. The
connection to the dip leg of the isotainer to which transfer lines are fastened is located
at the top of the isotainer above fluid level, preventing inadvertent gravity flow and
spillage of MMT concentrate during manipulation.
The main isolation and engineering control measure in laboratory areas where quality
analyses are conducted is confinement of handling procedures to a ventilated fume
cupboard.
Third party formulators
At third party formulators, isolation of MMT occurs by the opening of import drums or
cylinders in bunded enclosures. Engineering controls for MMT during formulation
consist of pumping via enclosed transfer lines to a closed mixing or storage vessel and
subsequent enclosed feeding to automated filling/packing plant. Access bungs are
located at the top of the drums or cylinders above fluid level, preventing inadvertent
spillage through gravity flow of MMT concentrate during emptying.
In a similar fashion to refineries, the main isolation and engineering control measure in
laboratory areas where quality analyses are conducted is confinement of handling
procedures to a ventilated fume cupboard.
Petrol stations
At petrol stations, isolation and engineering controls of exposure for MMT are achieved
through enclosed transfer hoses for transferring LRP containing MMT from road
tankers and storage in underground tanks.
With regards to USTs, there are currently no existing leak prevention or detection
requirements for operators of underground fuel storage tanks in all states to detect and
control leakages from UST facilities. UST leak detection systems are implemented on a
voluntary basis by industry, particularly by major petroleum suppliers.
Aftermarket product use
Engineering controls of exposure for the public and occupational users of aftermarket
products containing MMT consist presently of containers with childproof screw caps
and long spouts. These long spouts enable sufficient insertion into the fuel filler of the
vehicle to minimise backflow and spillage during addition to unleaded fuel.
15.1.3 Safe work practices
Safe work practices are administrative practices that require people to work in safe
ways.
Methylcyclopentadienyl manganese tricarbonyl (MMT) 99
Refineries
Refineries operate under a permit-to-work system, which requires job safety audits
before work can commence. Professional occupational health and safety personnel
available on site typically oversee these. A HiTEC 3062 Product Handling Manual
supplied by Ethyl Corporation is used at refineries to provide guidance on storage
requirements, blending procedures, handling precautions, maintenance procedures and
decontamination and disposal procedures.
Third party formulators
The blending and packaging of aftermarket additives are conducted at formulator sites
in accordance with internal written standard operating procedures. These procedures
incorporate safety and quality control instructions, PPE requirements and first aid
directions.
15.1.4 Personal protective equipment
Refineries
The Ethyl Corporation HiTEC 3062 Product Handling Manual used by refineries
recommends personal protective equipment for use when handling bulk MMT solution.
For normal operations with good ventilation, PPE recommendations include safety
glasses or chemical goggles, face shield (when making or breaking connections), light
coloured overalls and neoprene, PVC or butyl rubber gloves and boots. In poorly
ventilated environments, an organic vapour cartridge respirator is recommended also.
In practice at the refinery, rubber gloves, nomex clothing, safety shoes goggles and
respirator with an organic vapour cartridge are used during connection and
disconnection of transfer lines with imported isotainers.
Third party formulators
PPE consisting of protective clothing, gloves and goggles are used during blending and
packaging of aftermarket additives.
Petrol stations and maintenance workshops
At petrol stations during unloading of road tankers and the dipping of underground
tanks, workers typically wear PPE consisting of protective clothing, footwear and
gloves. Auto mechanics with potential exposure to MMT in fuel also use PPE
consisting of protective clothing and footwear but gloves or protective eyewear are not
typically worn.
15.2 Hazard communication
15.2.1 Labels
Labels for six aftermarket MMT products containing up to 10% w/w MMT, one MMT
concentrate imported in bulk in isotainers and one MMT concentrate imported in drums
both containing approximately 60% w/w MMT were available for assessment. A label
for an additional imported drummed MMT concentrate was not available. Labelling for
this product consisted of an attached MSDS.
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Labels submitted for assessment were assessed for requirements under the NOHSC
National Code of Practice for the Labelling of Workplace Substances (NOHSC, 1994).
The assessment took the form of a qualitative appraisal of the following categories of
information:
? Substance identification;
? Hazard category/Signal word;
? ADG Code classification/packaging group;
? Details of manufacturer or supplier;
? Risk Information (or phrase);
? Safety Information (or phrase);
? Information on spills/leaks or fires; and
? Reference to MSDS.
In accordance with the hazard classification of MMT against the current version of the
NOHSC Approved Criteria for Classifying Hazardous Substances (NOHSC 1999a)
(Section 13), MMT is classified as a Hazardous Substance. Depending on the
concentration of MMT, labels for products containing MMT should contain the
following hazard classification, risk and safety phrases:
Classification of mixtures containing MMT
MMT Concentration Risk Phrases Classification of Mixture
0.1% - < 1% R20, R22 Harmful
1% - < 3% R23, R25, R48/20 Toxic
3% - < 7% R21, R23, R25, R48/20 Toxic
7% - < 10% R21, R26, R28, R48/20 Very Toxic
10% - < 25% R21, R26, R28, R48/23 Very Toxic
25% R24, R26, R28, R48/23 Very Toxic
The most appropriate safety phrases are:
? S36: Wear Suitable Protective Clothing;
? S38: In Case of Insufficient Ventilation Wear Suitable Respiratory Equipment.
Additional risk and safety phrases may also be applicable in products depending on the
presence of other hazardous ingredients.
MMT concentrates
Both labels available for assessment contained overseas but not local supplier contact
details, the product name and disclosed the presence of MMT. However, neither
Methylcyclopentadienyl manganese tricarbonyl (MMT) 101
contained information on ingredient proportions, either as an exact concentration or as a
range.
Signal words ("Warning" and "Danger: Poison") were found on both labels. As these
products are to be used in the workplace, the signal word should be "Hazardous". Only
one label contained information on an ADG code classification/packaging group.
Neither label contained the risk phrases recommended above. One label contained a
risk phrase of equivalent hazard warning for acute effects ("May be fatal if swallowed,
inhaled or absorbed through skin"). However, on this label there was no risk phrase
covering effects of repeated exposure. The second label contained an appropriate risk
phrase for repeated exposure ("May cause CNS, blood, liver and kidney damage after
prolonged or repeated exposure"), although this warning was in relation to another
ingredient in the mixture.
Neither label recommended the wearing of suitable protective clothing (S36) or the
wearing of suitable respiratory equipment in cases of insufficient ventilation (S38).
However, both contained adequate safety phrases regarding hazards of acute contact.
Both labels contained adequate first aid instructions but one label only contained advice
on spills/leaks.
Aftermarket products
In the case of labelling of hazardous substances of 500 mL capacity or less and where
space on the containers is especially limited, the NOHSC Labelling Code describes the
required minimum information as:
? Signal words and/or dangerous goods class;
? Product name; and
? Details of manufacturer or importer.
All labels for the present aftermarket products of 350 or 500 mL capacity contained
local supplier contact details and the product name. However, despite MMT being
above the cut-off of 0.1% in all products for classification as a hazardous ingredient,
only two labels disclosed the presence of MMT and none contained information on the
concentration of MMT present, either as an exact concentration or as a range.
Signal words were obvious only on 3 labels and no labels contained the risk or safety
phrases recommended above. Alternative safety phrases were present to varying
extents, pertaining to avoidance of dermal and ocular exposure, aspiration hazards or
prevention of child exposures. All labels included some first aid instructions varying
from advice regarding ingestion to additional advice regarding dermal exposure.
15.2.2 MSDS
Material Safety Data Sheets (MSDS) are the primary source of information for workers
involved in the handling of chemicals. Under the NOHSC National Model Regulations
for the Control of Workplace Hazardous Substances (NOHSC 1994c) and the
corresponding State and Territory legislation, suppliers of a hazardous chemical for use
at work are obliged to provide a current MSDS to their customers and employers must
ensure that an MSDS is readily accessible to employees with potential for exposure to
the chemical.
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A total of 8 MSDS, 5 for aftermarket products and 3 for imported MMT concentrates
were available for assessment against the NOHSC National Code of Practice for the
Preparation of Material Safety Data Sheets (NOHSC 1994b). The results of the MSDS
assessment are presented in Appendix 2.
On 6 MSDS, either no statement was found as to the hazardous nature of the product or
statements incorrectly claimed that the product was not hazardous (one MSDS). On 5
MSDS, an emergency telephone number was missing. Local company details were
missing on one MSDS.
Key health effects of MMT were included in the MSDS, although only 3 MSDS
mentioned the possibility of kidney damage. Also, the First Aid section of some MSDS
advised vomiting following ingestion whereas others advised (correctly) against
vomiting. On 6 MSDS, exposure standards drawn from overseas sources rather than
Australian sources (in this case they are the same) and there were no plain English
explanation as to what the skin notation on the exposure standard meant.
One MSDS for an MMT concentrate incorporated ingredient details for 3 different
possible formulations for the product targeted at the 3 different markets of USA,
Canada and Europe whilst not indicating the formulation applicable for Australia.
A sample MSDS prepared in accordance with the findings of this assessment and the
NOHSC National Code of Practice for the Preparation of Material Safety Data Sheets
(NOHSC 1994b) is provided in Appendix 3.
15.2.3 Education and training
Guidelines for the induction and training of workers exposed to hazardous substances
are provided in the NOHSC National Model Regulations for the Control of Workplace
Hazardous Substances (NOHSC 1994c). Under these regulations, employers are
obliged to provide training and education to workers handling hazardous substances.
These regulations stipulate that training and induction should be appropriate for the
workers concerned.
Refinery companies use the Ethyl Corporation HiTEC 3062 Product Handling Manual
specifying storage requirements, blending procedures, handling precautions,
maintenance procedures and decontamination and disposal procedures for refinery
blending.
15.3 Occupational monitoring and regulatory controls
15.3.1 Atmospheric monitoring
Under the NOHSC Model Regulations (NOHSC, 1994c), employers are required to
carry out an assessment of the workplace for all hazardous substances, the methodology
of which is provided in the NOHSC Guidance Note for the Assessment of Health Risks
Arising from the Use of Hazardous Substances in the Workplace (NOHSC, 1994d).
When assessment indicates that the risk of exposure via inhalation is significant,
atmospheric monitoring should be conducted to measure levels of the hazardous
substances in the workplace as a precursor to the implementation of suitable control
measures to reduce exposure. Subsequent monitoring is also required to ensure that
such measures are effective.
Methylcyclopentadienyl manganese tricarbonyl (MMT) 103
No atmospheric monitoring programmes for MMT in workplaces have been identified.
15.3.2 Occupational exposure standards
Australia as well as other countries has set exposure standards for MMT and elemental
and inorganic Mn.
Table 19. Occupational exposure limits for MMT and elemental and inorganic manganese
compounds
MMT Elemental and Inorganic Mn
Country 8 h TWA STEL 8 h TWA STEL
3 3 3
(mg/m3)
(mg/m ) (mg/m ) (mg/m )
0.2 (as Mn)* - 1 -
Australia
1 (Mn fume) 3 (Mn fume)
0.2* - 1 (fume) 3 (fume)
Belgium
0.2* - 2.5 -
Denmark
1 (fume)
0.2* 0.6* 2.5 -
Finland
1 (fume)
0.2* - 1 (fume) -
France
0.5 (inhalable
- - -
Germany
fraction)
0.2* 0.6* 5 (as Mn) -
Ireland
1 (Mn fume) 3 (Mn fume)
0.3 (except
- - -
Japan
inorganic
compounds)
0.2 (as Mn)* - 1 (as Mn) 3 (as Mn)
Netherlands
- - 5 -
The Philippines
0.3 (as Mn, 5 (as Mn, dusts
- -
Poland
dusts only) only)
- - - 0.2 (fume)
Russia
- - 2.5 -
Sweden
0.2* 5 -
Switzerland
1 (fume)
- - 5 -
Thailand
- - 5 (fume) -
Turkey
0.2 (as Mn)* 0.6 (as Mn)* 5 -
United
Kingdom 1 (Mn fume) 3 (Mn fume)
USA
0.2 (as Mn)* - 0.2 -
ACGIH
0.2 (Mn fume)
0.2 (as Mn)* - 1 3
NIOSH
1 (Mn fume) 3 (Mn fume)
- - 5 (Mn fume)
OSHA -
* skin notation
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Based on ACGIH (2000). NIOSH = National Institute of Occupational Safety and Health (recommended
limits). OSHA = Occupational Safety and Health Administration (statutory limits). STEL = short-term (15-
min) exposure limit. TWA = time-weighted average. United Kingdom STEL = short-term (10-min)
exposure limit. Germany STEL = short-term (30-min) exposure limit.
According to the NOHSC Exposure Standards for Atmospheric Contaminants in the
Occupational Environment, the current Australian national occupational exposure
standard for MMT (as Mn) is 0.2 mg/m3, expressed as an 8 h TWA airborne
concentration (NOHSC, 1995b). A skin notation, meaning that absorption through the
skin may be a significant mode of exposure, accompanies this value. In Australia, there
is no short-term exposure limit (STEL) for MMT. However, according to the NOHSC
Exposure Standards (NOHSC, 1995b) a process is not considered to be under
reasonable control if short-term exposures exceed three times the TWA exposure
standard for more than 30 minutes per 8 h working day, or if a single short-term value
exceeds five times the TWA exposure standard.
The Australian standard for Mn (as dust or fumes) is 1 mg/m3 expressed as an 8 h TWA
airborne concentration (NOHSC, 1995b). A short-term exposure limit (STEL) of 3
mg/m3 as Mn exists for Mn fumes (NOHSC, 1995b). The standards for MMT and Mn
as fumes were adopted from the ACGIH (1991) whilst that for Mn dust followed
review by the Exposure Standards Expert Working Group (NOHSC, 1995a).
15.3.3 Health surveillance
In accordance with NOHSC Model Regulations (NOHSC, 1994c), employers have a
responsibility to provide health surveillance in those workplaces where the workplace
assessment indicates that exposure to a hazardous substance may lead to an identifiable
substance-related disease or adverse health effect. MMT is not listed in Schedule 3 (list
of substances requiring health surveillance) and as such there are no formal
requirements for health surveillance programs for exposed workers.
No personal air monitoring or health surveillance programs have been reported in
Australia. According to the Ethyl Corporation Medical Guide for Use by Companies
Handling HiTEC 3062 Octane Booster, Ethyl Corporation recommends monitoring the
level of Mn in the urine of exposed workers as an indicator of MMT exposure and
considers that a level of Mn above 20 礸/L of urine might indicate exposure to Mn
from sources other than food. They consider urine Mn levels of up to 50 礸/L not an
immediate health concern, although if there is reason to suggest industrial exposure
related to the elevated reading, they recommend that the source should be found and
eliminated. Ethyl Corporation considers a urine Mn concentration above 50 礸/L strong
evidence for exposure to Mn and advises that any worker with such a urine Mn reading
be removed from the source of exposure, that the cause is identified and removed and
that the worker not be permitted to return to a job where exposure to MMT is possible
until two consecutive Mn urine measurements below 20 礸/L are registered.
15.3.4 National transportation regulations
Although MMT is not listed in the Australian Code for the Transport of Dangerous
Goods (ADG) Code, it meets the criteria for classification as a dangerous good, Class
6.1, Packing Group I (FORS, 1998). MMT can be ascribed a Proper Shipping Name
under the General Entry "Toxic Liquid, Organic, NOS" or Specific Entry "Metal
Methylcyclopentadienyl manganese tricarbonyl (MMT) 105
Carbonyls, NOS". The ADG Code containing guidance for the transport of dangerous
goods is therefore applicable for the transportation of MMT.
15.3.5 National storage and handling regulations
MMT meets the criteria for a dangerous good and so national storage and handling
regulations for dangerous goods are applicable for MMT. Storage and handling
requirements are described in the NOHSC National Standard for the Storage and
Handling of Workplace Dangerous Goods (NOHSC 2001a) and NOHSC National
Code of Practice for the Storage and Handling of Workplace Dangerous Goods
(NOHSC 2001b).
15.3.6 Control of major hazard facilities
According to the NOHSC National Standard for the Control of Major Hazard
Facilities (NOHSC, 1996), MMT is not one of the specifically identified chemicals that
must be considered when determining whether a site is a major hazard facility.
However, according to Tables 2 and 3 of the NOHSC National Standard for the
Control of Major Hazard Facilities, as MMT is classified as toxic, facilities that exceed
the threshold quantity of 200 tonnes of MMT qualify as a major hazard facility. The
purpose of this standard is to prevent and minimise the effects of major accidents and
near misses by requiring the person in control of the facility to:
? Identify and assess all hazards and implement control measures to reduce the
likelihood and effects of a major accident;
? Provide information to the relevant public authority and the community,
including other closely located facilities, regarding the nature of hazards of a
major hazard facility and emergency procedures in the event of a major
accident;
? Report and investigate major accidents and near misses, and take appropriate
corrective action; and
? Record and discuss the lessons learnt and the analysis of major accidents and
near misses with employees and employee representatives.
15.4 Public health regulatory controls
Since consumer (aftermarket) products containing MMT represent a potential public
health risk, some public health regulatory controls are warranted. MMT is not currently
included in a Schedule of the Standard for the Uniform Scheduling of Drugs and
Poisons (SUSDP). According to the Guidelines for National Drugs and Poisons
Schedule Committee (NDPSC), the acute toxicity profile for MMT is consistent with a
Schedule 7 entry in the SUSDP. The NDPSC may also consider appropriate cut-offs to
lower schedules to accommodate products containing MMT at lower concentrations. It
is recommended that consumer products containing MMT should be required to be
contained in packages with child resistant closures.
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15.5 Environmental regulatory controls
This section provides information with reference to international initiatives on the
environmental regulatory controls in Australia applicable to MMT and also Mn. In
summary, the management of environmental pollution and waste in Australia is
regulated through individual State and Territory regulatory systems rather than at a
National level and each State and Territory has legislative frameworks and strategies
for managing emissions and environmental pollution to air, land and waters.
15.5.1 Air quality management
Australia
Potential air quality issues from combustion of fuels containing MMT include exhaust
emissions of various Mn compounds (e.g. Mn oxides, Mn phosphate, Mn sulphate) and
small particles (estimated in the 0.056 to 3.1 祄 range; Roos et al., 2000).
Emissions of `air toxics' (defined below) in Australia are regulated through individual
State and Territory regulatory systems rather than at a National level and each State and
Territory has established legislative frameworks and strategies for monitoring and
managing air quality. National-level strategies are or have been developed to allow
consistent management of ambient air quality throughout Australia.
Air toxics are gaseous, aerosol or particulate pollutants that are present in the air in low
concentrations with characteristics such as toxicity or persistence so as to be hazardous
to human, plant or animal life. The terms `air toxics' and `hazardous air pollutants'
(HAPs) are used interchangeably. Air toxics include volatile and semi-volatile organic
compounds, polycyclic aromatic hydrocarbons, metals and aldehydes (NEPC, 2002).
Specific emission limitations and maximum ground level concentrations for individual
sources are used in some States to control emissions from industrial sources (NEPC,
2002).
Emissions of air toxics from new motor vehicles are controlled through Australian
Design Rules that set emission standards for a range of pollutants (not including Mn).
These standards are set at a National level rather than State or Territory level. Recently
the Australian Government introduced National fuel quality standards that will also
reduce the level of some air toxics in ambient air. Manganese is not regulated by these
standards and MMT is not listed currently on the register of prohibited fuel additives.
At a National level, at least two National Environment Protection Measures (NEPMs)
apply to air quality including the National Pollutant Inventory (NPI) NEPM (NEPC,
1998a) and the Ambient Air Quality NEPM (NEPC, 1998b). An additional NEPM
(Ambient Air Toxics) is also being developed (NEPC, 2002).
At a National level, particulates are included in the Ambient Air Quality National
Environment Protection Measure (NEPC, 1998b), which sets national standards for the
six air pollutants including airborne particles (as PM10, and PM2.5 is proposed to be
included). The National standard for particulates (as PM10) in ambient air is 50 礸/m3
(1 day average with 5 allowable daily exceedences per year), for implementation
throughout Australia by 2008 (NEPC, 2002).
Manganese compounds are not specifically included in either the Ambient Air Quality
NEPM (NEPC, 1998b) or the Ambient Air Toxics NEPM being developed (NEPC,
Methylcyclopentadienyl manganese tricarbonyl (MMT) 107
2002). An inventory of emissions of Mn and compounds, Mn fumes and particulate
matter (PM10) from significant emission facilities are included in the National
Pollutant Inventory NEPM (NEPC, 1998a). For the reporting period 2000 to 2001, the
NPI database indicates that those industrial reporting facilities throughout Australia that
provided data reported emissions of 140 tonnes of manganese to air, 30 tonnes to land
and 1100 tonnes to waters. Emissions from sources other than reporting facilities
(smaller companies and non-industrial sources) for the same period totalled an
additional 380 tonnes of manganese to air. Total air emissions to the Sydney, Newcastle
and Wollongong airshed (2000-2001 period) consisted of 15 tonnes of manganese.
Although the NPI database contains air, land and water emissions data for manganese
from some NPI reporting facilities, the current year (2001-2002) is the first reporting
period for facilities meeting a reporting criteria for manganese and manganese
compounds (ie. use of >10 tonnes per annum) and so many more industrial emissions
sources are expected to report for this period. The emissions data for the reporting
period 2001-2002 will be available in early 2003.
International air quality management
Several international organisations have introduced regulations or policies that aim to
limit the exposure of the general public to air particulates. This is relevant to the use of
MMT as an AVSR as combustion of MMT results in particulate inorganic Mn
compounds. The Organisation for Economic Cooperation and Development has
implemented the Advanced Air Quality Indicators and Reporting Project in OECD
member countries, including Australia (OECD, 1999). The project focuses on six major
urban air pollutants, including particulate matter.
In the United States, air quality is managed and regulated under the Clean Air Act
(CAA) 1970. The National Air Toxics Program: The Integrated Urban Air Strategy
outlines a strategy for addressing cumulative health risks from identified HAPs,
including Mn compounds in urban areas (USEPA, 1999). The Strategy also establishes
air monitoring requirements for motor vehicle emissions including vehicles using fuels
containing MMT and sets standards for HAPs emitted from motor vehicles and fuels.
In Canada, a range of air toxics including particulates PM10 and PM2.5 are measured
and analysed within the National Air Pollution Surveillance (NAPS) Network. The
NAPS network was established in 1969 to monitor and assess the quality of ambient air
in Canadian urban areas.
In the United Kingdom, airborne particulates are managed by the Department of
Environment, Transport and Regions (UKDETR), which established a benchmark
standard for particles in air.
15.5.2 Aquatic ecosystem management
The Australian water quality guidelines (ANZECC and ARMCANZ, 2000), established
under the National Water Quality Management Strategy, provide water and sediment
quality guidelines (trigger levels) for freshwater and marine ecosystems throughout
Australian States and territories. The guidelines provide a decision-tree framework for
the assessment and management of risks from chemicals to water and sediment quality.
No trigger values are available for MMT; however, ANZECC and ARMCANZ (2000)
provide an ambient trigger level for Mn for the protection of freshwater ecosystems of
1.7 mg/L. Insufficient toxicity data were available from marine organisms for
Priority Existing Chemical Assessment Report Number 24
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ANZECC and ARMCANZ (2000) to derive a marine trigger value. Therefore
ANZECC and ARMCANZ (2000) have derived a marine interim indicative working
level (IIWL) of 0.8 mg Mn/L. Each State and Territory has legislative frameworks and
strategies for managing water pollution.
15.5.3 Disposal and waste treatment
Each Australian State and Territory provides statutory controls on waste generation and
management. MMT and Mn-containing materials classified as wastes should be sent to
licensed waste disposal contractors in accordance with State and Territory
requirements. No specific waste disposal guidelines, standards or management issues
were identified for MMT or Mn wastes. Due to the toxicity of MMT, care should be
exercised in disposing of contaminated wastes to avoid pollution of the environment.
For example, in NSW, transporters conveying MMT waste in quantities greater than
200 kg per load or waste facilities treating MMT waste require a licence under the
Protection of the Environment Operations Act (1997) issued by the NSW EPA.
15.6 Emergency procedures
Fire and spill responses for MMT are included in MSDS for bulk HiTEC 3062 (Ethyl
Corporation) and drummed MMT concentrates TK-660 (Nulon Products Australia Pty
Ltd) and Wynn's Octane Booster Concentrate. Emergency response information is also
available from ILO (1999), NIEHS (2001) and the Ethyl Corporation HiTEC 3062
Octane Booster Product Handling Guide (2001).
Recommendations from the Ethyl Corporation Product Handling Guide for dealing
with fire or spills of HiTEC 3062 consisting of 62% MMT in petroleum distillate (and
applicable for the similar drummed MMT concentrates) state:
Personnel
? Personnel engaged in cleanup operations should be equipped with clothing and
protective gear as suggested in the MSDS ?chemical resistant gloves, suit and
boots and safety glasses with side shields;
? For minor spills, respirators must be worn; for significant spills, air-supplied
respiratory equipment or self-contained breathing apparatus is required.
Small spills and leaks
? Use absorbent materials to remove free liquid from the spill area;
? Clean smooth contaminated areas with a solvent, such as kerosene and collect
rinsate with absorbent materials;
? Remove contaminated soils and/or absorbents with appropriate tools such as
shovels;
? Thoroughly scrub smooth contaminated areas with soap and water.
Large spills
? Take immediate action to stop, contain and isolate the spill;
Methylcyclopentadienyl manganese tricarbonyl (MMT) 109
? Eliminate all sources of ignition;
? Barricade and restrict unauthorised personnel from the general area;
? Notify regulatory authorities immediately in the event of imminent danger to
human health or to the environment;
? Contain spills with dykes or absorbent material to prevent migration and entry
into sewers or streams;
? Use water sprays to reduce vapours. Avoid flushing the liquid into a stream or
an open sewer system. Blanketing the spill with high-density (low expansion
type) foam is also effective to reduce evaporation. Commercial absorbents,
activated charcoal, petroleum coke or fine soils can also be used to contain and
collect the spill and reduce evaporation;
? Pump all possible liquid from the spill area into steel closed-head drums or
other suitable metal containers that can be sealed;
? Finish collecting residual spilled material with absorbents. Remove
contaminated soils and/or absorbents with appropriate tools and place in sealed
metal containers or drums.
Fire response
Use foam, water spray or dry chemicals to extinguish.
Priority Existing Chemical Assessment Report Number 24
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16. Discussion and Conclusions
MMT has been introduced recently onto the Australian market as an anti-valve seat
recession additive and MMT used for this purpose is the subject of the present
assessment. AVSR fuel additives are added to fuel to prevent excessive valve seat wear
and consequent recession into the automotive engine head. Until its phase out,
tetraethyl lead was the most common AVSR additive.
With the national phase out of lead in petrol, there are now four types of AVSR
additives presently marketed in Australia. MMT, phosphorus-based and sodium-based
AVSRs are presently being assessed by NICNAS as Priority Existing Chemicals and a
potassium-based AVSR was assessed by NICNAS as a New Industrial Chemical. These
AVSRs are delivered either pre-blended into LRP or are available as an aftermarket
fuel supplement for addition to unleaded fuel by consumers.
Due to commercial sensitivities of information on market share for individual AVSRs,
exposure and risk assessments for each individual AVSR assume 100% market share.
Additionally, given that the use of AVSRs is governed by a declining population of
older vehicles requiring these fuel additives, risk assessments were conducted under
two separate scenarios based on AVSR use patterns. The first scenario "Present Use"
assumes a continuation of the present LRP market of 2500 ML per year with 90% of
AVSRs delivered in bulk LRP and 10% delivered as aftermarket fuel additives. The
second scenario "2004" assumes a decline of the LRP market to 1000 ML with the
AVSR delivered totally as an aftermarket fuel additive. These scenarios are based on
motor vehicle statistics and forecasts from the Australia Bureau of Statistics and
Australian Institute of Petroleum. The occupational health and safety, public health and
environmental consequences of these volumes and modes of delivery of AVSRs are
considered accordingly.
MMT is manufactured overseas and assuming MMT has 100% of the AVSR market,
less than 180 tonnes is being imported to Australia per year. The majority of this
amount is used to blend LRP, with only a minor quantity (< 10 tonnes/year) used for
the formulation of aftermarket fuel additives. Concentrated MMT (approximately 60%
MMT w/w) is imported in bulk for formulation into LRP containing a recommended
72.6 mg MMT/L (approximately < 0.01% MMT w/w) and formulation of aftermarket
products containing < 150 mg MMT/L (< 10% w/w MMT). A small amount is also
imported in pre-packaged aftermarket products containing < 10% w/w MMT.
16.1 Health hazards
In fuel, MMT is combusted and converted to a mixture of Mn oxides such as Mn3O4
and salts including Mn phosphate (Mn3[PO4]2) and Mn sulphate (MnSO4). A proportion
of these inorganic derivatives are released in association with particulate material in
vehicle exhaust. The balance (around 80%) is accumulated in engines or exhaust
systems. Therefore, the health hazards associated with the use of MMT also include
those associated with inorganic Mn compounds.
MMT is acutely toxic by all routes of exposure. The critical effects from acute exposure
to MMT are neurological and pulmonary dysfunction. In humans, giddiness, headache,
Methylcyclopentadienyl manganese tricarbonyl (MMT) 111
nausea, chest tightness, dyspnea and paresthesia are reported in anecdotal cases of acute
occupational exposure. Acute lethal exposure to MMT in animals is associated with
damage to the lungs, kidney, liver and spleen effects, tremors, convulsions, dyspnea
and weakness. In both animals and humans, slight skin and eye irritation results from
dermal and ocular exposure respectively.
Limited data show that repeated inhalation exposure to MMT in animals results in
degenerative changes in liver and kidneys. A NOAEL of 0.0062 mg/L for inhalation
exposure was reported.
Manganese has been the subject of several extensive reviews and the summary of Mn
toxicity for this present report is based predominantly on the WHO Concise
International Chemical Assessment Document - Manganese and Its Compounds. In
humans, Mn is an essential element. In animal studies, the critical effect following
acute exposure to inorganic Mn compounds is neurological dysfunction. Decreased
activity, alertness, muscle tone, touch response and respiration have been reported with
oral administration. Pulmonary effects are also reported in inhalation studies, but these
may at least in part reflect an inflammatory effect following inhalation of particulate
matter rather than a result of pulmonary toxicity of Mn.
In repeated dose animal studies of Mn toxicity, the critical effect is also neurological
dysfunction, and effects range from decreased motor activity to increased activity,
aggression and movement tremors. In humans, chronic occupational exposure to
respirable Mn dusts is associated with subclinical nervous system toxicity through to
overt manganism, a progressive neurological disorder. Reproductive effects including
impotence and loss of libido in male workers have also been associated with high Mn
exposures.
It is generally agreed that the critical study for neurological effects due to Mn exposure
is Roels et al., (1992). This principal neuroepidemiological study of occupational
inhalation exposure to Mn was used by WHO (1999) to determine a dose-response
relationship for neurological effects. A lower 95% confidence limit was estimated for
the level of Mn exposure expected to result in a 5% response rate. This value (30
礸/m3) was considered a surrogate for a NOAEL for neurological effects in the present
assessment.
MMT (as Mn) is currently listed in the NOHSC List of Designated Hazardous
Substances (NOHSC, 1999b) with no classification. In accordance with the NOHSC
Approved Criteria for Classifying Hazardous Substances (NOHSC, 1999a), It is
recommended that MMT is classified "Hazardous" with the following risk phrases:
? R26 - Very Toxic by Inhalation;
? R28 ?Very Toxic if Swallowed;
? R24 ?Toxic in Contact with Skin;
? R48/23 ?Toxic: Danger of Serious Damage to Health by Prolonged
Exposure Through Inhalation.
As a result of this classification, the following additional safety phrases are also
recommended:
? S36 ?Wear Suitable Protective Clothing;
Priority Existing Chemical Assessment Report Number 24
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? S38 ?In Case of Insufficient Ventilation Wear Suitable Respiratory
Equipment.
Based on a toxicity profile from animal experiments, MMT meets the criteria of the
ADG Code (FORS, 1998) for classification as a toxic substance Class 6.1, Packing
Group I. MMT can be ascribed a Proper Shipping Name using the General Entry
"Toxic Liquid, Organic, NOS" or Specific Entry "Metal Carbonyls, NOS". MMT is
currently not listed in the SUSDP. However, according to the Guidelines for the
National Drugs and Poisons Schedule Committee, its domestic use and toxicity profile
are also consistent with a Schedule 7 entry in the SUSDP. Consequently, this report
will be referred for consideration of scheduling by the NDPSC.
16.2 Environmental hazards and risks
MMT is highly toxic to aquatic organisms and spill incidents and leaks to water bodies
and land should be managed through existing Federal, State and Territory legislative
frameworks and protocols to mitigate adverse effects to the aquatic environment. Such
incidents may potentially occur during shipment into Australia, bulk handling and
storage and leakage of underground storage tanks.
All States and Territories have general environment protection legislation pertaining to
pollution and contaminated land. However, there are currently no existing leak
prevention or leak detection requirements for operators of underground fuel storage
tanks in NSW, and probably other States and Territories, to detect and control leakages
from UST facilities. UST leak detection systems are implemented on a voluntary basis
by industry, particularly by major petroleum suppliers.
Use of MMT in internal combustion engines as a fuel additive and subsequent
degradation through combustion, and its short persistence in the environment, indicate
that aquatic and terrestrial organisms are unlikely to be exposed to MMT at or above
levels of concern through existing use as an AVSR. A low environmental risk is
predicted.
Manganese, the principle degradation by-product from combustion of MMT, is
naturally occurring and ubiquitous in the environment. It is an essential nutrient of
plants and animals. Environmental exposure to Mn compounds will mostly arise
through the gaseous phase. Eventually, these will deposit to land and waters. The
emission of Mn into the environment from use of fuels containing MMT is unlikely to
develop to levels of concern and therefore poses a low risk for terrestrial or aquatic
environments.
The findings of this assessment highlight the potential for leaking USTs to pose an
unacceptable risk to the environment. Such leakages represent localised, point source
discharge, but have the potential to detrimentally affect significant areas of the
environment. Although a large number of USTs have been replaced or have had leak
detection systems or other measures installed, most USTs do not have leak detection
systems, and many that are currently in service are old and have the potential to leak in
the future if not decommissioned or replaced.
Although there is potential for risk to the environment from leakage of fuel (which may
or may not contain MMT) from USTs, the risk would be site specific.
Methylcyclopentadienyl manganese tricarbonyl (MMT) 113
There is currently no environmental hazard classification system in Australia. In
accordance with the OECD Globally Harmonized System of Classification and
Labelling of Chemicals, MMT would be classified Chronic 1 Very Toxic to Aquatic
Life with Long-lasting Effects (OECD, 2002).
16.3 Occupational health and safety risks
Occupational exposure to MMT mainly via the dermal route may be envisaged for
refinery and formulator workers during blending of LRP or aftermarket fuel additives.
Occupational exposure to MMT is possible also for those workers in downstream
processes that handle fuel, fuel additives and automotive fuel system components e.g.
petrol station and automotive maintenance workers. In addition, occupational exposure
to Mn, mainly via inhalation, is possible for these and other workers associated with or
in the vicinity of automotive usage e.g. service station attendants, professional drivers,
car park and road maintenance personnel.
Although MMT is toxic by oral, dermal and inhalation routes, the enclosed processes
used predominantly for blending of fuel or fuel additives where concentrates are
handled renders the possibility of exposure low. Mild irritation is possible upon contact
with fuels or fuel additives containing MMT but given the significant dilution of MMT
with petroleum distillates, irritation is likely due to the irritant properties of the
petroleum distillates more than the MMT itself.
Exposure to MMT is possible during handling of additised fuels, fuel additives and
automotive fuel system components but is expected to be infrequent, minor and of short
duration and limited due to its dilution with solvents and other additives in the fuel and
fuel additives. Overall, the risks to workers posed by MMT during formulation and
during handling of fuels, fuel additives containing MMT and automotive fuel system
components contaminated with MMT is low.
The main route of exposure to Mn particulates is inhalation and in occupations where
automotive usage is ubiquitous, chronic inhalation of inorganic Mn species may result.
A worst-case scenario was considered for Mn exposure of Australian auto mechanics
from the use of MMT. Using overseas personal inhalational exposure estimates, a
Margin of Exposure of 203 for local mechanics was derived. This is considered a
sufficient Margin of Exposure given the conservative exposure estimates derived from
data from Canada where MMT is used widely as an octane enhancer in fuels and
ambient air levels of Mn are higher and calculations assuming 100% market share for
MMT. Therefore, the occupational health risks associated with Mn exposure from
MMT combustion are assessed as low.
MSDS and labels for imported MMT concentrates and formulated aftermarket additives
were assessed qualitatively against the NOHSC MSDS and Labelling Codes. In
general, labels were lacking ingredient information and although some relevant hazard
warnings were present, the recommended risk and safety phrases from this assessment
were missing. Signal words and disclosure of the presence of MMT were also missing
from some labels. Local contact details were absent from labels of imported
concentrates. MSDS in general contained relevant health effect information but also did
not include recommended risk and safety phrases. Most also had other important
elements missing such as correct hazard statements and emergency telephone numbers.
A sample MSDS for MMT is included in Appendix 3.
Priority Existing Chemical Assessment Report Number 24
114
MMT (as Mn) is listed in the NOHSC Exposure Standards for Atmospheric
Contaminants in the Occupational Environment with an exposure standard of 0.2
mg/m3, (8 h TWA), skin notation (NOHSC 1995b).
16.4 Public health risks
Direct public exposure to MMT is likely to occur primarily via the dermal route as a
result of spills and splashes of LRP and aftermarket products.
In LRP, MMT is not expected to be a skin irritant at present concentrations. Estimated
dermal doses of MMT to be received under a worst case scenario of LRP spillage were
several orders of magnitude below comparable animal dermal LD50s. Therefore, there
is a low risk of acute health effects for the general public as a result of dermal exposure
to MMT in LRP.
Similarly, in aftermarket products, MMT at concentrations presently reported is not
expected to be a skin irritant. A comparison of dermal LD50 values with exposure
estimates suggests some potential for acute toxicity resulting from dermal exposure to
MMT in aftermarket products. However, LD50 values in rats were obtained after a
constant 24-hour exposure to MMT and in contrast, much shorter exposures are
expected following spillage. Overall, the risk of acute dermal effects in consumers is
low given the small amounts of additive to which people are likely to be exposed, the
low concentration of MMT present with the fuel additive and that any spill on the skin
is unlikely to reside untreated for long periods.
The risk of acute health effects as a result of accidental ocular exposure to MMT in
LRP and aftermarket products is also considered to be low since exposure to very small
amounts of product is expected to occur only infrequently and MMT is not expected to
cause eye irritation at low concentrations present in these products.
Acute health effects could occur as a result of accidental ingestion of MMT by a child
or by adults when siphoning fuel. The health risk to adults from accidental ingestion of
LRP containing MMT during siphoning or to children following ingestion of LRP
stored inappropriately around the home is considered low, given the low level of MMT
(< 0.01% w/w) in LRP. However, assuming comparable toxicokinetics of MMT in rats
and humans after oral exposure and using the lowest rat LD50 for MMT of
approximately 10 mg/kg bw, a child (10kg) ingesting about one mL of an aftermarket
product containing 10% w/w MMT could receive a potentially lethal dose. Children
between one and a quarter and three and a half years of age can swallow approximately
4.5 mL of liquid, giving a potential dose several times higher than the lowest oral LD50
observed in laboratory animals.
The potential risk associated with accidental ingestion of aftermarket products
containing MMT is lessened by the likely storage of aftermarket products in garages,
products being generally not "attractive" for ingestion by a child and products as
assessed packaged with child resistant closures. However, since very small volumes
provide a potentially lethal dose, products containing MMT represent a significant
acute health risk for children.
Manganese is a ubiquitous element and chronic Mn exposures (from all sources
combined) are unlikely to be significantly changed by the use of MMT. Exposure via
food and water forms, by far, the greatest proportion of the total human Mn dose, and
are not expected to change significantly as a result of the estimated use of MMT.
Methylcyclopentadienyl manganese tricarbonyl (MMT) 115
However, MMT used according to the Present Use scenario of maintained LRP market
share or the 2004 scenario of diminished LRP market share will potentially
significantly increase the Mn dose received by inhalation (excluding smoking).
Based on the study of Roels et al (1992), the NOAEL for neurological effects in
humans was established at 30 礸/m3 and Margins of Exposure were calculated in this
report converting intermittent Mn exposures (5 days/week, 24 hours/day) to continuous
exposures. For the Present Use scenario, where current LRP market share is maintained
with a calculated ambient air concentration for Mn of 4.9 ng/m3, the Margin of
Exposure was calculated at 1458. For the 2004 scenario, where the LRP market share
declines with a calculated ambient air concentration for Mn of 20 ng/m3, the Margin of
Exposure was calculated at 3571. These Margins of Exposure are considered sufficient,
taking into account the conservative exposure estimates used.
It is noted that the estimated ambient air concentration of Mn due to MMT combustion
is at the lower end of a range of overseas inhalation health standards and guidance
values. However, a number of conservative assumptions were used in this present
exposure assessment. Consequently, the risk to public health as a result of the use of
MMT as an AVSR is expected to be low. However, there are uncertainties associated
with this risk assessment and there are likely to be sub-populations that have higher
exposures and hence are at greater risk than the general population. For example,
although the measured ambient air concentration of respirable Mn is probably unrelated
to the use of MMT, exposure of people in Launceston is of potential concern since the
ambient air concentration of total (but not respirable) Mn in that city is higher than
some of the ambient air standards developed overseas. The use of MMT would add
potentially to environmental Mn levels in this region.
16.5 Data gaps
For the purposes of risk assessment, this report identified a number of significant data
gaps. These include:
? data on potential skin or respiratory sensitisation and effects associated with
chronic MMT exposure;
? definitive information on the speciation of Mn compounds emitted during
MMT combustion under different driving conditions;
? the toxicokinetics and potential adverse effects of different inorganic Mn
compounds resulting from the combustion of MMT;
? health effects associated with chronic, low level Mn exposure, especially in
susceptible populations such as children or individuals with compromised liver
function; and
? Australian exposure data (personal and ambient air monitoring data) for
determining public exposures to Mn especially in environments such as
indoors, inside cars, areas of high traffic density and areas with Mn emitting
industries.
This report notes certain projects planned or underway that will address some of these
data gaps. For example the project entitled "Metal Emissions from Petrol and the
Future Health of Children" by Macquarie University Graduate School of the
Priority Existing Chemical Assessment Report Number 24
116
Environment, Australian Government Analytical Laboratories, Commonwealth
Scientific and Industrial Research Organisation, United States Environmental
Protection Agency and Australian Nuclear Science and Technology Organisation is
presently examining fuel-related Mn emissions on susceptible subpopulations. Also,
Environment Australia are planning a project entitled "Fine Particle Composition in
Four Major Australian Cities" where the sampling, elemental and chemical
compositional analysis of PM10 and PM2.5 particles including analysis for manganese in
major Australian cities will be conducted.
Methylcyclopentadienyl manganese tricarbonyl (MMT) 117
17. Recommendations
This section provides the recommendations arising from the priority existing chemical
assessment of MMT. Recommendations are directed principally at regulatory bodies
and importers and formulators of MMT and MMT products. Implicit in these
recommendations is that best practice is implemented to minimise occupational and
public exposure and environmental impact.
17.1 Recommendations for regulatory bodies
17.1.1 NOHSC
MMT (as Mn) is currently listed in the NOHSC List of Designated Hazardous
Substances (NOHSC, 1999b) with no classification.
In accordance with the NOHSC Approved Criteria for Classifying Hazardous
Substances (NOHSC, 1999a), MMT is classified "Hazardous" with the following risk
phrases:
? R26 ?Very Toxic by Inhalation;
? R28 ?Very Toxic if Swallowed;
? R24 ?Toxic in Contact with Skin;
? R48/23 ?Toxic: Danger of Serious Damage to Health by Prolonged
Exposure Through Inhalation.
The following safety phrases are also recommended for MMT:
? S36 ?Wear Suitable Protective Clothing;
? S38 ?In Case of Insufficient Ventilation Wear Suitable Respiratory
Equipment.
It is recommended that this classification for MMT be adopted by NOHSC as part of
their process for updating the List of Designated Hazardous Substances (NOHSC
1999b).
17.1.2 National Drugs and Poisons Schedule Committee
Given the acute toxicity profile of MMT and the potential for consumer exposure to
products containing MMT, it is recommended that the NDPSC consider scheduling of
MMT in the Standard for the Uniform Scheduling of Drugs and Poisons. A copy of the
final report will be forwarded to the NDPSC for their consideration.
17.1.3 Tasmanian Department of Primary Industries, Water and Environment
This report notes a pilot study of atmospheric particulates conducted prior to the use of
MMT in automotive fuels that cites elevated atmospheric manganese levels in
Priority Existing Chemical Assessment Report Number 24
118
Launceston, Tasmania at certain periods compared to other cities. Given the potential
for the combustion of MMT in automotive fuels to add to atmospheric manganese
levels, a copy of this report will be forwarded to the Tasmanian Department of Primary
Industries, Water and Environment for their consideration.
17.2 Recommendations for MMT importers and formulators of MMT products
17.2.1 Hazard communication ?MSDS
This assessment found that MSDS for products containing MMT did not conform to the
requirements of the NOHSC National Code of Practice for the Preparation of Material
Safety Data Sheets (NOHSC 1994b). In order to ensure conformity with this code, it is
recommended that importers of MMT review their MSDS for compliance and pay
particular attention to the following points:
? risk phrases and hazard information should be updated to reflect the hazard
classification in Recommendation 17.1.1;
? MSDS should carry correct hazard statements;
? emergency telephone numbers should be included; and
? the Australian exposure standard for MMT should be listed with an explanation
for skin notation; and
? only ingredients relevant to the product should be included.
A sample MSDS can be found in Appendix 3.
17.2.2 Hazard communication ?labels
This assessment found that labels for MMT products did not conform to the
requirements of the National Code of Practice for the Labelling of Workplace
Substances (NOHSC 1994a) or the Australian Dangerous Goods Code. In order to
ensure conformity with these codes, it is recommended that importers of MMT review
their labels for compliance and pay particular attention to the following points:
? risk phrases and hazard information should be updated to reflect the hazard
classification in Recommendation 17.1.1;
? safety phrases should be included as noted in Recommendation 17.1.1;
? contact details of the local supplier should be included;
? hazard category or signal words should be included; and
? labels should be attached to product containers.
17.2.3 Packaging
It is recommended that all consumer products containing MMT be packaged in
containers with childproof closures.
Methylcyclopentadienyl manganese tricarbonyl (MMT) 119
To prevent backflow and spillage of MMT by consumers when using aftermarket MMT
products, it is also recommended that all consumer products designed to be added
directly to fuel tanks should be enclosed in containers with spouts of sufficient length to
ensure good insertion of the spout into the fuel filler.
If products containing multiple shots of additive are produced for consumer use, it is
recommended also that where possible these should be packaged in containers with a
measuring capacity or ideally with an automatic measuring and dispensing capacity.
Appropriate consideration of the light sensitivity of MMT would also be required.
17.2.4 Emergency procedures
Any spills of product containing MMT should not be allowed to enter stormwater,
sewers or natural waters.
Priority Existing Chemical Assessment Report Number 24
120
18. Secondary Notification
Under Section 64 of the Industrial Chemicals (Notification and Assessment) Act 1989,
the secondary notification of a chemical that has been assessed under the Act may be
required where an introducer (manufacturer or importer) of a chemical becomes aware
of any circumstances that may warrant a reassessment of its hazards and risks. In the
case of MMT, specific circumstances include:
? use of MMT in bulk transport fuels other than LRP;
? the manufacture of MMT has begun in Australia;
? additional information has become available to the introducers as to adverse
health and/or environmental effects of MMT;
The Director (Chemicals Notification and Assessment) must be notified within 28 days
of the introducer becoming aware of any of the above or other circumstances prescribed
under Section 64(2) of the Act.
Methylcyclopentadienyl manganese tricarbonyl (MMT) 121
Appendix 1 - Calculation of LRP Volumes
for 2004
The weekly fill-up rate for vehicles using lead replacement petrol (LRP) was calculated
from sales volumes of lead and lead replacement petrol (LRP) in July 2000 to June
2001 of 2 937.36 ML (Department of Industry, Science and Research, 2001) and from
the number of vehicles using leaded petrol at 31 March 2001 of 2 904 342 (Australian
Bureau of Statistics Motor Vehicle Census, 2001) as:
2 937.36 x 106 litres/year ?2 904 342 vehicles = 1 011 litres/year/vehicle
= 19.4 litres/week/vehicle
LRP volumes in 2004 for 1 000 000 VSR susceptible vehicles were calculated by using
a 19.4 litre LRP fill-up rate per week per vehicle, i.e., 1011 litres/year:
1 000 000 vehicles x 1011 litres/year/vehicle = 1 011 000 000 litres/year
1 000 ML/year of LRP in 2004
Priority Existing Chemical Assessment Report Number 24
122
Appendix 2 - MSDS Assessment Summary
Information Number of MSDS Comments
containing correct
information
Introductory And Company Details
Date of issue (mon/year) 8/8 Two MSDS had dates in the
wrong format.
Statement of hazardous nature 2/8 Of the remainder, 4/8 had a
statement that the product was
not hazardous; 2/8 didn't have
a statement.
Name of Australian company and 7/8
address
Telephone number 7/8
Emergency telephone number 3/8 The number given for these 3
(Australian number stating hours was the Australian Poisons
available) Line.
Identification
Product name 8/8
Recommended uses and methods of 7/8
application
Ingredients ?exact proportion or 7/8 One MSDS listed 3 separate
range formulations for 3 different
markets ?European, US,
Canadian without indicating
the Australian formulation.
Health Hazard Information
Damage to kidneys 3/8
Damage to liver 6/8
Damage to lung 8/8 Only MSDS for MMT
concentrates warned of risk of
acute pulmonary irritation as
well as chronic pulmonary
damage
CNS effects 8/8
Methylcyclopentadienyl manganese tricarbonyl (MMT) 123
First Aid Statements for ingestion, 8/8 One MSDS did not contain
inhalation, skin and eye exposure advice to contact a doctor
following eye exposure.
Precautions For Use
Personal Protective Equipment 8/8
Correct atmospheric exposure 7/8 Most MSDS refer to the
standard for MMT of 0.2 mg/m3 ACGIH standard for MMT
(TWA) (identical to that of NOHSC).
Skin notation explained 2/8 Skin notation was present in 7
MSDS but only 2 provided an
accompanying explanation.
Contact Point
Direct telephone number 7/8 Three of these 7 MSDS
containing a Contact Point
referred only to the Australian
Poisons Information Centre.
Priority Existing Chemical Assessment Report Number 24
124
Appendix 3 - Sample Material Safety Data
Sheet
for Methylcyclopentadienyl Manganese
Tricarbonyl (MMT)
MMT is classified as hazardous according to the National Occupational
Health and Safety Commission's Approved Criteria for Classifying
Hazardous Substances [NOHSC:1008(1994)].
Company Details
Company name
Address
State Postcode
Telephone number
Emergency telephone number
Identification
Product Name
Methylcyclopentadienyl manganese tricarbonyl
Other names
Manganese tricarbonyl [(1,2,3,4,5-)-1-methyl-2,4-cyclopentadien-1-
yl]-
MMT
Methylcymantrene
Manufacturer's product code
UN Number
2810 Toxic liquid, organic, nos
Dangerous goods class and subsidiary risk
Class 6.1 Packing Group I
Hazchem code
2X
Methylcyclopentadienyl manganese tricarbonyl (MMT) 125
Page of Total
2 5
Poisons Schedule Number
None allocated
Use
Physical description and properties
Appearance
Dark orange or yellow liquid
Boiling Point Freezing Point
231.7癈 2.2癈
Vapour pressure
0.01 kPa at 20癈
Specific Gravity
1.39 at 20癈
Flashpoint
96癈 (closed cup)
Flammability Limits
Lower: 0.3% at 153癈
Upper: 26% at 175癈
Solubility in water
0.029 g/L at 25癈
Other properties
Odour: herbaceous
Autoignition temperature: 257癈
Partition coefficient (log Pow): 3.4
Solubility: MMT is miscible in most hydrocarbon solvents.
Stability: MMT decomposes when exposed to light.
Polymerisation: MMT will not undergo hazardous polymerisation.
Ingredients/impurities
Chemical entitiy CAS Number Proportion
MMT 12108-13-3 100%
Impurities
Priority Existing Chemical
126
Page of Total
3 5
Health hazard information
HEALTH EFFECTS
Acute
Swallowed: Very toxic in animals by the oral route.
Eye: Slight eye irritant.
Skin: MMT is toxic in contact with skin and a slight skin
irritant. MMT penetrates the skin.
Inhaled: Very toxic in animals via inhalation.
Acute toxicity studies in rats, rabbits and mice have shown MMT to
induce damage to the lungs, kidney, liver and spleen effects,
tremors, convulsions, dyspnea and weakness.
In humans, the acute effects of MMT by skin or inhalation exposure
are reported to be burning of the skin, a metallic taste in the
mouth, "thick tongue", giddiness, headache, nausea, chest
tightness, gastrointestinal upset, laboured breathing and abnormal
sensation.
Chronic
Swallowed: In rats and mice, repeated oral exposure was associated
with weight loss and mild neurological and developmental effects.
Inhaled: In rats and mice, repeated exposure via inhalation was
associated with severe weight loss and death with degenerative
changes in the lungs, liver and kidney.
There are no human case reports or studies detailing symptoms
resulting from prolonged exposure to MMT. However, at chronic low
doses of MMT, neurological and psychological disturbances may
occur due to exposure to manganese.
FIRST AID
If swallowed, do NOT induce vomiting. Give a glass of water.
If in eyes, wash out immediately with water.
If skin contact occurs, remove contaminated clothing and wash skin
thoroughly.
Remove from contaminated area. Apply artificial respiration if not
breathing.
ADVICE TO DOCTOR
Treat symptomatically. No specific antidote. Aspiration of vomitis
can cause chemical pneumonitis which can be fatal.
Precautions for use
EXPOSURE STANDARD
Australian Exposure Standard (NOHSC) 0.2 mg/m3 8 hour TWA (as Mn)
with skin notation.
The "skin notation" (Sk) indicates that absorption through the
Methylcyclopentadienyl manganese tricarbonyl (MMT) 127
Page of Total
4 5
skin may be a significant source of exposure.
ENGINEERING CONTROLS
Use only with adequate ventilation. Local exhaust ventilation may
be necessary for some operations. Airborne concentrations should
be controlled to below the NOHSC exposure standard.
PERSONAL PROTECTION
Use suitable protective clothing to avoid skin contact. Chemical
resistant overalls (preferably disposable), neoprene, PVC or butyl
rubber gloves and boots, safety glasses or chemical goggles should
be used. If necessary, use a respirator with an organic vapour
cartridge to avoid breathing vapours in confined spaces or in
other places with limited ventilation.
Ensure good personal hygiene.
Fire fighting: wear self-contained breathing apparatus and
complete protective clothing.
Safe handling information
STORAGE AND TRANSPORT
Store in a cool dry place away from heat sources, ignition sources
and direct sunlight. Keep container closed.
Shipping Name: Metal Carbonyls NOS, Methylcyclopentadienyl
manganese tricarbonyl
Transport Label Required: Toxic liquid, organic, nos
Packing Group: 1
Initial Emergency Response Guide:
SPILLS AND DISPOSAL
Remove all sources of ignition. Use protective gloves to avoid
skin contact. Avoid breathing of vapours. Do not hose spills down
drains, sewers or waterways. Dyke and contain spilled material and
remove with inert absorbent. Store in closed container until
product can be properly disposed of. Contact local waste disposal
authority for advice or pass to a licensed waste disposal company
for disposal.
FIRE/EXPLOSION HAZARD
Keep containers tightly closed. Isolate from heat and flames. Use
self-contained breathing apparatus and complete protective
clothing. Use water fog or fine spray to extinguish.
Other information
TOXICOLOGICAL INFORMATION
Acute
Oral LD50 9?76 mg/kg bw (rat)
Dermal LD50 140-795 mg/kg bw (rat)
Inhalation LC50 220-247 mg/m3 bw (rat, 1 hour); >2-76 mg/m3 (rat,
4 hour)
Priority Existing Chemical
128
Page of Total
5 5
Repeat Dose
NOAEL (inhalation) 6.2 mg/m3 (rats and mice)
Environmental Data
MMT is subject to rapid photochemical degradation in the
atmosphere with a reported atmospheric half-life of 8-18 seconds.
MMT can adsorb to and become immobilised in soils reducing its
potential for photo-degradation.
Degradation of MMT in dark, anaerobic aqueous environments is
slow.
Aquatic Toxicity
MMT is toxic to aquatic organisms.
Daphnia Magna (4 and 48 hour EC50) 0.87 mg/L and 0.83 mg/L
respectively.
Bluegill sunfish TLm (LC50) (12 h) 0.2 mg/L.
Fathead Minnow TLm (LC50) (12 h) 0.23 - 0.36 mg/L.
Classification
R26 - Very Toxic by Inhalation
R28 ?Very Toxic if Swallowed
R24 ?Toxic in Contact with Skin
R48/23 ?Toxic: Danger of Serious Damage to Health by Prolonged
Exposure Through Inhalation
S36: Wear Suitable Protective Clothing
S38: In Case of Insufficient Ventilation Wear Suitable Respiratory
Equipment.
Further Information
National Industrial Chemicals Notification and Assessment Scheme
(NICNAS) Assessment Report on Methylcyclopentadienyl Manganese
Tricarbonyl: Priority Existing Chemical Assessment Report.
The full report can be downloaded from
http://www.nicnas.gov.au
Contact Point
Contact name Telephone number
Position title
Address
State Postcode Country
Methylcyclopentadienyl manganese tricarbonyl (MMT) 129
Appendix 4 ?Classification under the
Globally Harmonized System for Hazard
Classification and Communication
In this report, MMT has been classified against the NOHSC Approved Criteria for
Classifying Hazardous Substances (Approved Criteria) (NOHSC, 1999a) and, in the
case of physicochemical hazards, the Australian Dangerous Goods Code (ADG Code)
(FORS, 1998). However, classifications under the Globally Harmonized System for
Hazard Classification and Communication (GHS) (OECD 2002) will come into force
when the GHS is adopted by the Australian Government and promulgated into
Commonwealth legislation. GHS documentation is available at
http://www.unece.org/trans/danger/publi/ghs/officialtext.html
The classification of MMT against the GHS can be found below.
Health and Classification Hazard Communication
Environmental
Hazards
Acute toxicity Acute Toxicity Category 1 Symbol: Skull and Crossbones
Signal word: Danger
Hazard Statements:
Fatal if Swallowed
Fatal in Contact with Skin
Fatal if Inhaled
Symbol: New Health Hazard
Systemic toxicity- Repeated Exposure Category 1
Symbol
repeated exposure
Signal word: Danger
Hazard Statement: Causes
Damage to Organs Through
Prolonged or Repeated Exposure
by Inhalation.
Symbol: Fish and Tree
Ecotoxicity Category: Chronic 1
Signal word: Warning
Hazard Statement: Very Toxic
to Aquatic Life with Long-
Lasting Effects.
Priority Existing Chemical
130
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