1,3-benzenedimethanamine, epichlorohydrin
File No: NA/666
April 1999
NATIONAL INDUSTRIAL CHEMICALS NOTIFICATION
AND ASSESSMENT SCHEME
FULL PUBLIC REPORT
1,3-Benzenedimethaneamine, Reaction Products with Epichlorohydrin
This Assessment has been compiled in accordance with the provisions of the Industrial
Chemicals (Notification and Assessment) Act 1989 (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 National Occupational Health and
Safety Commission which also conducts the occupational health & safety assessment. The
assessment of environmental hazard is conducted by the Department of the Environment and
the assessment of public health is conducted by the Department of Health and Aged Care.
F o r the purposes of subsection 78(1) of the Act, copies of this full public report may be
inspected by the public at the Library, National Occupational Health and Safety Commission,
92-94 Parramatta Road, Camperdown NSW 2050, between the following hours:
Monday - Wednesday 8.30 am - 5.00 pm
Thursday 8.30 am - 8.00 pm
Friday 8.30 am - 5.00 pm
Copies of this full public report may also be requested, free of charge, by contacting the
Administration Coordinator on the fax number below.
For enquiries please contact the Administration Coordinator at:
Street Address: 92 Parramatta Rd Camperdown, NSW 2050, AUSTRALIA
Postal Address: GPO Box 58, Sydney 2001, AUSTRALIA
Telephone: (61) (02) 9577-9514 FAX (61) (02) 9577-9465
Director
Chemicals Notification and Assessment
NA/666
FULL PUBLIC REPORT
1,3-Benzenedimethaneamine, Reaction Products with Epichlorohydrin
1. APPLICANT
Amtrade International of Level 2, 570 St. Kilda Rd, MELBOURNE, VIC 3004 has submitted
a standard notification statement in support of their application for an assessment certificate
for 1,3-benzenedimethanamine, reaction products with epichlorohydrin.
2. IDENTITY OF THE CHEMICAL
Chemical Name: 1,3-benzenedimethanamine, reaction products with
epichlorohydrin
Chemical Abstracts Service 135470-04-1
(CAS) Registry No.:
Other Names: N,N'-bis-(3-aminomethylbenzyl)-2-hydroxy-
trimethylenediamine (for component where n=1)
2-hydroxy-1,3-bis(N,N'-metaaminomethylbenzyl)-
trimethylene-diamine (for component where n=1)
1,3-xylylenediamine, reaction products with
epichlorohydrin
m-xylenediamine, reaction products with
epichlorohydrin
m-XDA, reaction products with epichlorohydrin
Gaskamine 328
Trade Name: Amtrade A15 (72 ?76 % notified chemical)
Molecular Formula: (C11H16N2O)nC8H12N2 (n = 1 - 12)
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Structural Formula:
H2 N
N N C NH2
H H H2
OH
n = 1 - 12
Molecular Weight: 328.4 (for n = 1); the NAMW for the oligomeric
mixture was not provided
Method of Detection the notified chemical can be detected using HPLC and
and Determination: identified using infrared spectrometry
Spectral Data: IR: 3353, 3297, 3054, 2915, 2848, 1606, 1589, 1486,
1456, 1378, 1157, 1114, 1039, 867, 790, 732, 701 cm-1
3. PHYSICAL AND CHEMICAL PROPERTIES
The notified chemical is oligomeric and contains a range of different molecular weight species,
including up to 28 % of 1,3-benzenedimethanamine. Several of the physico-chemical
properties are estimates based on similar amine compounds. The analogue data are identified
where used.
Appearance at 20癈 clear pale yellow viscous liquid
and 101.3 kPa:
Boiling Point: >200癈
Specific Gravity: ca. 1.14 at 25癈
Vapour Pressure: < 0.004 kPa at 25癈
(value for 1,3-benzenedimethanamine, calculated)
Water Solubility: stated to be insoluble for n > 2
log Pow 3.3
Partition Co-efficient
(n-octanol/water): (analogue data for isophoronediamine)
Hydrolysis as a Function The notified chemical does not contain any
of pH: hydrolysable functional groups
Adsorption/Desorption: see comments below
p K a 11
Dissociation Constant:
(analogue data for diethylamine and triethylamine)
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pH: 11.7 (10 % w/v aqueous N,N'-bis-(3-aminomethyl-
benzyl)-2-hydroxy-trimethylenediamine
Flash Point: 177癈
Flammability Limits: combustible
Autoignition Temperature: not determined
Explosive Properties: not explosive
Reactivity/Stability: The chemical shows reactivity typical of primary and
secondary amines
Comments on Physico-Chemical Properties
While the notified chemical is stated to be insoluble in water for n > 1, the amine groups
present would confer some solubility in water when protonated. This would be expected to
occur to a greater or lesser degree in the environmental pH range of 4-9. The lower MW
moieties would also have a greater potential to be soluble.
I n the oral toxicity study supplied by the notifier, the single component of the reaction
mixture for which n=1, N,N'-bis-(3-aminomethylbenzyl)-2-hydroxy-trimethylenediamine,
was found to be miscible with water and pH values for a number of concentrations are
quoted, ranging between 11.7 (10 % w/v) and 12.7 (90 % w/v).
The nature of the chemical was stated to preclude acquisition of most of the physico-chemical
data pertinent to environmental issues, i.e. water solubility, hydrolytic degradation,
octanol/water partition coefficient and adsorption/desorption characteristics. No data for the
octanol/water partition coefficient was provided. However, the notifier claims that the Pow
value would be similar to that of isophorone diamine, a similarly structured alkylamine; it was
not indicated how the Pow value was calculated. The hydrocarbon content of the chemical
should confer an ability to adsorb onto sediments containing organic material, at least when
unprotonated for the higher MW fraction.
4. PURITY OF THE CHEMICAL
Degree of Purity: 72-76 %
Toxic or Hazardous
Impurities:
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Chemical name: 1,3-benzenedimethanamine
Synonyms: m-XDA, 1,3-xylylenediamine, 1,3-bis(aminomethyl)-
benzene
CAS No.: 1477-55-0
Weight percentage: 24-28 %
On the List of Designated Hazardous Substances (risk
Toxic properties:
phrases not stipulated)
NOHSC exposure standard 0.1 mg/m3 (peak limitation)
with skin notation
Eye: Corrosive. Contact with eyes may cause severe
irritation, and possible eye burns.
Skin: Corrosive. May cause severe irritation and
possible burns. Skin sensitiser
Ingestion: Gastrointestinal irritant.
Inhalation: May cause severe irritation of the
respiratory tract with sore throat, coughing,
shortness of breath and delayed lung oedema.
Chemical name: Oxirane, (chloromethyl)-
Synonyms: epichlorohydrin
CAS No.: 106-89-8
Weight percentage: < 10 ppm
On the NOHSC List of Designated Hazardous
Toxic properties:
Substances with the following risk phrases:
0.1 Conc. 1 %
R23/24/25: Toxic by inhalation, in contact with skin and
if swallowed
R36/38: Irritating to eyes and skin
1 Conc. 10 %
R23/24/25: Toxic by inhalation, in contact with skin and
if swallowed
R34: Causes burns
Non-hazardous Impurities none
(> 1% by weight):
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5. USE, VOLUME AND FORMULATION
The notified chemical is an epoxy curing agent and will be used in Part A of a two part epoxy
coating for application to plastic surfaces.
The notified chemical will not be manufactured in Australia, nor will it be reformulated other
than by mixing in a 3:1 ratio with Part B, and 30 % glycol ether solvent in preparation for
application. The import volume is estimated to be 20 000 kg/year.
6. OCCUPATIONAL EXPOSURE
Routes of Exposure
The notified chemical is a viscous liquid of low volatility. It is a Type 1 category compound
and the system used for handling this chemical is intended to provide total segregation. The
most probable route of exposure will be dermal. The low vapour pressure and viscous nature
of the chemical indicate that inhalation would be unlikely.
Transport and Storage
Transport and storage workers may be involved with the notified chemical for 2-3 hours per
day on 10-15 days per year. The notified chemical will be imported in 200 kg drums. The
drums will be transported directly from the docks to the customer facility where they will be
stored in a chemical warehouse prior to use on the same site. Waterside workers, transport
drivers and warehouse workers would only be exposed to the notified chemical in the case of
an accident involving rupture of the packaging.
Plant Operators
Metered quantities of the notified substance will be pumped or gravity fed from the 200 kg
drums directly into the application machinery. The epoxy resin Part A will be mixed with a
glycol ether solvent before being mixed with Part B. The coating mix will then be sprayed
onto the plastic material using an electrostatic mechanism to minimise overspray. The treated
material will then be heated to 63癈 for 15 minutes within the process line to complete the
curing of the resin before the article is removed. The equipment used for mixing and applying
the epoxy resin will be completely enclosed and automated, so exposure would not occur
during this process. The production area is stated to have local and general ventilation to
remove any vapours which may escape.
Plant operators will be working with the notified chemical for 8 hours per day for up to 250
days per year. In the coated products the notified chemical will be crosslinked and
immobilised within the cured epoxy matrix. The greatest exposure is likely to occur during
drum connection and disconnection, and during cleaning and maintenance of equipment, when
skin contamination may occur due to drips and spills of the chemical.
Cleaning of the equipment will be carried out using a suitable solvent which will be collected
and disposed of to a liquid waste facility by a licensed contractor.
The notifier states that plant operators will be required to wear impervious gloves, coveralls,
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suitable respirator and eye protection during connection and disconnection of containers to
transfer lines and during cleaning and maintenance of equipment.
7. PUBLIC EXPOSURE
There is little potential for exposure of the public to the notified chemical, as it is not
available for retail sale. The public will only come in contact with the coated materials where
the notified chemical will be trapped inside the cured matrix of the coating.
8. ENVIRONMENTAL EXPOSURE
Release
The process of mixing and applying the resin is in a closed system with no exposure to the
environment until the mixture containing the notified chemical is cured.
The cleaning of equipment is expected to lead to some residues (300 kg per year or 1.5 % of
yearly import volume) which will be collected by a licensed waste contractor.
During the surface coating process the notifier estimates that 100 kg or 0.5 % of the yearly
import volume will be released due to accidents or leaks in equipment. Any spillage of the
chemical would be absorbed into sand or other suitable material, and disposed of to landfill.
The Material Safety Data Sheet (MSDS) gives instructions for dealing with spills of the
imported product containing the notified chemical.
Any residue of the notified substance remaining in the 200 L drums, estimated to be 300 kg
a n n u a l l y or 1.5 % of the drum contents, will be mixed with part B of the resin. After
hardening, the drums containing the residues will be disposed of by a licensed contractor to
landfill.
Fate
The notified substance will form part of a surface coating on plastic components and fixed
strongly to the coated articles, thus sharing their fate. At the end of their useful lives these
would be disposed of to landfill, or possibly incinerated.
Released material resulting from the surface coating process would also be placed into landfill.
Solvents used in cleaning of equipment and other activities connected with use of the chemical
are likely to be recycled or disposed of to a liquid waste handling facility where the ultimate
fate of any remaining material would presumably be incineration.
When disposed of to landfill, the highly crosslinked nature of the cured material will preclude
significant leaching, and the chemical would be subject to the slow biodegradation processes
operative in landfill situations.
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Incineration of the notified chemical would result in the production of water and oxides of
carbon and nitrogen.
The notified substance is not expected to bioaccumulate because it will either be protonated in
the environment or reacted with the other part of the surface coating.
9. EVALUATION OF TOXICOLOGICAL DATA
No toxicological data on the notified chemical itself were submitted. Some studies on the
dimer, N,N'-bis-(3-aminomethylbenzyl)-2-hydroxy-trimethylenediamine (MW = 328), which
is a major component of the notified chemical, were available and were included as part of the
submission.
Analogue data for a number of related organic amine compounds have been provided by the
notifier. The data was in the form of readily available compilations of hazardous properties,
from ACGIH (American Conference of Government Industrial Hygienists, 1998), RTECS
(National Institute of Occupational Safety and Health, 1997) and HSDB (National Library of
Medicine, 1997). The analogue chemicals were 1,3-benzenedimethanamine (m-
xylylenediamine, m-XDA) which is the starting material and major impurity (24 - 28 %) in
the notified chemical, isophoronediamine (IPD), diethylenetriamine (DETA) and
triethylenetetramine (TETA).
The analogue data is accepted in this report as a suitable surrogate for the notified chemical.
Consequently, the findings are taken as representing the toxicity of the notified chemical.
9.1 Acute Toxicity
Summary of the acute toxicity of 1,3-benzenedimethanamine, reaction products
with epichlorohydrin, and related compounds
Test substance Species Outcome Reference
Acute oral toxicity
dimer rat LD50 = 646 mg/kg (males) (Nagai & Hirota,
LD50 = 744 mg/kg (females) 1983a)
Acute dermal toxicity
m-XDA rabbit LD50 = 2000 mg/kg ACGIH
DETA LD50 = 1090 mg/kg ACGIH, RTECS
TETA LD50 = 805 mg/kg RTECS
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Acute inhalation toxicity
m-XDA rat LC50 = 3.75 mg/L (1 hour, ACGIH
equivalent to LC50 of 1.9 mg/L
for 4 hours)
DETA no deaths following 300 ppm ACGIH
exposure for 8 hours
Skin irritation
dimer rabbit corrosive (Nagai & Hirota,
1983b)
m-XDA corrosive ACGIH
DETA moderate to severe irritation RTECS
TETA severe irritation RTECS
Eye irritation
m-XDA rat exposure to aerosol produced ACGIH
ocular irritation and lacrimation
DETA human severe corneal injury after ACGIH
application of a 15 % solution
S k i n sensitisation
m-XDA human reported to be a potent ACGIH
IPD sensitiser (Patussi et al., 1995)
sensitiser (Guerra et al., 1992)
DETA ACGIH
TETA respiratory and skin sensitiser HSDB
marked sensitisation in 6 out of
m-XDA guinea pig 20 workers in one factory RTECS
mild sensitiser
The toxicological properties of the notified chemical would be expected to be dominated by
the presence of primary and secondary amine groups. Of the analogue compounds, m-XDA
would be expected to be the closest to the notified chemical in toxicological properties, having
the same type of primary aromatic amines. DETA and TETA both contain secondary amines
as well. The overall toxicological properties of the four analogue chemicals show a similar
p a t t e r n , and so it would be expected that the notified chemical would also have similar
toxicological properties.
The notified chemical is of significantly higher molecular weight than any of the analogue
chemicals and should not be absorbed across biological membranes as readily as the analogues
are.
9.1.1 Oral Toxicity (Nagai & Hirota, 1983a)
The test was conducted using 2-hydroxy-1,3-bis(N,N'-
metaaminomethylbenzyl)trimethylene-diamine (the dimer; N,N'-bis-(3-aminomethylbenzyl)-
2-hydroxy-trimethylenediamine), a single component of Amtrade A15. The test material
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contained only 0.69 % (w/w) 1,3-benzenedimethanamine, rather than the 24-28 % (w/w) in
the notified chemical. The aqueous solution used in the test had a pH of 11.5.
Species/strain: rat/Wistar
Number/sex of animals: 10/sex/dose
Observation period: 14 days
Method of administration: gavage, 10 % (w/v) aqueous solution
Dose range: males: 415, 490, 578, 682, 805, 950 mg/kg
females: 490, 578, 682, 805, 950, mg/kg
Test method: OECD TG 401 (Organisation for Economic Cooperation and
Development, 1987)
Mortality: males
dose (mg/kg) mortality
0 (control) 0/10
415 0/10
490 2/10
578 4/10
682 3/10
805 9/10
950 10/10
females
dose (mg/kg) mortality
0 (control) 0/10
490 0/10
578 1/10
682 4/10
805 7/10
950 8/10
1121 10/10
Clinical observations: transient signs of excitement were observed in the animals
immediately after administration; sudden collapse due to
ataxia resulting in death was seen in a number of the animals,
generally within two hours of administration and always
within the first day; partial recovery from the symptoms
was seen in the surviving animals by the second day
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Morphological findings: the rats which died during the test exhibited high fusion of
mucous membranes of the stomach and intestinal canal, and
sligh pulmonary congestion; no major changes in other
organs were reported; in the animals sacrificed at the end of
the observation period no noticeable abnormalities were
found
LD 50: males: 646 mg/kg, females: 744 mg/kg
Result: the test substance was of low acute oral toxicity in rats
9.1.2 Dermal Toxicity
A summary of analogue data was provided by the notifier. The findings are tabulated in
Section 9.1 above.
9.1.3 Inhalation Toxicity
A summary of analogue data was provided by the notifier. The findings are tabulated in
Section 9.1 above.
9.1.4 Skin Irritation (Nagai & Hirota, 1983b)
The test was conducted using 2-hydroxy-1,3-bis(N,N'-
metaaminomethylbenzyl)trimethylene-diamine (the dimer; N,N'-bis-(3-aminomethylbenzyl)-
2-hydroxy-trimethylenediamine), a single component of Amtrade A15. The test material
contained only 0.69 % (w/w) 1,3-benzenedimethanamine, rather than the 24-28 % (w/w) in
the notified chemical.
Species/strain: rabbit/Japanese native strain
Number/sex of animals: 6 male
Observation period: 7 days
Method of administration: semi-occlusive patch; 0.5 mL neat liquid; intact and abraded
skin for both 4 hours and 24 hours; after this time, the
remaining material was removed with warm water and gauze
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Test method: Draize method (Draize et al., 1944)
Draize scores (Draize, 1959):
4 hour exposure
Intact skin
Time after Animal #
treatment 1 2 3 4 5 6
(hours)
Erythema
0a
4 0 0 0 0 0
24 0 0 0 0 0 0
48 0 0 0 0 0 0
Oedema
4 0 0 0 0 0 0
24 0 0 0 0 0 0
48 0 0 0 0 0 0
Abraded skin
Time after Animal #
treatment 1 2 3 4 5 6
(hours)
Erythema
4 0 0 0 1 0 0
24 0 0 0 1 0 1
48 0 0 0 1 0 1
Oedema
4 0 0 0 0 0 0
24 0 0 0 0 0 0
48 0 0 0 0 0 0
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24 hour exposure
Intact skin
Time after Animal #
treatment 1 2 3 4 5 6
(days)
Erythema
1 2 0 0 2 0 2
2 2 0 0 0 0 3
3 2 0 0 2 1 3
Oedema
1 3 3 0 0 0 1
2 2 0 0 2 0 1
3 1 0 0 1 0 0
Abraded skin
Time after Animal #
treatment 1 2 3 4 5 6
(days)
Erythema
1 1 0 1 2 1 2
2 1 0 0 2 1 3
3 1 0 0 3 2 3
Oedema
1 0 3 0 2 0 1
2 0 0 0 2 0 1
3 0 0 0 0 0 0
a
see Attachment 1 for Draize scales
Comment: in addition to oedema and erythema, the animals were scored
for bleeding and necrosis; in the area which had been exposed
to the notified chemical for 24 hours, three out of six animals
showed necrosis of intact skin while one animal also showed
bleeding, and five of the animals showed necrosis of the
abraded skin area; only a topical corrosive change on the
abraded area of one animal was observed for the area exposed
for 4 hours
the report indicated that the difference between the 4 hour
and 24 hour exposed regions indicates that the test substance
permeates through the skin relatively slowly; the corrosive
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effects after 24 hour exposure were to be expected on the
basis of the pKa of the test material
Result: the test substance was a slight irritant to the skin of rabbits
on the basis of the standard test, but is classified as corrosive
o n the basis of the pH of the aqueous solutions (11.7 for
10 % w/v, 12.7 for 90 % w/v).
9.1.5 Eye Irritation
A summary of analogue data was provided by the notifier. The findings are tabulated in
Section 9.1 above.
9.1.6 S k i n Sensitisation
A summary of analogue data was provided by the notifier. The findings are tabulated in
Section 9.1 above. Two case reports of sensitisation by exposure to IPD have been provided
as part of the notification package.
A 53 year old male with a four year history laying impermeable floors coated with epoxy
resins including IPD showed an eruption of the face which disappeared on spending two
weeks away from work. The eruption recurred 2 months later, and disappeared with
treatment with oral corticosteroids and time away from work. He tried four more times to
recommence work after this, with dermatitis reappearing each time. Patch testing with the
chemicals used in the epoxy mixtures gave a positive result for IPD (Patussi et al., 1995).
A 36 year old male with a ten year history as a wine vat varnisher, with dermatitis of the
hands and face, a 44 year old male with an eruption of the face following use of and adhesive,
and a 37 year old female worker in a car factory with dermatitis on the hands and a history of
exposure to plastics, rubbers and adhesives, all tested positive to IPD in patch testing (Guerra
et al., 1992).
No skin sensitisation study of the notified chemical has been provided. All of the amines for
which analogue data has been provided have been reported to be human skin sensitisers. On
this basis, the notified chemical must be classified as a skin sensitiser.
9.2 Repeated Dose Toxicity (Greenman et al., 1996)
A published report of a 92 day oral subchronic study using the dihydrochloride of TETA has
been supplied by the notifier as analogue data. It is not possible to draw more than indicative
conclusions about the notified chemical from this analogue study. The main reason is that
TETA is a strong chelating agent, and is used for reducing tissue copper levels in some cases
of Wilson's disease. It is therefore likely that many of the subchronic effects caused by
TETA will be due to the changes in body metal ion concentrations. The notified chemical
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does not have the structural features which make TETA such a potent chelating agent, and the
in vivo effects would therefore be expected to be very different. The other reason for being
cautious in extrapolating the effects for the analogue chemical is that in subchronic toxicity,
the metabolites of the administered compound play an important role. TETA has a very
different carbon skeleton to the notified chemical and a very different group of metabolites
would be expected.
In mice administered 0, 120, 600 or 3000 ppm of TETA.2HCl in drinking water, a number of
s y m p t o m s were reported to not be related to copper deficiency, unless localised. These
included inflammation of the lung interstitium, haematopoietic cell proliferation of the spleen,
liver periportal fatty infiltration, kidney weight reduction, reduced renal cytoplasmic
vacuolation and body weight gain reduction.
In rats administered the same dose, the only sign that was not considered related to the effects
on copper levels was a dose dependent increase in uterine dilation in the females. On the basis
of this effect, the NOAEL for the study was 120 ppm, equivalent to 55 mg/kg/day for males
and 70 mg/kg/day for females.
It is not clear which effects would be common to a range of amines and which will be specific
to the particular compound, and the repeated dose toxicity of the notified chemical even as a
hydrochloride salt could be quite different to that of TETA.2HCl.
9.3 Genotoxicity
9.3.1 Salmonella typhimurium Reverse Mutation Assay (Mitsubishi Gas Chemical
Company, 1983)
The test was conducted using 2-hydroxy-1,3-bis(N,N'-
metaaminomethylbenzyl)trimethylene-diamine (the dimer; N,N'-bis-(3-aminomethylbenzyl)-
2-hydroxy-trimethylenediamine), a single component of Amtrade A15. The test material
contained only 0.69 % (w/w) 1,3-benzenedimethanamine, rather than the 24-28 % (w/w) in
the notified chemical.
Strains: Salmonella typhimurium: TA98, TA100, TA1535, TA1537,
TA1538
Escherichia coli: WP2 uvrA
10, 50, 100, 500, 1000 and 5000 礸/plate
Concentration range:
Metabolic Activation rat liver S9 fraction from animals pretreated with PB-5.6 BF
System:
Test method: OECD TG 471 (Organisation for Economic Cooperation and
Development, 1983)
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N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG); 3 礸/plate
Positive controls
璗A100; 2 礸/plate ?E. coli WP2 uvrA; 5 礸/plate ?br>
TA1535 (without metabolic activation)
2-nitro-fluorene (2-NF) 1 礸/plate ?TA 98; 2 礸/plate 璗A
1538, (without metabolic activation)
9-aminoacridine (9-AA): 80 礸/plate ?TA1537 (without
metabolic activation)
2-aminoanthracene (2-AA): 0.5 礸/plate - TA100, TA98,
TA1538; 2 礸/plate ?TA1535, TA1537; 80 礸/plate ?E.
coli WP2 (with metabolic activation)
Comment: increased numbers of revertant colonies were not observed
for any strain at any dose either in the presence or absence
of metabolic activation
toxic effects occurred both in the presence and absence of
metabolic activation for the highest dose used for all strains
and at 1000 礸/plate for strains TA1535, TA1537 and
TA1538 in the absence of metabolic activation
the positive controls produced clear positive results
indicating that the test system responded appropriately
Result: no mutagenicity was observed for any of the strains in the
presence or absence of metabolic activation
9.3.2 Analogue Genotoxicity Results
The notifier provided a reference which described the genotoxicity of a number of
alkylamines, ethylenediamine (EDA), aminoethylethanolamine (AEEA), aminoethyl-
piperazine (AEP), DETA, TETA and tetraethylenepentamine (TEPA). Among the
compounds tested, only triethylenetetramine (TETA) was considered to be mutagenic
(Leung, 1994).
Test Result
EDA AEEA AEP DETA TETA TEPA
Salmonella typhimurium N N N N Y N
reverse mutation
sister chromatid exchange N N Y N Y Y
unscheduled DNA N N N N Y Y
synthesis
in vivo micronucleus N N I N N N
gene mutation assay N N I N N N
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N = negative result Y = positive result I = inconclusive result
The clearest genotoxicity results, for TETA, corresponded to a positive salmonella
typhimurium reverse mutation assay. Despite some positive findings in in vitro assays, the
lack of positive finding in in vivo studies suggests that the class of chemicals is at most
weakly mutagenic.
9.4 Overall Assessment of Toxicological Data
The notifier has indicated that Amtrade A15 is classified as a category I hazardous substance.
The acute oral toxicity of the tested component of the notified chemical is low. The analogue
data indicates that the acute dermal toxicity is likely to be moderate. On the basis of the
analogue data, the inhalation toxicity is likely to be moderate. The LD50 values for oral
toxicity of the dimer, the LD50 values for dermal toxicity of the analogue compounds and
LC50 value for inhalation of the analogue compounds indicates that the risk phrase R20/21/22
`Harmful by inhalation, in contact with skin and if swallowed' should be applied.
The NOHSC exposure standards for m-XDA and DETA have skin notations, indicating
potential for skin absorption. As the notified chemical contains similar functional groups, the
lower molecular weight components of the notified chemical may also be absorbed through
the skin. The higher molecular weight components would be too large for skin absorption.
The results of the skin irritation study showed the component of the notified chemical to be
corrosive when applied for 24 hours. The standard test using 4 hour exposure resulted in only
slight irritation being observed. On the basis of the structure of the chemical, it is expected to
be strongly basic (analogous chemicals having a pKa of 11). In the Approved Criteria for
Classifying Hazardous Substances (Approved Criteria) (National Occupational Health and
Safety Commission, 1994a) it is stated that a chemical with a pH of 11.5 or greater should be
classified as corrosive.
It was noted in the skin irritation study that the corrosive effects required comparatively long
exposures to develop. It was suggested that the skin permeability is slow, which is reasonable
as the molecular weight of the substance tested is 328.4. The notified chemical should be
classified as corrosive with the risk phrase R34 `Causes burns' applied. The product in which
the notified chemical is imported also contains 24-28 % (w/w) of the lower molecular weight
amine, m-XDA, as a consequence of the manufacturing process. Therefore the slow skin
permeability of the dimer which was used in the test will not be representative of the product
Amtrade A15. Corrosive substances are also considered assumed to cause serious eye
damage.
Chemicals of the organic amine class of chemicals to which the notified chemical belongs are
commonly found to be skin sensitisers, and all of the analogue chemicals for which data was
provided by the notifier were subject to reports of occupational skin sensitisation. The
notified chemical should therefore also be considered a skin sensitiser with the risk phrase
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R43 `May cause sensitisation by skin contact' applied.
The analogue data which was provided for repeat dose toxicity could not be extrapolated to
cover the notified chemical, due to significant structural differences. Therefore, on the
available analogue data, the effects of prolonged or repeated exposure to the notified chemical
can be regarded as unknown. The notified chemical will not be used in neutralised or highly
diluted form, and the repeat exposure should be limited by the serious effects of acute
exposure to the chemical.
The component of the notified chemical gave a negative result in a Salmonella typhimurium
reverse mutation assay. A report on the mutagenic potential of a number of organic amines
showed that the class of chemicals is likely to be at most weakly mutagenic. Therefore, it is
unlikely that the notified chemical will be a strong mutagen.
10. ASSESSMENT OF ENVIRONMENTAL EFFECTS
The following ecotoxicity studies have been supplied by the notifier. The tests were carried
out according to OECD Test Methods (Organisation for Economic Co-operation and
Development, 1995-1996)
Both test reports note that the notified chemical was dispersed in reverse osmosis water to
make the stock solutions of 1 g/L (fish) and 128 mg/L (bacteria). The toxicity of the notified
chemical might be underestimated as it is not known what proportion of the dispersed
material was dissolved. Given that some of the test substance is likely to be in solution,
particularly that fraction with a lower MW, the true toxicity is likely to be much higher.
Test Species Results
96 h acute toxicity Golden orfe (Leuciscus idus) LC50 = 4 mg/L
NOEC 1.8 mg/L
(Wetton, 1997)
EC10 0.23 mg/L
16 h inhibition Bacteria (Pseudomonas putida)
EC50 0.42 mg/L
(Mead, 1997)
NOEC = 0.16 mg/L
* NOEC - no observable effect concentration
Fish
A 96 hour toxicity test, performed in accordance with the test guidelines, demonstrated that
the notified chemical had toxic effects on the test fish at nominal concentrations of
> 1.8 mg/L. The report notes that a cosolvent was used and a solvent control was included.
Microorganisms
The inhibitory effect of the notified chemical on bacterial growth was investigated in a
respiration test. The notified chemical showed inhibitory effects on cell growth at test
concentrations greater than 0.16 mg/L after 16 hours of exposure.
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Conclusions
The ecotoxicity data for the notified chemical indicate that it is moderately toxic to fish and
highly toxic to bacteria (Pseudomonas putida).
11. ASSESSMENT OF ENVIRONMENTAL HAZARD
The notified substance in its unreacted form may have some potential to be water soluble
particularly the lower MW fraction when protonated. In case of exposure to the aquatic
environment from accidental spillage in transport, there may be some risk of toxicity to
aquatic species and bacteria.
The notified substance is not expected to bioaccumulate because it will either be protonated in
the environment or reacted with the other part of the surface coating.
The environmental hazard from the notified chemical is however considered low when it is
reacted to form a surface coating on plastic components. It is not expected to be mobile or
achieve any significant environmental exposure. The residue resulting from use of the material
would be reacted with the other part and share a similar fate and hazard as the surface coating
on the plastic components at the end of their service. These will be placed in landfill with
little hazard expected as a consequence of leaching.
12. ASSESSMENT OF PUBLIC AND OCCUPATIONAL HEALTH AND SAFETY
EFFECTS
The notified chemical is a category I hazardous substance. The imported material, Amtrade
A15, which contains up to 28 % of 1,3-benzenedimethanamine (m-XDA) as a consequence of
the manufacturing process, is also a category I hazardous substance.
The acute oral toxicity of the tested component of the notified chemical is low. From the
toxicological properties of related compounds, the notified chemical is expected to be of
moderate acute dermal and acute inhalation toxicity. The lower molecular weight components
of the notified chemical can be expected on the basis of the properties of related materials to
be absorbed through the skin. The chemical is classified as corrosive because of its basicity,
although the corrosive action was shown to be slow. The mixture of reaction products, which
includes m-XDA, will be classified as corrosive. On the basis of analogue data, the notified
chemical is a skin sensitiser. The risk phrases R20/21/22 `Harmful by inhalation, in contact
with skin and if swallowed', R34 `Causes burns' and R43 `May cause sensitisation by skin
contact' are therefore required.
Insufficient data was supplied in the notification on which to base an assessment of the
effects of prolonged exposure to the notified chemical. The notified chemical is unlikely to be
used in a diluted or neutralised form, where chronic exposure would be possible without
serious acute effects. The notified chemical was not mutagenic in a Salmonella typhimurium
reverse mutation assay, and similar chemicals were found to be at most, weak mutagens. The
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main hazard associated with this chemical is therefore likely to be the serious acute effects
associated with the high basicity of the amine groups.
The notified chemical may be recommended to the National Occupational Health and Safety
Commission for consideration for inclusion in the NOHSC List of Designated Hazardous
Substances.
Considering the high acute hazard (systemic and topical) associated with the notified
chemical, stringent measures to prevent occupational exposure are required. The occupational
health and safety data provided with this notification indicated that this will be the case. The
equipment used for mixing and applying the epoxy resin will be completely enclosed and
automated. The resin mixture will remain in the enclosed system until it is heat treated to
effect crosslinking, which will immobilise the notified chemical as part of the resin matrix. The
most significant exposure is therefore likely to occur during drum connection and
disconnection, and during cleaning and maintenance of equipment, where skin contamination
may occur. The m-XDA contained in the mixture of reaction products may also pose an
inhalation hazard.
The production area is stated to have local and general ventilation to remove any solvent
vapours which may escape. The notifier states that plant operators will be required to wear
impervious gloves, coveralls, suitable respirator and eye protection during connection and
disconnection of containers to transfer lines and during cleaning and maintenance of
equipment.
Therefore the risk of adverse health effects arising from exposure to the notified chemical are
confined to possible skin irritation and sensitisation and eye irritation during operations
outside the main process, which is fully enclosed. Due to the toxic nature of the notified
chemical, brief exposures may be harmful.
The imported product also contains m-XDA as a major constituent. This chemical has a low
NOHSC exposure standard (0.1 mg/m3 peak limitation) with skin notation. Stringent
precautions are required to minimise exposure to the product Amtrade A15.
Workers other than the production workers applying the resin should not be exposed to the
notified chemical, as it will be imported and transferred to the site where it is used in sealed
containers, and will not be generally available. It will not be available for retail sale.
There is negligible potential for public exposure to the notified chemical arising from its use as
a curing agent as part of epoxy coatings applied to plastic surfaces. There will be public
contact with the notified chemical when incorporated into products, but since the notified
chemical is an integral part of the epoxy matrix, no significant exposure should occur, and the
pattern of exposure will be intermittent. It is therefore considered that the notified chemical
will not pose a significant hazard to public health.
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13. RECOMMENDATIONS
To minimise occupational exposure to 1,3-benzenedimethanamine, reaction products with
epichlorohydrin, the following guidelines and precautions should be observed:
Safety goggles should be selected and fitted in accordance with Australian Standard
?br>
(AS) 1336 (Standards Australia, 1994) to comply with Australian/New Zealand
Standard (AS/NZS) 1337 (Standards Australia/Standards New Zealand, 1992);
Industrial clothing should conform to the specifications detailed in AS 2919
?br>
(Standards Australia, 1987) and AS 3765.1 (Standards Australia, 1990);
Impermeable gloves should conform to AS/NZS 2161.2 (Standards
?br>
Australia/Standards New Zealand, 1998);
All occupational footwear should conform to AS/NZS 2210 (Standards
?br>
Australia/Standards New Zealand, 1994);
Spillage of the notified chemical should be avoided. Spillages should be cleaned up
?br>
promptly with absorbents which should be put into containers for disposal;
Good personal hygiene should be practised to minimise the potential for ingestion;
?br>
A copy of the MSDS should be easily accessible to employees.
?br>
The following regulatory action is recommended:
The notified chemical may be recommended to NOHSC for consideration for an
?br>
exposure standard;
The notified chemical may be recommended to the National Occupational Health and
?br>
Safety Commission for consideration for inclusion in the NOHSC List of Designated
Hazardous Substances.
14. MATERIAL SAFETY DATA SHEET
The MSDS for the notified chemical was provided in a format consistent with the National
Code of Practice for the Preparation of Material Safety Data Sheets (National Occupational
Health and Safety Commission, 1994b).
T h i s MSDS was provided by the applicant as part of the notification statement. It is
reproduced here as a matter of public record. The accuracy of this information remains the
responsibility of the applicant.
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15. REQUIREMENTS FOR SECONDARY NOTIFICATION
Under the Act, secondary notification of the notified chemical shall be required if any of the
circumstances stipulated under subsection 64(2) of the Act arise. No other specific
conditions are prescribed.
16. REFERENCES
American Conference of Government Industrial Hygienists (1998). TLVs and Other
Occupational Exposure Values.
Draize JH (1959) Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics.
Association of Food and Drug Officials of the US, 49 : 2-56.
Draize JH, Woodard GC & Calvery HO (1944) J. Pharmacol. Expt. Therapeut., 82 : 377.
Greenman DL, Morrissey RL, Blakemore W, et al. (1996) Subchronic Toxicity of
Triethylenetetramine Dihydrochloride in B6C3F1 Mice and F344 Rats. Fundamental and
Applied Toxicology, 29 : 185-193.
Guerra L, Vincenzi C, Bardazzi F, et al. (1992) Contact Sensitization Due to
Isophoronediamine. Contact Dermatitis, 27 : 52-53.
Leung H-W (1994) Evaluation of the Genotoxic Potential of Alkyleneamines. Mutation
Research, 320 : 31-43.
Mead C (1997) Gaskamine 328: Acute Toxicity to Bacteria (Pseudomanas putida), Project
No. 930/022, Safepharm Laboratories Ltd, Derby UK.
Mitsubishi Gas Chemical Company I (1983) Mutagenic Evaluation of 2-hydroxy-1,3-
bis(N,N'-metaaminomethylbenzyl)trimethylenediamine, Project No. Niigata, Japan.
Nagai T & Hirota M (1983a) Acute Toxicity Test of N,N'-bis(3-aminomethylbenzyl)-2-
hydroxypropane-1,3-diamine Using Rats, Project No. Mitsubishi Gas Chemical Company,
Inc., Niigata, Japan.
Nagai T & Hirota M (1983b) Primary Skin Irritation Test on Albino Rabbits Using 2-
hydroxy-1,3-bis(N,N'-metaaminomethylbenzyl)trimethylenediamine, Project No. Mitsubishi
Gas Chemical Company, Inc., Niigata, Japan.
National Institute of Occupational Safety and Health (1997). Registry of Toxic Effects of
Chemical Substances. 1998.
National Library of Medicine (1997). Hazardous Substances Data Base. 1997.
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National Occupational Health and Safety Commission (1994a) Approved Criteria for
Classifying Hazardous Substances [NOHSC:1008(1994)]. Australian Government Publishing
Service, Canberra.
National Occupational Health and Safety Commission (1994b) National Code of Practice for
the Preparation of Material Safety Data Sheets [NOHSC:2011(1994)]. Australian
Government Publishing Service, Canberra.
Organisation for Economic Cooperation and Development (1983) Genetic Toxicology:
Salmonella typhimurium, Reverse Mutation Assay, Guideline 471. OECD Guidelines for
Testing of Chemicals. Section 4: Health Effects.
Organisation for Economic Cooperation and Development (1987) Acute Oral Toxicity,
Guideline 401. OECD Guidelines for Testing of Chemicals. Section 4: Health Effects.
Organisation for Economic Co-operation and Development (1995-1996) OECD Guidelines
for the Testing of Chemicals on CD-Rom. OECD, Paris.
Patussi V, Kokeli F & Buttazzi P (1995) Occupational Airborne Allergic Contact Dermatitis
Due to 3-aminomethyl-3,5,5-trimethylcyclohexylamine. Contact Dermatitis, 32 : 239.
Standards Australia (1987) Australian Standard 2919-1987, Industrial Clothing. Standards
Association of Australia, Sydney.
Standards Australia (1990) Australian Standard 3765.1-1990, Clothing for Protection against
Hazardous Chemicals Part 1 Protection against General or Specific Chemicals. Standards
Association of Australia, Sydney.
Standards Australia (1994) Australian Standard 1336-1994, Eye protection in the Industrial
Environment. Standards Association of Australia, Sydney.
Standards Australia/Standards New Zealand (1992) Australian/New Zealand Standard 1337-
1992, Eye Protectors for Industrial Applications. Standards Association of
Australia/Standards Association of New Zealand, Sydney/Wellington.
Standards Australia/Standards New Zealand (1994) Australian/New Zealand Standard 2210-
1994, Occupational Protective Footwear. Standards Association of Australia/Standards
Association of New Zealand, Sydney/Wellington.
Standards Australia/Standards New Zealand (1998) Australian/New Zealand Standard 2161.2-
1998, Occupational protective gloves, Part 2: General requirements. Standards Association of
Australia, Sydney.
Wetton PM (1997) Gaskamine 328: Acute Toxicity to Golden Orfe (Leuciscus idus), Project
No. 930/022, Safepharm Laboratories Ltd, Derby UK.
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Attachment 1
The Draize Scale for evaluation of skin reactions is as follows:
Erythema Formation Rating Oedema Formation Rating
No erythema 0 No oedema 0
Very slight erythema (barely 1 Very slight oedema (barely perceptible) 1
perceptible)
Well-defined erythema 2 Slight oedema (edges of area well- 2
de fine d by definite raising
Moderate to severe erythema 3 Moderate oedema (raised approx. 1 mm) 3
Severe erythema (beet redness) 4 Severe oedema (raised more than 1 mm 4
and extending beyond area of
exposure)
The Draize scale for evaluation of eye reactions is as follows:
CORNEA
Opacity Rating Area of Cornea involved Rating
No opacity 0 none 25% or less (not zero) 1
Diffuse area, details of iris clearly 1 slight 25% to 50% 2
visible
Easily visible translucent areas, 2 mild 50% to 75% 3
d e t a i l s of iris slightly obscure
Opalescent areas, no details of iris 3 Greater than 75% 4
visible, size of pupil barely moderate
discernible
Opaque, iris invisible 4 severe
CONJUNCTIVAE
Redness Rating Chemosis Rating Discharge Rating
Vessels normal 0 none No swelling 0 none No discharge 0 none
Vessels definitely 1 Any swelling above 1 slight Any amount different 1 slight
injected above normal slight normal from normal
More diffuse, deeper 2 mod. O b v i o u s swelling 2 mild Discharge with 2 mod.
crimson red with with partial eversion m o i s t e n i n g of lids and
i n d i v i d u a l vessels not o f lids adjacent hairs
e a s i l y discernible
Swelling with lids 3 mod. Discharge with 3 severe
Diffuse beefy red 3 severe half-closed m o i s t e n i n g of lids and
hairs and considerable
Swelling with lids 4 severe area around eye
half-closed to
c o m p l e t e l y closed
IRIS
Values Rating
Normal 0 none
Folds above normal, congestion, swelling, circumcorneal injection, iris reacts to light 1 slight
No reaction to light, haemorrhage, gross destruction 2 severe
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