Full Public Report format
File No: STD/1182
January 2006
NATIONAL INDUSTRIAL CHEMICALS NOTIFICATION AND ASSESSMENT SCHEME
(NICNAS)
FULL PUBLIC REPORT
C-FG-P
This Assessment has been compiled in accordance with the provisions of the Industrial Chemicals (Notification and
Assessment) Act 1989 (Cwlth) (the Act) and Regulations. This legislation is an Act of the Commonwealth of Australia.
The National Industrial Chemicals Notification and Assessment Scheme (NICNAS) is administered by the Department
of Health and Ageing, and conducts the risk assessment for public health and occupational health and safety. The
assessment of environmental risk is conducted by the Department of the Environment and Heritage.
For the purposes of subsection 78(1) of the Act, this Full Public Report may be inspected at:
Library
Australian Safety and Compensation Council
25 Constitution Avenue
CANBERRA ACT 2600
AUSTRALIA
To arrange an appointment contact the Librarian on TEL + 61 2 6279 1162 or email ascc.library@dewr.gov.au
This Full Public Report is available for viewing and downloading from the NICNAS website or available on request,
free of charge, by contacting NICNAS. For requests and enquiries please contact the NICNAS Administration
Coordinator at:
Street Address: 334 - 336 Illawarra Road MARRICKVILLE NSW 2204, AUSTRALIA.
Postal Address: GPO Box 58, SYDNEY NSW 2001, AUSTRALIA.
TEL: + 61 2 8577 8800
FAX + 61 2 8577 8888
Website: www.nicnas.gov.au
Director
NICNAS
TABLE OF CONTENTS
FULL PUBLIC REPORT....................................................................................................................................... 4
1. APPLICANT AND NOTIFICATION DETAILS ................................................................................... 4
2. IDENTITY OF CHEMICAL ................................................................................................................... 4
3. COMPOSITION ...................................................................................................................................... 4
4. INTRODUCTION AND USE INFORMATION..................................................................................... 5
5. PROCESS AND RELEASE INFORMATION ....................................................................................... 5
5.1. Distribution, transport and storage ................................................................................................. 5
5.2. Operation description...................................................................................................................... 5
5.3. Occupational exposure.................................................................................................................... 5
5.4. Release............................................................................................................................................ 6
5.5. Disposal .......................................................................................................................................... 6
5.6. Public exposure............................................................................................................................... 6
6. PHYSICAL AND CHEMICAL PROPERTIES ...................................................................................... 7
7. TOXICOLOGICAL INVESTIGATIONS ............................................................................................. 11
7.1. Acute toxicity ?oral ..................................................................................................................... 11
7.2. Acute toxicity ?dermal................................................................................................................. 11
7.3. Acute toxicity ?inhalation............................................................................................................ 12
7.4. Irritation ?skin ............................................................................................................................. 12
7.5. Irritation ?eye .............................................................................................................................. 13
7.7. Repeat dose toxicity...................................................................................................................... 13
7.8. Skin sensitisation ?mouse local lymph node assay (LLNA) ...................................................... 15
7.9. Genotoxicity ?bacteria................................................................................................................. 15
7.10. Genotoxicity ?in vitro (1) ............................................................................................................ 16
7.11. Genotoxicity ?in vitro (2) ............................................................................................................ 17
8. ENVIRONMENT .................................................................................................................................. 19
8.1. Environmental fate........................................................................................................................ 19
8.1.1. Ready biodegradability ............................................................................................................ 19
8.1.2. Bioaccumulation ...................................................................................................................... 20
8.2. Ecotoxicological investigations .................................................................................................... 20
8.2.1. Acute toxicity to fish (Rainbow trout) ..................................................................................... 20
8.2.1. Acute toxicity to fish (Orange-red killifish) ............................................................................ 21
8.2.2. Acute toxicity to aquatic invertebrates..................................................................................... 21
8.2.3. Algal growth inhibition test ..................................................................................................... 22
8.2.4. Inhibition of microbial activity ................................................................................................ 23
9. RISK ASSESSMENT ............................................................................................................................ 24
9.1. Environment ................................................................................................................................. 24
9.1.1. Environment ?exposure assessment........................................................................................ 24
9.1.2. Environment ?effects assessment ........................................................................................... 24
9.1.3. Environment ?risk characterisation ........................................................................................ 25
9.2. Human health................................................................................................................................ 25
9.2.1. Occupational health and safety ?exposure assessment ........................................................... 25
Office worker /Service technician.................................................................................................................... 25
9.2.2. Public health ?exposure assessment ....................................................................................... 25
9.2.3. Human health ?effects assessment.......................................................................................... 26
9.2.4. Occupational health and safety ?risk characterisation ............................................................ 26
9.2.5. Public health ?risk characterisation ........................................................................................ 26
10. CONCLUSIONS ?ASSESSMENT LEVEL OF CONCERN FOR THE ENVIRONMENT AND
HUMANS ........................................................................................................................................................ 27
10.1. Hazard classification..................................................................................................................... 27
10.2. Environmental risk assessment..................................................................................................... 27
10.3. Human health risk assessment ...................................................................................................... 27
10.3.1. Occupational health and safety ........................................................................................... 27
10.3.2. Public health........................................................................................................................ 27
11. MATERIAL SAFETY DATA SHEET............................................................................................. 27
11.1. Material Safety Data Sheet ........................................................................................................... 27
11.2. Label ............................................................................................................................................. 27
12. RECOMMENDATIONS .................................................................................................................. 28
Created on 13/12/2005 3:33 PM Last Saved 17/01/2006 10:46 AM
12.1. Secondary notification .................................................................................................................. 28
13. BIBLIOGRAPHY ............................................................................................................................. 29
January 2006 NICNAS
FULL PUBLIC REPORT
C-FG-P
1. APPLICANT AND NOTIFICATION DETAILS
APPLICANT(S)
Canon Australia Pty Ltd (ABN 66 005 002 951)
1 Thomas Holt Drive
North Ryde NSW 2113
NOTIFICATION CATEGORY
Standard: Chemical other than polymer (more than 1 tonne per year).
EXEMPT INFORMATION (SECTION 75 OF THE ACT)
Data items and details claimed exempt from publication:
Part B: 1(a) Chemical name, (d) CAS number, (e) Molecular formula, (e) Structural formula, (f)
Molecular weight, (g) Spectral data, 2(a) Purity, (c) Non-hazardous impurities
VARIATION OF DATA REQUIREMENTS (SECTION 24 OF THE ACT)
Variation to the schedule of data requirements is claimed as follows:
Part B: 7(a) Manufacturing process, 9(h) Dissociation constant, 9(j) Flash point, 9(n)
Reactivity
Part C: Acute Toxicity (c) Acute inhalation toxicity, Genetic Toxicity (h) Induction of germ
cell damage, Ecotoxicity (k) Daphnia sp., acute immobilisation/reproduction
PREVIOUS NOTIFICATION IN AUSTRALIA BY APPLICANT(S)
Low volume chemical permit, 2004
NOTIFICATION IN OTHER COUNTRIES
United Kingdom Annex VIIC notification, ref. 04-06-1759, July 2004
Annex VIIA notification, ref. 04-06-1759, August 2004
Switzerland October 2004
USA PMN No. P-04-0499, July 2004
Canada (Ontario) June 2004
Japan April 2005
Philippines Code No. SQ1-2004-032, November 2004
2. IDENTITY OF CHEMICAL
MARKETING NAME(S)
C-FG-P (preferred marketing name in Australia), C-FG, JPD YELLOW C-FG, JPD YELLOW C-FG
Liquid, Substituted stilbene sulfonic acid
3. COMPOSITION
DEGREE OF PURITY
>85%
HAZARDOUS IMPURITIES/RESIDUAL MONOMERS
None
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January 2006 NICNAS
ADDITIVES/ADJUVANTS
None
4. INTRODUCTION AND USE INFORMATION
MODE OF INTRODUCTION OF NOTIFIED CHEMICAL (100%) OVER NEXT 5 YEARS
The notified chemical will be imported into Australia as a component of inkjet printer ink. The ink is
contained within print cartridges, with volumes between 2 and 150 mL.
MAXIMUM INTRODUCTION VOLUME OF NOTIFIED CHEMICAL (100%) OVER NEXT 5 YEARS
Year 1 2 3 4 5
Tonnes <1 <1 <1 <1 <1
USE
The notified chemical is a dyestuff for inkjet printer ink, present in inks at 0.5-7%. The inks will be
used primarily by consumers and office workers.
5. PROCESS AND RELEASE INFORMATION
5.1. Distribution, transport and storage
PORT OF ENTRY
Sydney Airport or Sydney Harbour
IDENTITY OF MANUFACTURER/RECIPIENTS
The ink cartridges will be stored at the notifier's warehouse before their distribution to offices and
retailers of office supplies nationwide.
TRANSPORTATION AND PACKAGING
The notified chemical will be imported into Australia as a component of inks contained in ready-to-
use inkjet printer cartridges. There are a variety of different cartridges, within the following
dimensions:
?Physical size: 12 x 20 x 15 mm to 70 x 30 x 120 mm
?Volume: 2 mL to 150 mL
After import, the cartridges are transported by land and are stored in a warehouse under cool, dry
conditions, away from flames and sources of ignition. No safe transport or storage requirements apply
(not a hazardous or dangerous good).
5.2. Operation description
Sealed inkjet cartridges containing the notified chemical are manufactured in Japan, and are imported
intact. No reformulation, re-packaging, filling or re-filling of cartridges will take place within
Australia, as the inkjet printer cartridges are an end-use packaging.
End-users (general public, office workers or service technicians) will remove the inkjet cartridge from
its wrappings and use it to replace a spent cartridge in an inkjet printer as necessary. During the
printing process, the printer turns the ink into an extremely fine mist, which is transferred to paper or
other media in an automated fashion.
Used cartridges will primarily be disposed of to landfill or recycled.
5.3. Occupational exposure
Number and Category of Workers
Category of Worker Number Exposure Duration Exposure Frequency
(per day) (per year)
Importation/Dockside workers 50 < 8 hours 10-50 days
Storage and transport 15 < 8 hours 10-50 days
Office worker/consumer 2,000,000 10 seconds 2 days
Service technician 100 1 hour 170 days
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January 2006 NICNAS
Exposure Details
Dermal exposure is expected to be the main route of exposure. Inhalation exposure is unlikely, as the
notified chemical is of low volatility in a liquid preparation. Ocular exposure is also expected to be
unlikely, as the ink is only released in minute amounts within the confines of the printer.
Importation/dockside, storage and transport workers will only handle new, unopened cartridges
containing the notified chemical. Therefore, exposure is highly unlikely unless the packaging and
cartridges are accidentally breached.
The exposure of end-users of the inkjet printer cartridges (general public, office workers) is expected
to be limited to dermal exposure. This would occur only if the wet ink was inadvertently touched,
either while changing cartridges, from freshly printed media or if ink-stained parts of the printer were
touched. Instructions on how to replace the cartridge safely are included with the cartridge, and
reproduced on the inkjet printer. During the printing process, mist emission of the non-volatile
components of the ink from the printer is expected to be low. Once the ink dries, the notified chemical
would be trapped on the printed media, and therefore dermal exposure from contact with the dried ink
is not expected.
Service technicians may be exposed to the ink (containing up to 7% notified chemical) during repair
and cleaning of ink jet printers. Exposure is expected to be primarily dermal.
5.4. Release
RELEASE OF CHEMICAL AT SITE
No release of the notified chemical is expected, as no manufacturing or reformulation of the ink
containing the notified chemical will take place in Australia. Inkjet printer ink is imported in ready-to-
use cartridges of 2 to 150 mL (containing ink of <7% notified chemical). Environmental release of the
notified chemical is unlikely during importation, storage and transportation. In the event of a transport
accident, the individual container capacity, container and packaging specifications would limit the
extent of release to the environment.
RELEASE OF CHEMICAL FROM USE
Inkjet printer cartridges will be changed by office staff and the general public. Release of the ink
solution to the environment is not expected under normal use as the ink cartridges are designed to
prevent leakage. However, if leakage or spill does occur, the ink will be contained with absorbent
material, which will presumably be disposed of in landfill.
The majority of the notified chemical will undergo the same fate as the media on which it is printed.
Environmental release of the notified chemical is possible from media (although no release is
expected from printed paper) and from spent cartridges. Much of this will be disposed of to landfill.
Release is also possible during the recycling of both paper and cartridges. Recycling of treated paper
may result in the release of a proportion of the notified chemical to the aquatic compartment. The
notifier collects used, empty cartridges through collection boxes in general merchandising stores and
post offices etc., and a subcontractor disassembles and recycles them for raw materials. Any
remaining ink in these cartridges is washed out and disposed of through onsite wastewater treatment
plants before being released to the sewer. Around 5% (by weight) of ink will remain in the "empty"
cartridges, this results in a maximal release to the environment of 50 kg/year. Given that the use and
disposal of the ink across Australia will be dispersed, the overall concentration predicted to enter the
environment would be low.
5.5. Disposal
The import volume of the notified chemical will be disposed of primarily to landfill and through waste
produced by recycling processes. A large majority of the notified chemical will be disposed of as
normal office waste, ending up either in landfill or in paper recycling processes. The residual inks
remaining in "empty" cartridges accounts for the remainder of notified chemical (5%). While some of
this will be recycled, the majority will be disposed of to landfill.
5.6. Public exposure
Under normal usage, public exposure to the notified chemical will be negligible, because it is a minor
component of the printer ink (0.5-7%), and because it is contained within the cartridges. Generally
FULL PUBLIC REPORT: STD/1182 Page 6 of 30
January 2006 NICNAS
speaking, public exposure represents a smaller likelihood of exposure than workers. This is because
the main public users would be owners of home printers.
6. PHYSICAL AND CHEMICAL PROPERTIES
Appearance at 20oC and 101.3 kPa Orange powder (the imported ink is a yellow liquid)
>352癈
Melting Point/Freezing Point
OECD TG 102 Melting Point/Melting Range.
METHOD
EC Directive 92/69/EEC A.1 Melting/Freezing Temperature.
USA, EPA OPPTS Method 830.7200 Melting point/melting range
Remarks Test was performed using Differential Scanning Calorimetry. However, the
notified chemical decomposed from 352癈, forming black ash in a manner that
required atmospheric oxygen. Therefore, no melting point could be determined.
TEST FACILITY Safepharm Laboratories (2004a)
1597 kg/m3 at 20.5 ?0.5癈
Density
METHOD OECD TG 109 Density of Liquids and Solids.
EC Directive 92/69/EEC A.3 Relative Density.
USA, EPA OPPTS Method 830.7300: Density/relative density/bulk density.
Remarks Density was determined using a gas comparison pycnometer
TEST FACILITY Safepharm Laboratories (2004a)
<1.5 x 10-8 kPa at 25癈
Vapour Pressure
METHOD OECD TG 104 Vapour Pressure.
EC Directive 92/69/EEC A.4 Vapour Pressure.
USA, EPA OPPTS Method 830.7950: Vapour Pressure.
Remarks Method: Vapour Pressure Balance.
Readings at lower temperatures were too low and variable for an appropriate
statistical analysis. Instead, higher temperatures were analysed by regression, and
a value for 25癈 was extrapolated from the slope. A sequence of runs were started
after a sample of test material had been under vacuum for 5?h. Temperature and
pressure readings were taken between 190 and 250癈 with a one hour dwell at
240癈 between runs. The test material did not change in appearance under the
conditions used in the determination.
The test substance is classified as very slightly volatile (Mensink et al. 1995).
TEST FACILITY Safepharm Laboratories (2004b)
29.8-32.0% w/w of solution at 20癈
Water Solubility
OECD TG 105 Water Solubility.
METHOD
EC Directive 92/69/EEC A.6 Water Solubility.
USA, EPA OPPTS Method 830.7940: Water solubility: Column elution method;
shake flask method.
Remarks Flask Method ?Method variation: Due to high indeterminable saturation levels, it
was not possible to prepare samples at five times the saturation level as
recommended in the guidelines. Samples were prepared at different loading rates
to ensure that the result is a true reflection of water solubility.
A 32% (w/w) solution had some visible insoluble material present; a 29.8% (w/w)
solution did not. The pH of a saturated solution of the notified chemical was
measured to have a pH value of ~7.5.
TEST FACILITY Safepharm Laboratories (2004a)
72.6 ?0.5 mN/m at 21.5癈
Surface Tension
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January 2006 NICNAS
METHOD OECD TG 115 Surface Tension of Aqueous Solutions.
EC Directive 92/69/EEC A.5 Surface Tension.
Remarks A 1.03 g/L solution of the notified chemical was used, with an interfacial tension
balance.
The result was not corrected using the Harkins-Jordan correction table, as the
correction was not applicable to the apparatus used. This change was not
considered to have affected the integrity of the study.
The notified substance is not surface active.
TEST FACILITY Safepharm Laboratories (2004a)
Hydrolysis as a Function of pH
METHOD OECD TG 111 Hydrolysis as a Function of pH.
EC Directive 92/69/EEC C.7 Degradation: Abiotic Degradation: Hydrolysis as a
Function of pH.
USA, EPA OPPTS Method 835.2110: Hydrolysis as a function of pH
t?br>
pH T (癈)
4 25 > 1 year
7 25 > 1 year
9 25 > 1 year
After 120 hours (5 days) over the pH range and at 50oC it was found that less than
Remarks
10% of the test substance had hydrolysed, thus indicating a half-life of greater
than 1 year at 25癈.
The notified chemical is not likely to hydrolyse in the environment.
TEST FACILITY Safepharm Laboratories (2004a)
log10 Pow = -3.44 at 20癈
Partition Coefficient (n-octanol/water)
OECD TG 107 Partition Coefficient (n-octanol/water): Shake Flask Method.
METHOD
EC Directive 92/69/EEC A.8 Partition Coefficient.
USA, EPA OPPTS Method 830.7550: Partition Coefficient (n-octanol/water):
Shake Flask Method.
Remarks Flask Method: the concentration in the aqueous phase was determined by HPLC,
and that in the organic phase by spectrophotometry. The test was performed at
neutral pH, as is appropriate for salts like the notified chemical.
This result indicates that the notified chemical is likely to favour the water phase.
TEST FACILITY Safepharm Laboratories (2004a)
log10Koc < 1.25
Adsorption/Desorption
?screening test
OECD TG 121 Estimation of the Adsorption coefficient (Koc) on Soil and on
METHOD
Sewage Sludge using High Performance Liquid Chromatography (HPLC).
EC Directive 2001/59/EC C.19 Estimation of the Adsorption coefficient (Koc) on
Soil and on Sewage Sludge using High Performance Liquid Chromatography
(HPLC).
Remarks Column temperature was 40癈. The mobile phase was pH 7.0, so the test reflects
the ionised substance.
The HPLC screening method was used with 12 reference standards with known
adsorption coefficients. The retention time of the test substance was 1.63 minutes
which was less than that for acetanilide (4.001 minutes) which has a known log
Koc of 1.25, therefore the log adsorption coefficient is less than 1.25.
This result indicates that the notified chemical will be mobile in soils and
sediments.
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January 2006 NICNAS
TEST FACILITY Safepharm Laboratories (2004a)
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January 2006 NICNAS
pKa values are predicted to range between ?.07 and ?br>
Dissociation Constant
0.32.
A computer prediction of the pKa values was determined by the I-Lab Web
METHOD
Service v8.02.
Remarks This test was omitted, as the standard test methods are not applicable to substances
with multiple pKa values. The notified chemical contains multiple functional
groups with a variety of pKa values. The notified chemical has strong acid
functionalities, and will remain ionised throughout the environmental pH range of
4 to 9.
Particle Size
OECD TG 110 Particle Size Distribution/Fibre Length and Diameter
METHOD
Distributions.
Fraction Mass (%)
Range (m)
< 100 inhalable 21.9
< 10 respirable 4.11
Test was performed using a 100 m sieve and a cascade impactor for the smaller
Remarks
particle sizes. Too few particles were < 10 m to allow accurate assessment of
mass median aerodynamic diameter (MMAD).
TEST FACILITY Safepharm Laboratories (2004a)
Not highly flammable.
Flammability Limits
EC Directive 92/69/EEC A.10 Flammability (Solids).
METHOD
USA, EPA OPPTS Method 830.6315: Flammability.
Remarks The notified chemical failed to ignite during the screening test, so the main test
was not performed.
TEST FACILITY Safepharm Laboratories (2004c)
>400癈
Autoignition Temperature
EC Directive 92/69/EEC A.16 Relative Self-Ignition Temperature for Solids.
METHOD
Remarks The notified chemical did self-ignite, but only after the oven temperature had
reached 400癈.
TEST FACILITY Safepharm Laboratories (2004b)
Not explosive
Explosive Properties
EC Directive 92/69/EEC A.14 Explosive Properties.
METHOD
USA, EPA OPPTS Method 830.6316: Explodability
Remarks Not explosive on heating, friction or impact.
TEST FACILITY Safepharm Laboratories (2004b)
Not oxidising
Oxidising Properties
EC Directive 92/69/EEC A.17 Oxidising Properties (Solids).
METHOD
Remarks Predicted not to be oxidising on the basis of chemical structure.
Not expected to be reactive under normal environmental conditions.
Reactivity
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January 2006 NICNAS
7. TOXICOLOGICAL INVESTIGATIONS
Endpoint and Result Assessment Conclusion
Female rat, acute oral LD50 >2000 mg/kg bw low toxicity
Rat, acute dermal LD50 >2421 mg/kg bw low toxicity
Rabbit, skin irritation slightly irritating
Rabbit, eye irritation slightly irritating
Mouse Local Lymph Node Assay no evidence of sensitisation
Rat, repeat dose oral toxicity ?28 days. NOEL = 1000 mg/kg bw/day
Genotoxicity ?bacterial reverse mutation non mutagenic
Genotoxicity ?in vitro Mammalian Chromosome
non genotoxic
Aberration test (CHL cells)
7.1. Acute toxicity ?oral
TEST SUBSTANCE Notified chemical (82.6% pure)
OECD TG 423 Acute Oral Toxicity ?Acute Toxic Class Method.
METHOD
Species/Strain Female Rat/Sprague Dawley CD Strain
Vehicle Dimethylsulfoxide (10mL/kg)
Remarks - Method Dosage was adjusted to correspond to the relatively low purity of the test
substance (82.6%). Therefore, animals were dosed at higher levels to
account for the lower quantity of notified chemical in the test substance.
The dose recorded below describes the content of notified chemical
(2000 mg/kg bw) in the administered dose (2421 mg/kg bw). The dose
was administered by oral gavage.
RESULTS
Group Number and Sex Dose Mortality
of Animals mg/kg bw
1 3 females 2000 None
2 3 females 2000 None
LD50 >2000 mg/kg bw
Signs of Toxicity No signs of systemic toxicity were observed. All animals showed the
expected gains in bodyweight over the study period.
Effects in Organs No gross abnormalities were detected.
The notified chemical is of low toxicity via the oral route.
CONCLUSION
TEST FACILITY Safepharm Laboratories (2004d)
7.2. Acute toxicity ?dermal
TEST SUBSTANCE Notified chemical (82.6% pure)
OECD TG 402 Acute Dermal Toxicity.
METHOD
EC Directive 92/69/EEC B.3 Acute Toxicity (Dermal).
Species/Strain Rat/Sprague-Dawley CD strain
Vehicle Arachis oil BP was used to make the notified chemical into a paste.
Type of dressing Semi-occlusive.
Remarks - Method Dosage was adjusted to correspond to the relatively low purity of the test
substance (82.6%). Therefore, animals were dosed at higher levels to
account for the lower quantity of notified chemical in the test substance.
The dose recorded below describes the content of notified chemical
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January 2006 NICNAS
(2000 mg/kg bw) in the administered dose (2421 mg/kg bw). The dose
was administered to an area of skin (10% total body surface area), that
had been previously clipped of hair, and covered with a semi-occlusive
dressing for 24 hours.
RESULTS
Group Number and Sex Dose Mortality
of Animals mg/kg bw
1 5/sex 2000 None
LD50 >2000 mg/kg bw
Signs of Toxicity - Local No signs of dermal irritation were observed.
Signs of Toxicity - Systemic No signs of systemic toxicity were observed, and all animals showed the
expected gains in bodyweight over the study period.
Effects in Organs No abnormalities were observed at necropsy.
The notified chemical is of low toxicity via the dermal route.
CONCLUSION
TEST FACILITY Safepharm Laboratories (2004f)
7.3. Acute toxicity ?inhalation
No test for inhalation toxicity was performed. The dermal route was considered the more likely
route of exposure for the notified chemical, and hence this was chosen for the second acute
toxicity study.
7.4. Irritation ?skin
TEST SUBSTANCE Notified chemical (82.6% pure)
OECD TG 404 Acute Dermal Irritation/Corrosion.
METHOD
EC Directive 92/69/EEC B.4 Acute Toxicity (Skin Irritation).
Species/Strain Rabbit/New Zealand White
Number of Animals Three males
Vehicle 0.5 g notified chemical moistened with 0.5 mL water.
Observation Period 7 days
Type of Dressing Semi-occlusive.
Remarks - Method 4 hours of exposure to intact skin only. Animals were observed at 1, 24,
48 and 72 hours after exposure for evidence of primary irritation. An
additional observation was made at 7 days to assess the reversibility of
skin reactions.
RESULTS
Lesion Mean Score* Maximum Maximum Maximum Value at End
Animal No. Value Duration of Any of Observation Period
Effect
1 2 3
Erythema 1 0.33 1 1 7 days 0
Oedema 0 0 0 0 N/A N/A
*Calculated on the basis of the scores at 24, 48, and 72 hours for EACH animal.
Remarks - Results Slight orange-coloured staining was observed at all treated skin sites at 1
hour and 24 hours after exposure, but this did not affect observations. All
signs of erythema (slight) were fully reversible by seven days.
The notified chemical is slightly irritating to the skin.
CONCLUSION
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January 2006 NICNAS
TEST FACILITY Safepharm Laboratories (2004e)
7.5. Irritation ?eye
TEST SUBSTANCE Notified chemical (82.6% pure)
OECD TG 405 Acute Eye Irritation/Corrosion.
METHOD
EC Directive 92/69/EEC B.5 Acute Toxicity (Eye Irritation).
Species/Strain Rabbit/New Zealand White
Number of Animals Three males
Observation Period 7 days
Remarks - Method 75 mg of dry notified chemical was placed into the conjunctival sac of
the right eye only. An immediate pain assessment was performed, and
then animals were observed at 1, 24, 48 and 72 hours after exposure for
evidence of irritation. An additional observation was made at 7 days to
assess the reversibility of any irritation.
RESULTS
Lesion Mean Score* Maximum Maximum Maximum Value at End
Animal No. Value Duration of Any of Observation Period
Effect
1 2 3
Conjunctiva: redness 1.7 1 0.33 2 7 days 0
Conjunctiva: chemosis 0.7 0.7 0.3 2 < 3 days 0
Conjunctiva: discharge 0.7 1 0.3 2 < 3 days 0
Corneal opacity 0 0 0 0 N/A N/A
Iridial inflammation 0 0 0 0 N/A N/A
*Calculated on the basis of the scores at 24, 48, and 72 hours for EACH animal.
Remarks ?Results Initially, a single rabbit was used, but based on the results two more were
examined. All effects were fully reversible within 7 days.
Administration of the notified chemical to the rabbit's eyes caused slight
initial pain reactions in all animals.
Orange coloured staining of the fur around all treated eyes was observed
throughout the study. Yellow coloured staining of the nictitating
membrane was also observed, persisting until after 72 hours.
The notified chemical is slightly irritating to the eye
CONCLUSION
TEST FACILITY Safepharm Laboratories (2004g)
7.7. Repeat dose toxicity
TEST SUBSTANCE Notified chemical (96.5% pure)
OECD TG 407 Repeated Dose 28-day Oral Toxicity Study in Rodents.
METHOD
EC Directive 96/54/EC B.7 Repeated Dose (28 Days) Toxicity (Oral).
USA, EPA OPPTS Method 870.3050 Repeated 28-day oral toxicity study
in rodents
Rat/Sprague-Dawley Crl:CD?(SD) IGS BR
Species/Strain
Route of Administration Oral ?gavage
Exposure Information Total exposure days: 28 days
Dose regimen: 7 days per week
Post-exposure observation period: 14 days for two recovery groups.
Vehicle Distilled water
Remarks - Method No significant protocol deviations
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January 2006 NICNAS
RESULTS
Group Number and Sex Dose of notified Mortality
of Animals chemical
mg/kg bw/day
Control 5/sex 0 0
Control recovery 5/sex 0 0
Low dose 5/sex 25 0
Intermediate dose I 5/sex 150 0
Intermediate dose II 5/sex 300 0
High dose 5/sex 1000 0
High dose recovery 5/sex 1000 0
Mortality and Time to Death
No unscheduled deaths occurred during the study.
Clinical Observations
No clinically observable signs of toxicity were observed that could be related to treatment. Food/water
consumption and functional performance tests in the treated groups were all comparable with control groups.
Red/brown coloured faeces and bright yellow urine were observed from all animals treated with 1000 mg/kg
bw/day throughout the treatment period. This was associated with oral administration and subsequent
excretion of a coloured substance, and not indicative of toxicity.
A statistically significant reduction in body weight gain in the high dose recovery male group was considered
to be unrelated to treatment, as no reduction in body weight was observed in the high dose group.
Laboratory Findings ?Clinical Chemistry, Haematology, Urinalysis
No treatment-related, statistically significant effects were observed.
A statistically significant reduction in platelet count in the high dose recovery male group was considered to
be unrelated to treatment, as no reduction was observed in the high dose group. Similarly, some statistically
significant changes in blood chemistry results in both males and females of the high dose recovery group were
not observed in the high dose group, and were therefore thought to be of no toxicological importance.
Effects in Organs
No treatment-related effects in organ weight, macroscopic or microscopic abnormalities were detected.
Several statistically significant changes in organ weights were observed in various groups, but as similar
results were not observed in the high dose group these were not deemed to be of toxicological importance. In
the high dose recovery group, males were found to have reduced brain, liver and kidney weights, and females
had increased adrenal gland weight.
Remarks ?Results
While several statistically significant effects were observed in both males and females of the
high dose recovery group, these were not considered to be toxicologically relevant, due to the
absence of similar effects in the 28-day high dose group. Therefore, these results were not
considered in the determination of the NOEL, which was based on the absence of
toxicologically significant effects in the measured parameters at any dose in the study.
CONCLUSION
The No Observed Effect Level (NOEL) was established as 1000 mg/kg bw/day in this study, based on the lack
of toxicologically significant effects in the parameters measured.
From these test results, the notified chemical was therefore not classified as harmful.
TEST FACILITY Safepharm Laboratories (2004l)
FULL PUBLIC REPORT: STD/1182 Page 14 of 30
January 2006 NICNAS
7.8. Skin sensitisation ?mouse local lymph node assay (LLNA)
TEST SUBSTANCE Notified chemical (82.6% pure)
OECD TG 429 Skin Sensitisation ?Local Lymph Node Assay
METHOD
Species/Strain Mouse, CBA/Ca strain, female
Vehicle dimethylformamide
Number of Animals Test Group: 3 x 4 animals; Control Group: 1 x 4 animals
Remarks - Method 25 祃 of test solution (2.5%, 5.0% or 10% w/w in vehicle) was
administered to the dorsal surface of each ear for three consecutive days.
Dimethyl formamide was chosen as a vehicle because it allowed an
appropriate concentration to be applied during the assay.
Five days after topical application of the test material, the mice were
injected into the tail vein with 20 礐i of 3H- methyl thymidine. Five
hours later, the mice were killed by CO2 asphyxiation, and the lymph
nodes excised and pooled for each experimental group. The radioactivity
per lymph node was determined.
RESULTS
Concentration Proliferative response Stimulation Index*
(% w/w) (DPM/lymph node) (Test/Control Ratio)
Test Substance
0 (vehicle control) 670.92 N/A
2.5% 316.50 0.47
5.0% 588.67 0.88
10.0% 593.79 0.89
Positive Control -hexylcinnamaldehyde
5% Not supplied 1.76
10% Not supplied 2.78
25% Not supplied 5.06
* A Stimulation Index of >3.0 indicates a positive result
Remarks - Results No deaths or any signs of systemic toxicity were observed. Red/brown
staining of the ears was observed in all animals treated with 5% or 10%.
There was no evidence of induction of a lymphocyte proliferative
CONCLUSION
response indicative of skin sensitisation to the notified chemical.
TEST FACILITY Safepharm Laboratories (2004h)
7.9. Genotoxicity ?bacteria
Note: The Ames test was performed three times. Initially, an impure sample (C-FG) of the
notified chemical led to an aberrant positive result (Safepharm Laboratories (2004i)). Further
analysis of this sample discovered that the genotoxic component arose from a minor impurity
(Canon (2004c)). Further studies with a purified sample (C-FG-P) were found to be negative.
Presented here are the results for C-FG-P (Safepharm Laboratories (2004j)).
TEST SUBSTANCE Notified chemical (96.5% pure).
OECD TG 471 Bacterial Reverse Mutation Test.
METHOD
EC Directive 2000/32/EC B.13/14 Mutagenicity ?Reverse Mutation Test
using Bacteria.
Plate incorporation procedure.
Species/Strain S. typhimurium: TA1535, TA1537, TA98, TA100
E. coli: WP2uvrA
Metabolic Activation System Phenobarbitone/-naphthoflavone-induced S9 rat liver microsomes
FULL PUBLIC REPORT: STD/1182 Page 15 of 30
January 2006 NICNAS
Concentration Range in a) With metabolic activation: 50-5000 礸/plate
Main Test b) Without metabolic activation: 50-5000 礸/plate
Vehicle Distilled water
Remarks - Method A preliminary test was performed to determine the toxicity of the notified
chemical.
RESULTS
Metabolic Test Substance Concentration (礸/plate) Resulting in:
Cytotoxicity in Cytotoxicity in Precipitation Genotoxic Effect
Activation
Preliminary Test Main Test
Absent
Test 1 5000 (TA1535) >5000 Negative
Test 2 >5000 >5000 Negative
Present
Test 1 5000 (TA1535) >5000 Negative
Test 2 5000 (TA1537) >5000 Negative
Remarks - Results A yellow colour was noted staining the plates from 50 g/plate, but this
did not affect the scoring of the plates. The test chemical caused no
visible reduction in the bacterial background lawn at any dose level.
No significant increases in revertants were observed for the test chemical.
Positive controls verified both the assay and the S9 activation.
The notified chemical was not mutagenic to bacteria under the conditions
CONCLUSION
of the test.
TEST FACILITY Canon (2004a), Canon (2004c), Safepharm Laboratories (2004i),
Safepharm Laboratories (2004j)
7.10. Genotoxicity ?in vitro (1)
Note: Two in vitro chromosome aberration tests in Chinese Hamster Lung cells were performed.
Both indicated that the notified chemical was negative for genotoxicity. The second test is
presented below.
TEST SUBSTANCE Notified chemical (96.5% pure)
OECD TG 473 In vitro Mammalian Chromosome Aberration Test.
METHOD
Cell Type/Cell Line Chinese Hamster Lung (CHL or CHL/IU) cells
Metabolic Activation System Induced S9 rat liver microsomes
Vehicle Cell culture medium
Remarks - Method The concentrations of the notified chemical used in the preliminary cell
growth inhibition test were 19.54-5000 g/mL. No precipitation was
observed, so the maximum concentration was used in the main tests.
S9 were used at 5% final concentration in Test 1, and at 2% in Test 2.
Two replicate samples were performed for each data point.
Metabolic Test Substance Concentration (g/mL) Exposure Harvest
Time
Activation Period
Absent
Test 1 0*, 125, 250, 500, 1000*, 2000*, 4000* 6 hours 24
Test 2 0*, 39.07*, 78.13*, 156.25*, 234.38, 312.5, 625 24 hours 24
Present
Test 1 0*, 125, 250, 500, 1000*, 2000*, 4000* 6 hours 24
Test 2 0*, 312.5, 625, 1250*, 2500*, 3750, 5000* 6 hours 24
*Cultures selected for metaphase analysis.
FULL PUBLIC REPORT: STD/1182 Page 16 of 30
January 2006 NICNAS
RESULTS
Metabolic Test Substance Concentration (礸/mL) Resulting in:
Cytotoxicity in Cytotoxicity in Precipitation Genotoxic Effect
Activation
Preliminary Test Main Test
Absent
Test 1 >4000 g/mL >4000 g/mL Negative
Test 2 156.25 g/mL >625 g/mL Negative
Present
Test 1 >4000 g/mL >4000 g/mL Negative
Test 2 1250 g/mL* >5000 g/mL Negative
Remarks - Results * Dose related increases in mitotic index were observed in the with-S9
exposure group at doses above 1250 g/mL. These were considered to be
due to toxicity-induced cell-cycle synchronisation.
Positive control samples were included in each experiment. All of these
yielded their appropriate genotoxic responses, indicating that both the
system and the S9 microsomes were performing appropriately.
The notified chemical was not clastogenic to CHL cells treated in vitro
CONCLUSION
under the conditions of the test.
TEST FACILITY Safepharm Laboratories (2004k)
7.11. Genotoxicity ?in vitro (2)
TEST SUBSTANCE Notified Chemical (~100% pure)
Japanese test method (equivalent to OECD TG 473 In vitro Mammalian
METHOD
Chromosome Aberration Test).
Cell Type/Cell Line Chinese Hamster Lung (CHL) cells
Metabolic Activation System phenobarbital/5,6-benzoflavone-induced S9 rat liver microsomes
Vehicle Sterile physiological saline
Remarks - Method The concentrations of the notified chemical used in the preliminary cell
growth inhibition test were 39-5000 g/mL.
S9 were used at 5% final concentration.
Two replicate samples were performed for each data point.
Metabolic Test Substance Concentration Exposure Harvest
(g/mL) Time
Activation Period
Absent
Test 1a 39, 78, 156, 313, 625, 1250*, 2500*, 5000* 6 24
Test 1b 39, 78, 156*, 313*, 625*, 1250*, 2500, 5000 24 24
Test 1c 39, 78, 156*, 313*, 625*, 1250, 2500, 5000 48 48
Test 2a 1250*, 2500*, 5000* 6 24
Test 2b 156, 313*, 625*, 1250* 24 24
Test 2c 78, 156*, 313*, 625* 48 48
Present
Test 1 39, 78, 156, 313, 625, 1250*, 2500*, 5000* 6 24
Test 2 625, 1250*, 2500*, 5000* 6 24
*Cultures selected for metaphase analysis.
FULL PUBLIC REPORT: STD/1182 Page 17 of 30
January 2006 NICNAS
RESULTS
Metabolic Test Substance Concentration (礸/mL) Resulting in:
Cytotoxicity in Cytotoxicity in Precipitation Genotoxic Effect
Activation
Preliminary Test Main Test
Absent
Test 1a >5000 >5000 >5000
Test 1b 1250 625 >5000
Test 1c 625 625 >5000
Test 2a >5000 >5000 >5000
Test 2b 1250 >1250 >1250
Test 2c 625 >625 >625
Present
Test 1 >5000 >5000 >5000
Test 2 >5000 >5000 >5000
Remarks - Results Positive control samples were included in each experiment. All of these
yielded their appropriate genotoxic responses, indicating that both the
system and the S9 microsomes were performing appropriately.
The notified chemical was not clastogenic to CHL cells treated in vitro
CONCLUSION
under the conditions of the test.
TEST FACILITY Canon (2004b)
FULL PUBLIC REPORT: STD/1182 Page 18 of 30
January 2006 NICNAS
8. ENVIRONMENT
8.1. Environmental fate
8.1.1. Ready biodegradability
TEST SUBSTANCE Notified substance
OECD TG 301 C Ready Biodegradability: Modified MITI Test (I).
METHOD
Method of testing the biodegradability of chemical substances by
micro-organisms, in Testing methods for new chemicals substances,
July 13, 1974, No 5 Planning and Coordination Bureau, Environment
Agency.
Inoculum Activated sludge ?city plant
Exposure Period 28 days
Auxiliary Solvent
Analytical Monitoring BOD by Closed system oxygen consumption measurement ?soda lime.
TOC/DOC
HPLC
Remarks - Method Reference substance ?aniline
Concentration of suspended solids ?30 mg/L
Treatments:
- water + test substance ?100 mg/L ?vessel 1
- sludge + test substance ?100 mg/L ?vessel 2, 3 and 4
- sludge + aniline ?100 mg/L ?vessel 6
- control blank ?activated sludge only ?vessel 5
The temperature was measured daily (25oC). BOD was measured by data
sampler and autorecorder. At termination of study the dissolved organic
carbon, test substance concentration and pH were measured.
RESULTS
Test substance Aniline
Day % Degradation Day % Degradation
7 1 7 69
14 1 14 75
21 2 21 76
28 3 28 76
Percentage biodegradation via different methods ?ONLY in test solutions (Vessels 2, 3 & 4)
Method % degradation
Vessel 2 Vessel 3 Vessel 4 Average
BOD 4 3 3 3
TOC 5 5 5 5
HPLC 2 0 1 1
Remarks - Results All test validation criteria were met. The reference substance (aniline) degraded by
76% after 28 d confirming the suitability of the inoculum and test conditions.
Under the study conditions the test substance was not readily biodegradable.
CONCLUSION
TEST FACILITY Kurume Laboratory (2004a)
FULL PUBLIC REPORT: STD/1182 Page 19 of 30
January 2006 NICNAS
8.1.2. Bioaccumulation
TEST SUBSTANCE Notified Chemical
OECD TG 305C Bioconcentration: Flow-through Fish Test.
METHOD
EC Directive 98/73/EC C.13 Bioconcentration: Flow-Through Fish Test.
Method of testing the degree of accumulation of chemical substances in
fish bodies, in Testing methods for new chemicals substances, July
13 1974 (Revised October 8 1998), No 5 Planning and
Coordination Bureau, Environment Agency.
Species Carp (Cyprinus carpio)
Exposure Period Exposure: 28 days
Concentration Range 1.0 mg/L (Level 1)
0.1 mg/L (Level 2)
(Nominal)
Analytical Monitoring HPLC
Remarks - Method Continuous flow system. Test solutions were analysed once a week for a
total of 8 times. Treated fish were analysed after 2, 4, 6 and 8 weeks of
exposure (2 fish/analysis). There appears to have been no depuration
phase. No abnormality in behaviour or appearance of the test fish was
noted.
RESULTS
Bioconcentration Factor Level 1: 1.1
Level 2: 3.3
The results indicate that the notified chemical is not likely to
CONCLUSION
bioaccumulate.
TEST FACILITY Kurume Laboratory (2004b)
8.2. Ecotoxicological investigations
8.2.1. Acute toxicity to fish (Rainbow trout)
TEST SUBSTANCE Notified substance
OECD TG 203 Fish, Acute Toxicity Test ?semi-static conditions.
METHOD
EC Directive 92/69/EEC C.1 Acute Toxicity for Fish - semi-static
conditions.
Species Rainbow trout (Oncorhynchus mykiss)
Exposure Period 96 hours
Auxiliary Solvent None
100 mg CaCO3/L
Water Hardness
Analytical Monitoring Spectrophotometry
Remarks ?Method Based on range-finding tests it was determined that a limit test at
100 mg/L would be done. A measured amount of test substance was
dissolved in water. The concentration and stability of the test solution
was determined at 0, 24 and 96 hours.
The test vessels, each with 10 fish, were covered, maintained at 14oC,
exposed to a photoperiod of 16 dark/8 hours light and were aerated
throughout the study. Temperature, pH and dissolved oxygen were
recorded daily. Test solution was renewed daily. Observations were made
at 3, 6, 24, 48, 72 and 96 hours with the fish being transferred to clean
water for the observations.
FULL PUBLIC REPORT: STD/1182 Page 20 of 30
January 2006 NICNAS
RESULTS
Concentration mg/L Number of Fish Mortality
Nominal Actual 6h 24 h 48 h 72 h 96 h
0 - 20 0 0 0 0 0
93%*
100 20 0 0 0 0 0
*mean measurement of two analyses of freshly prepared solutions.
LC50 >100 mg/L nominal at 96 hours.
NOEC 100 mg/L nominal at 96 hours.
Remarks ?Results No sublethal effects were observed in the fish throughout the study. All
environmental parameters stayed within acceptable ranges.
Under the study conditions the test substance is very slightly toxic to fish
CONCLUSION
(Mensink et al. 1995).
TEST FACILITY SafePharm Laboratories (2004m)
8.2.1. Acute toxicity to fish (Orange-red killifish)
TEST SUBSTANCE Notified Chemical
Japanese Industrial Standard (JIS K 0102-1998-71.), "Testing Methods for
METHOD
industrial waste water, Acute toxicity test with fish".
Species Orange璻ed killifish (Oryzias laptipes)
Exposure Period 96 h
Auxiliary Solvent None
Water quality parameters of pH, water temperature, and O2 content
Remarks ?Method
remained within normal limits throughout the study.
RESULTS
Concentration mg/L Number of Fish Mortality
Nominal Actual 24 h 48 h 72 h 96 h
0 - 10 0 0 0 0
250 10 0 0 0 0
500 10 0 0 0 1
1000 10 0 1 4 5
LC50 1000 mg/L at 96 hours.
NOEC 250 mg/L at 96 hours.
Remarks ?Results This was preliminary to the bioaccumulation test.
Under the study conditions the test substance is very slightly toxic to fish
CONCLUSION
(Mensink et al. 1995).
TEST FACILITY Kurume Laboratory (2004b)
8.2.2. Acute toxicity to aquatic invertebrates
TEST SUBSTANCE Notified Substance
OECD TG 202 Daphnia sp. Acute Immobilisation Test ?static
METHOD
conditions.
EC Directive 92/69/EEC C.2 Acute Toxicity for Daphnia - static
conditions.
Species Daphnia magna
Exposure Period 48 hours
FULL PUBLIC REPORT: STD/1182 Page 21 of 30
January 2006 NICNAS
Auxiliary Solvent None
250 mg CaCO3/L
Water Hardness
Analytical Monitoring Spectrophotometry
Remarks - Method Based on range-finding tests it was determined that a limit test at
100 mg/L would be done. The concentration and stability were verified
by analysis at 0 and 48 hours. The solutions were clear throughout the
study.
The test vessels (4 replicates), each with 10 daphnia, were covered,
maintained at 21oC, exposed to a photoperiod of 16 dark/8 hours light
and were not aerated throughout the study. Temperature was recorded
daily, while pH and dissolved oxygen were recorded at the start and end
of the study. Observations were made at 24 and 48 hours. Two controls
were done in parallel.
RESULTS
Concentration mg/L Number of D. magna Number Immobilised
Nominal Actual 24 h 48 h
0 - 20 0 0
98%*
100 40 0 0
*mean measurement of two analyses of freshly prepared solutions.
LC50 >100 mg/L nominal at 48 hours
NOEC 100 mg/L nominal at 48 hours
Remarks - Results No sublethal effects were observed in the daphnia throughout the study.
All environmental parameters stayed within acceptable ranges.
Under the study conditions the test substance is very slightly toxic to
CONCLUSION
aquatic invertebrates (Mensink et al. 1995).
TEST FACILITY SafePharm Laboratories (2004n)
8.2.3. Algal growth inhibition test
TEST SUBSTANCE Notified substance
OECD TG 201 Alga, Growth Inhibition Test.
METHOD
EC Directive 92/69/EEC C.3 Algal Inhibition Test.
Species Scenedesmus subspicatus
Exposure Period 72 hours
Concentration Range Nominal: 3.2, 10, 32, 100 and 320 mg/L
Actual: 3.06, 10.1, 32, 101 and 321 mg/L at time 0 hours
Actual: 3.06, 10.2, 32.6, 104 and 330 mg/L at time 72 hours
Auxiliary Solvent None
Water Hardness Not specified
Analytical Monitoring Spectrophotometry
Remarks - Method Two experimental methods were conducted in parallel to differentiate if
the growth effects were due to toxicity or light intensity. Both used the
same test concentrations and a cell density of 1.0 ?1.4 ?104 cells/mL.
Constant illumination and stirring, and temperature maintained at 24 ?br>
1癈.
Experiment A: 3 replicates per concentration and 3 controls. Algae were
exposed to test material in a flask enclosed from above by a petri dish
containing culture medium only. Inhibition was due to a combination of
toxicity and reduction in light intensity. The test solutions increased in
yellow colour to bright orange intensity with increasing concentration.
Experiment B: 3 replicates per concentration and 3 controls. Algae were
not exposed to the test material in the flasks, but the flasks were enclosed
FULL PUBLIC REPORT: STD/1182 Page 22 of 30
January 2006 NICNAS
by petri dishes containing the culture media and the test material.
Therefore, inhibition of algal growth was due to a reduction in light
intensity alone.
Test solutions from experiment A at 0 and 72 hours were analysed to
confirm concentration. It was found that the test concentrations ranged
from 96 to 104% of the nominal concentration. Hence, nominal
concentrations were used in analysis.
RESULTS
Experiment A: Growth Experiment B: Growth
EbC50 ErC50 NOEC EbC50 ErC50 NOEC
mg/L at 72 h mg/L at 72 h mg/L mg/L at 72 h mg/L at 72 h mg/L
110 >320 3.2 34 >320 3.2
Remarks - Results In experiment A, both the growth and biomass were affected by the
presence of the test substance.
In experiment B, both the growth and biomass were affected by the
reduction in light due to the presence of the test substance in the Petri
dish.
In both experiments the cell concentration in the controls increased by a
factor greater than 16 after 72 hours, which meets the validity criteria.
Since the inhibition of growth was similar in both Experiment A and
Experiment B the growth inhibition is attributable to the reduction of
light intensity due to the highly coloured nature of the test material rather
than intrinsic toxic properties of the test material.
Under the study conditions, the test substance is very slightly toxic to
CONCLUSION
algae (Mensink et al. 1995)
TEST FACILITY SafePharm Laboratories (2004o)
8.2.4. Inhibition of microbial activity
TEST SUBSTANCE Notified Substance
OECD TG 209 Activated Sludge, Respiration Inhibition Test.
METHOD
EC Directive 88/302/EEC C.11 Biodegradation: Activated Sludge
Respiration Inhibition Test
Inoculum Activated sewage sludge from a domestic STP
Exposure Period 3 hours
Concentration Range Nominal: 1000 mg/L
Remarks ?Method From a range finding test, it was determined that only one test
concentration needed to be used ?1000 mg/L. The study was conducted
in triplicate. Vessels were aerated during the tests, and O2 consumption
rates were monitored. Temperature was maintained at 21癈. Duplicate
controls were run in parallel. The rate of respiration was determined after
30 minutes and 3 hours contact.
Reference substance ?3,5-dichlorophenol.
Total water hardness ?100 mg/L CaCO3.
RESULTS
EC50 >1000 mg/L
NOEC 1000 mg/L
Reference substance 3 h EC50 = 12 mg/L
Remarks ?Results
FULL PUBLIC REPORT: STD/1182 Page 23 of 30
January 2006 NICNAS
The validity criteria for control respiration rates variation and reference
material toxicity were satisfied. Environmental parameters were within
acceptable ranges.
Under the study conditions the test substance is not toxic to micro-
CONCLUSION
organisms.
TEST FACILITY SafePharm Laboratories (2004p)
9. RISK ASSESSMENT
9.1. Environment
9.1.1. Environment ?exposure assessment
The environmental safety controls and use pattern for the notified chemical would indicate a
limited potential for its release into the environment.
The notified chemical is readily soluble in water; however, aquatic release during use is
considered unlikely and after drying the notified chemical is likely to be stable within an inert
matrix on printed paper products. Waste paper may be disposed of directly to landfill with the
notified chemical strongly bound to the paper. It is anticipated that prolonged residence in an
active landfill environment would eventually degrade the compound. Incineration of waste
paper will destroy the compound with the generation of water vapour and oxides of carbon,
nitrogen and sulphur plus sodium salts.
Emptied ink cartridges containing a residue of notified chemical may be recycled or be sent to
landfill for disposal. During recycling the cartridges will be dismantled and the notified
chemical will be washed off, ultimately finding its way into onsite treatment works prior to
discharge into the sewer. As a worst case, this would account for 50 kg of the notified chemical
being discharged to sewer, assuming all cartridges were recycled and no removal occurs in
onsite treatment works. In a landfill, the notified chemical is expected to be immobile, and
eventually it will degrade through biotic and abiotic processes, and consequently, should not
pose a significant exposure hazard to the environment.
Approximately 50% of the printed paper will enter the recycling process. During the recycling
process, waste paper is repulped using a variety of alkaline, dispersing and wetting agents,
water emulsifiable organic solvents and bleaches. These agents enhance fibre separation, toner
detachment from the fibres, pulp brightness and the whiteness of the paper. Due to its high
solubility, a predicted environmental concentration (PEC) can be estimated assuming 50% of
the total imported notified chemical enters recycling, of which 50% (ie 25% of imported
volume) will remain in the supernatant effluent discharged to sewer (assuming no WWTP
attenuation). Based on the releases to sewer from the recycling of cartridges and printed paper.
The predicted environmental concentration (PEC) of the notified chemical would be:
Amount in effluent entering sewer 900 kg
Number of days 365
National population 20.1 million
Litres per person 200 L
0.60 礸/L.
PECsewer
A bioaccumulation study with carp found bioconcentration factors between 3.0 times
indicating that the chemical is not likely to bioaccumulate.
9.1.2. Environment ?effects assessment
The results of the ecotoxicological data indicate the notified chemical is harmful to algae, very
slightly toxic to fish and daphnia and not toxic to microorganisms. The most sensitive species
are algae, where the EbC50 of 34 mg/L. Acute results are available for 3 trophic levels, so it is
applicable to apply an assessment factor of 100 to the most sensitive species (algae), thus the
predicted no effect concentration (PNEC) is 340 礸/L.
FULL PUBLIC REPORT: STD/1182 Page 24 of 30
January 2006 NICNAS
9.1.3. Environment ?risk characterisation
A worst-case calculation indicates a PEC/PNEC ratio of >>0.01 (0.60/340) for aquatic
ecosystems via sewer discharge, indicating a low environmental risk.
The notified chemical is not likely to present a risk to the environment when it is stored,
transported, used, recycled and disposed of in the proposed manner.
9.2. Human health
9.2.1. Occupational health and safety ?exposure assessment
Importation/Dockside/Storage and transport workers
As the notified chemical will be imported in pre-packed, sealed cartridges, workers are unlikely
to be exposed to the notified chemical except in the unlikely event of accidental rupture during
transport and storage.
Office worker /Service technician
Workers may be exposed to the notified chemical through dermal contact while changing spent
cartridges, repairing printers or during normal printing processes. Due to the notified chemical
being contained within sealed cartridges, dermal exposure would only occur occasionally and in
minute quantities. In addition, workers would avoid exposure with wet inks because it would
stain the skin and/or smudge an undried printed page. Some intermittent exposure may occur
when printing onto non-absorbent media when the ink has not yet dried. After drying, exposure
to the notified chemical on paper printed with ink containing the notified chemical is low as the
dye is bound to the paper matrix.
Service technicians are expected to have the highest occupational exposure, but this will be
minimised by their use of disposable gloves.
In the unlikely situation where the entire palms of a worker's hands are covered with ink
containing a maximum of 7% notified chemical, exposure could be estimated as follows:
Exposure to
Thickness of Frequency
Concentration of
Contact Dermal notified
notified chemical Product Layer of
Area Absorption
Product chemical
in product on Skin occurrence
(cm2)b b
(%) (mg/kg
(mg/cm3)a (cm)b (per day)c
bw/day)d
Ink 70 420 0.01 10 1 0.42
a
assuming ink has a specific gravity of 1.
b
data from European Chemical Bureau Technical Guidance Document on Risk Assessment
(European Commission, 2003).
c
no frequency data is available. The occurrence of this scenario once per day is considered
to be reasonable worst-case.
d
assuming 70kg body weight
Ocular, oral and inhalation exposure are not expected to occur during normal use.
9.2.2. Public health ?exposure assessment
As consumers, the public may be intermittently exposed to the notified chemical in a similar
fashion to office workers ?when replacing spent cartridges and from undried printed media.
However, the consumers are less likely to use the printer as often as workers, and therefore
their potential exposure is expected to be lower. Accidental dermal exposure to ink containing
the notified chemical would also be avoided because of skin staining and/or smudging of
undried printed media.
Ocular, oral and inhalation exposure are not expected to occur during normal use.
Overall, exposure of the public is expected to be low, due to the small quantity of notified
chemical in each cartridge, the sealed design of cartridges, the automated release during
printing, and intermittent nature of exposure.
FULL PUBLIC REPORT: STD/1182 Page 25 of 30
January 2006 NICNAS
9.2.3. Human health ?effects assessment
Toxicokinetics, metabolism and distribution
In the Repeated Dose 28-day Oral Toxicity Study in rats, urine and faeces were observed to
coloured, indicating that the notified chemical and/or its coloured metabolites are excreted via
these routes. Additionally, colouration of urine indicates that the notified chemical is absorbed
from the gastrointestinal tract.
Absorption of the notified chemical through the skin is expected to be very low, due to the high
molecular weight of the notified chemical and its low log Pow. This is supported by the lack of
acute dermal toxicity observed.
Acute toxicity
The notified chemical is considered to be of low acute toxicity when administered orally or
when applied to the skin. Inhalation toxicity has not been determined, however, exposure to the
notified chemical through inhalation is unlikely.
Irritation and Sensitisation
Rabbit studies of eye and skin irritation found that the notified chemical is slightly irritating to
both skin and eyes. The notified chemical caused staining of the skin for up to 24 hours, and
erythema persisted up to 3 days. The notified chemical also caused staining of the nictitating
membrane of the eye, which also persisted for up to 3 days. All effects were fully reversible by 7
days after exposure.
The notified chemical is not considered to be a sensitiser, based on the mouse local lymph node
assay results.
Repeated Dose Toxicity
The 28-day repeat dose oral toxicity study in rats showed that the notified chemical did not
cause any adverse reactions that could be associated with its administration. Based on this, a No
Observable Effect Level (NOEL) was established as 1000 mg/kg bw/day. It is therefore
considered to be of low toxicity.
Mutagenicity
The notified chemical was found to be non-mutagenic in two independent Ames tests and non-
clastogenic in two independent in vitro chromosomal aberration tests in cultured CHL cells. It is
therefore not considered to be genotoxic in vitro.
Based on the available data, the notified chemical is not classified as a hazardous substance in
accordance with the NOHSC Approved Criteria for Classifying Hazardous Substances (NOHSC
2004).
9.2.4. Occupational health and safety ?risk characterisation
The notified chemical is a minor component of printer inks (0.5-7%). Dermal exposure to ink is
unlikely when cartridges are handled carefully, and it should only occur sporadically. In the
event of dermal exposure, toxicity is unlikely as any potential exposure is expected to occur in
only small quantities, and because the notified chemical is not classified as hazardous. If the
likelihood of exposure to ink in greater quantities or with greater frequency is likely, then the
appropriate PPE should be worn to reduce any potential risk (eg, gloves for inkjet printer
service technicians). Ocular, oral or inhalation exposure to the notified chemical should not
occur during normal use.
9.2.5. Public health ?risk characterisation
The notified chemical is a minor component of printer inks (0.5-7%). Dermal exposure to ink is
unlikely when cartridges are handled carefully, and it should only occur sporadically. In the
event of dermal exposure, toxicity is unlikely as any potential exposure is expected to occur in
only small quantities, and because the notified chemical is relatively non-toxic. Ocular, oral or
inhalation exposure to the notified chemical should not occur during normal use.
FULL PUBLIC REPORT: STD/1182 Page 26 of 30
January 2006 NICNAS
10. CONCLUSIONS ?ASSESSMENT LEVEL OF CONCERN FOR THE ENVIRONMENT AND
HUMANS
10.1. Hazard classification
Based on the available data the notified chemical is not classified as hazardous under the
NOHSC Approved Criteria for Classifying Hazardous Substances.
and
As a comparison only, the classification of the notified chemical using the Globally Harmonised
System for the Classification and Labelling of Chemicals (GHS) (United Nations 2003) is
presented below. This system is not mandated in Australia and carries no legal status but is
presented for information purposes. On environmental grounds the notified substance would
have the classification of Chronic 3.
Based on the available data, the notified chemical does not meet the criteria for the
Classification and Labelling of Chemicals according to the United Nations (2003) Globally
Harmonised System.
10.2. Environmental risk assessment
On the basis of the PEC/PNEC ratio the chemical is not considered to pose a risk to the
environment based on its reported use pattern.
10.3. Human health risk assessment
10.3.1. Occupational health and safety
There is Low Concern to occupational health and safety under the conditions of the
occupational settings described.
10.3.2. Public health
There is No Significant Concern to public health when the notified chemical is used as a
component of pre-packed inkjet printer inks.
11. MATERIAL SAFETY DATA SHEET
11.1. Material Safety Data Sheet
The MSDS of the product containing the notified chemical provided by the notifier was were in
accordance with the NOHSC National Code of Practice for the Preparation of Material Safety
Data Sheets (NOHSC, 2003). It is published here as a matter of public record. The accuracy of
the information on the MSDS remains the responsibility of the applicant.
11.2. Label
The label for the product containing the notified chemical provided by the notifier was in
accordance with the NOHSC National Code of Practice for the Labelling of Workplace
Substances (NOHSC, 1994). The accuracy of the information on the label remains the
responsibility of the applicant.
FULL PUBLIC REPORT: STD/1182 Page 27 of 30
January 2006 NICNAS
12. RECOMMENDATIONS
CONTROL MEASURES
Occupational Health and Safety
? Service personnel should wear cotton or disposable gloves and ensure adequate
ventilation is present when removing spent printer cartridges containing the notified
chemical and during routine maintenance and repairs.
? A copy of the MSDS should be easily accessible to employees.
? If products and mixtures containing the notified chemical are classified as hazardous to
health in accordance with the NOHSC Approved Criteria for Classifying Hazardous
Substances, workplace practices and control procedures consistent with provisions of
State and Territory hazardous substances legislation must be in operation.
Disposal
? The notified chemical should be disposed of by incineration or to landfill in accordance
with State/Territory waste disposal regulations. Paper products impregnated with ink
containing the notified chemical may be incinerated, recycled or landfilled.
Emergency procedures
? Spills/release of the notified chemical should be handled by soaking up spilled ink with
absorbent material.
12.1. Secondary notification
The Director of Chemicals Notification and Assessment must be notified in writing within 28
days by the notifier, other importer or manufacturer:
(1) Under Section 64(2) of the Act:
- if any of the circumstances listed in the subsection arise.
The Director will then decide whether secondary notification is required.
No additional secondary notification conditions are stipulated.
FULL PUBLIC REPORT: STD/1182 Page 28 of 30
January 2006 NICNAS
13. BIBLIOGRAPHY
Canon (2004a) Report of Mutagenicity Test using Microorganisms (Report no. 694, 5 February 2004). Tokyo,
Japan, Canon Inc, (unpublished report provided by notifier).
Canon (2004b) C-FG: Metaphase Analysis in CHL Cells in vitro (Report no. C053, 09 February 2004). Tokyo,
Japan, Canon Inc, (unpublished report provided by notifier).
Canon (2004c) Report on the Cause of Ames test Positive for CF-G by Mr H. Takai (10 March 2004). Tokyo,
Japan, Canon Inc, (unpublished report provided by notifier).
European Commission (2003) Technical Guidance Document on Risk Assessment in Support of Commission
Directive 93/67/EEC on Risk Assessment for New Notified Substances and Commission Regulation (EC)
1488/94 on Risk Assessment for Existing Substances and Directive 98/8/EC of the European Parliament and
of the Council Concerning the Placing of Biocidal Products on the Market ?Part I. Institute for Health and
Consumer protection, European Chemicals Bureau, European Communities.
Kurume Laboratory (2004a) Biodegradation study of C-FG by microorganisms (Study number 14167, 24 March
2004). Japan, Kurume Laboratory Chemicals Evaluation and Research Institute. Sponsor: Nippon Kayaku
Co. Ltd, (unpublished report provided by the notifier).
Kurume Laboratory (2004b) Bioconcentration study of C-FG in carp (Study number 44168, 21 April 2004).
Japan, Kurume Laboratory Chemicals Evaluation and Research Institute. Sponsor: Nippon Kayaku Co Ltd,
(unpublished report provided by the notifier).
Mensink BJWG, Montforts M, Wijkhuizen-Maslankiewicz L, Tibosch H and Linders JBHJ (1995). Manual for
summarising and evaluating the environmental aspects of pesticides. National Institute of Public Health and
Environmental Protection, Bilthoven, The Netherlands.
NOHSC (1994) National Code of Practice for the Labelling of Workplace Substances [NOHSC:2012(1994)].
National Occupational Health and Safety Commission, Canberra, Australian Government Publishing
Service.
NOHSC (2004) Approved Criteria for Classifying Hazardous Substances [NOHSC:1008(2004)]. National
Occupational Health and Safety Commission, Canberra, AusInfo.
NOHSC (2003) National Code of Practice for the Preparation of Material Safety Data Sheets, 2nd edn
[NOHSC:2011(2003)]. National Occupational Health and Safety Commission, Canberra, Australian
Government Publishing Service.
Safepharm Laboratories (2004a) C-FG: Determination of General Physico-chemical Properties (Project No.
345/732, 31 March 2004) Safepharm Laboratories Ltd, Shardlow, UK. Sponsor: Canon Inc, Japan
(unpublished report provided by notifier).
Safepharm Laboratories (2004b) C-FG: Determination of Hazardous Physico-chemical Properties (Project No.
345/733, 12 July 2004) Safepharm Laboratories Ltd, Shardlow, UK. Sponsor: Canon Inc, Japan
(unpublished report provided by notifier).
Safepharm Laboratories (2004c) C-FG: Determination of Flammability (Solids) (Project No. 345/734, 24
February 2004) Safepharm Laboratories Ltd, Shardlow, UK. Sponsor: Canon Inc, Japan (unpublished report
provided by notifier).
Safepharm Laboratories (2004d) C-FG: Acute Oral Toxicity in the Rat ?Acute Toxic Class Method (Project No.
345/735, 02 April 2004) Safepharm Laboratories Ltd, Shardlow, UK. Sponsor: Canon Inc, Japan
(unpublished report provided by notifier).
Safepharm Laboratories (2004e) C-FG: Acute Dermal Irritation in the Rabbit (Project No. 345/737, 02 April
2004) Safepharm Laboratories Ltd, Shardlow, UK. Sponsor: Canon Inc, Japan (unpublished report provided
by notifier).
Safepharm Laboratories (2004f) C-FG: Acute Dermal Toxicity (Limit Test) in the Rat (Project No. 345/736, 02
April 2004) Safepharm Laboratories Ltd, Shardlow, UK. Sponsor: Canon Inc, Japan (unpublished report
provided by notifier).
Safepharm Laboratories (2004g) C-FG: Acute Eye Irritation in the Rabbit (Project No. 345/738, 29 July 2004)
Safepharm Laboratories Ltd, Shardlow, UK. Sponsor: Canon Inc, Japan (unpublished report provided by
notifier).
FULL PUBLIC REPORT: STD/1182 Page 29 of 30
January 2006 NICNAS
Safepharm Laboratories (2004h) C-FG: Local Lymph Node Assay in the Mouse (Project No. 345/739, 02 April
2004) Safepharm Laboratories Ltd, Shardlow, UK. Sponsor: Canon Inc, Japan (unpublished report provided
by notifier).
Safepharm Laboratories (2004i) C-FG: Reverse Mutation Assay "Ames Test" using Salmonella typhimurium
and Escherichia coli (Project No. 345/742, 05 April 2004) Safepharm Laboratories Ltd, Shardlow, UK.
Sponsor: Canon Inc, Japan (unpublished report provided by notifier).
Safepharm Laboratories (2004j) C-FG: Reverse Mutation Assay "Ames Test" using Salmonella typhimurium
and Escherichia coli (Project No. 345/752, 19 May 2004) Safepharm Laboratories Ltd, Shardlow, UK.
Sponsor: Canon Inc, Japan (unpublished report provided by notifier).
Safepharm Laboratories (2004k) C-FG: Chromosome Aberration Test in CHL Cells in vitro (Project No.
345/751, 01 November 2004) Safepharm Laboratories Ltd, Shardlow, UK. Sponsor: Canon Inc, Japan
(unpublished report provided by notifier).
Safepharm Laboratories (2004l) C-FG-P: Twenty-eight Day Repeated Dose Oral (Gavage) Toxicity Study in the
Rat (Project No. 345/750, 18 October 2004) Safepharm Laboratories Ltd, Shardlow, UK. Sponsor: Canon
Inc, Japan (unpublished report provided by notifier).
Safepharm Laboratories (2004m) C-FG-P: Acute Toxicity to Rainbow Trout (Oncorhynchus mykiss) (Project
No. 345/753, 05 July 2004) Safepharm Laboratories Ltd, Shardlow, UK. Sponsor: Canon Inc, Japan
(unpublished report provided by notifier).
Safepharm Laboratories (2004n) C-FG-P: Acute Toxicity to Daphnia magna (Project No. 345/754, 05 July
2004) Safepharm Laboratories Ltd, Shardlow, UK. Sponsor: Canon Inc, Japan (unpublished report provided
by notifier).
Safepharm Laboratories (2004o) C-FG-P: Inhibition of Algal Growth Caused by Coloured Test Substances
(Project No. 345/755, 30 July 2004) Safepharm Laboratories Ltd, Shardlow, UK. Sponsor: Canon Inc, Japan
(unpublished report provided by notifier).
Safepharm Laboratories (2004p) C-FG-P: Assessment of the Inhibitory Effect on the Respiration of Activated
Sewage Sludge (Project No. 345/756, 08 July 2004) Safepharm Laboratories Ltd, Shardlow, UK. Sponsor:
Canon Inc, Japan (unpublished report provided by notifier).
United Nations (2003) Globally Harmonised System of Classification and Labelling of Chemicals (GHS).
United Nations Economic Commission for Europe (UN/ECE), New York and Geneva.
FULL PUBLIC REPORT: STD/1182 Page 30 of 30
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