National Industrial Chemicals Notification and
Assessment Scheme
Triglycidylisocyanurate (TGIC)
__________________________________________________
Priority Existing Chemical
Secondary Notification Assessment
Report No. 1S
February 2001
Commonwealth of Australia 2000
ISBN 0 642 455 236
This work is copyright. Apart from any use as permitted under the Copyright Act 1968, no
part may be reproduced by any process without prior written permission from AusInfo.
Requests and inquiries concerning reproduction and rights should be addressed to the
Manager, Legislative Services, AusInfo, GPO Box 1920, Canberra, ACT 2601 or by email
to: cwealthcopyright@dofa.gov.au
Secondary Notification Assessment
ii
Preface
This assessment was carried out under the National Industrial Chemicals Notification and
Assessment Scheme (NICNAS). This Scheme was established by the Industrial Chemicals
(Notification and Assessment) Act 1989 (the Act), which came into operation on 17 July
1990.
The principal aim of NICNAS is to aid in the protection of people at work, the public and
the environment from the harmful effects of industrial chemicals, by assessing the risks
associated with the manufacture and use of such chemicals.
NICNAS is administered by the National Occupational Health & Safety Commission
(NOHSC) and assessments are carried out in conjunction with Environment Australia (EA)
and the Therapeutic Goods Administration (TGA), who carry out the environmental and
public health assessments, respectively. NICNAS has two major programs: one focusing
on risks associated with new chemicals, prior to importation or manufacture and the other
focusing on existing chemicals already in use in Australia.
As there are many thousands of existing industrial chemicals in use in Australia, NICNAS
has an established mechanism for prioritising and assessing these chemicals. Such
chemicals are referred to as Priority Existing Chemicals.
The scope of priority existing chemical assessments permits recommendations to be made
which will assist in the management of the workplace, public health and environmental
risks. Recommendations may be directed to industry (employers and employees) and/or
other Federal and State/Territory regulatory authorities. NICNAS cannot make regulatory
decisions, which fall within the responsibility of other regulatory authorities, and therefore
recommendations can only be given effect through consideration of risk management
practices and processes by those agencies/authorities charged with regulatory decision-
making.
Where further information becomes available after publication of a Priority Existing
Chemical report and/or where certain prescribed circumstances occur, as stipulated under
Section 64(2) of the Act, the Director (Chemicals Notification and Assessment) may
require a reassessment of the hazards of the chemical under `secondary notification
provisions' (Division 6) of the Act. This Full Public Report has been prepared in
accordance with these provisions.
Under Section 40 of the Act, a public comment process is also undertaken for secondary
notification assessment reports.
For the purposes of Section 78(1) of the Act, copies of Full Public Reports for New and
Existing Chemical assessments may be inspected by the public at the library of the National
Occupational Health and Safety Commission (NOHSC). Summary Reports are published
in the Commonwealth Chemical Gazette, which is also available to the public at the
NOHSC library.
Copies of this and other priority existing chemical reports are available from NICNAS
either by using the prescribed application form at the back of this report, or directly from
the following address:
Triglycidylisocyanurate iii
GPO Box 58
Sydney
NSW 2001
AUSTRALIA
International Tel: +61 (02) 9577 9437
Free Call: 1800 638 528
Fax: +61 (02) 9577 9465 or +61 (02) 9577 9465 9244
Other information about NICNAS (also available on request) includes:
? NICNAS Service Charter;
? information sheets on NICNAS Company Registration;
? information sheets on Priority Existing Chemical and New Chemical assessment
programs;
? application forms for New Chemical and Priority Existing Chemical assessments;
? application form for the Australian Inventory of Chemical Substances (AICS)
? subscription details for the Commonwealth Chemical Gazette; and
? subscription details for the NICNAS Handbook for Notifiers.
Priority Existing Chemical and New Chemical Summary Reports together with other
information on NICNAS activities can be found on the NICNAS Web site at:
http://www.nicnas.gov.au
Secondary Notification Assessment
iv
Overview
Triglycidylisocyanurate (TGIC) was the subject of an assessment as a Priority Existing
Chemical and a full public report was published in April 1994. As a result of new data
becoming available, the chemical has been reassessed under the secondary notification
provisions of the Industrial Chemicals (Notification and Assessment) Act 1989 (the Act).
This assessment has evaluated new animal studies including oral toxicity/fertility,
carcinogenicity and contact hypersensitivity studies, in addition to human case reports of
respiratory sensitisation. A new biodegradability study was also provided. The
consequences of the new data on the health and environmental hazard and risk assessments
were evaluated.
The original TGIC report, (TGIC-1), concluded that TGIC is a hazardous substance, being
toxic by oral and inhalational routes (R23/25), a skin sensitiser (R43), genotoxic (R46) and
capable of causing serious eye damage (R41).
New human data confirmed that TGIC is a skin sensitiser and also demonstrated that it is a
respiratory sensitiser. Repeated dose toxicity studies in animals indicate that TGIC causes
severe effects after repeated exposure. The principal effects were significantly lower
bodyweight, mastocytosis in lymph nodes and depletion of spleen lymphoid cells. TGIC
was not carcinogenic in male rats exposed to TGIC by gavage. However, the carcinogenic
potential of TGIC in female rats has not been studied.
Induction of chromosomal aberrations and cytotoxicity in mouse spermatogonia raised
concerns in the original report, regarding potential reproductive effects of TGIC. A recent
fertility study in male rats provides some evidence that TGIC does not affect male fertility.
However, the potential for TGIC to affect female fertility and offspring growth and fertility
has not been tested.
As reported in TGIC-1, TGIC residues released to the environment are expected to rapidly
degrade due to the epoxide nature of the compound. The reactivity of TGIC precludes any
possibility of bioaccumulation. In the aquatic environment, persistence is expected to be
limited.
The occupational risk assessment in TGIC-1 concluded that TGIC is unlikely to cause
adverse health effects if appropriate control measures, safe work practices and atmospheric
monitoring strategies are implemented. The new data showing that TGIC is a respiratory
sensitiser confirms the need to maintain occupational exposure levels to the lowest
practicable level. The new repeated dose data goes some way towards predicting the long
term health effects of occupational exposure to TGIC. However, there remain several data
gaps, and therefore the potential for chronic health effects is not fully understood.
The new data does not change the public health and environment conclusions of the
original report. TGIC is unlikely to present a risk to the public or the environment.
Recommendations
Further to the new data provided under this assessment, and in accordance with the health
effects criteria detailed in the National Occupational Health and Safety Commission's
(NOHSC) Approved Criteria for Classifying Hazardous Substances (NOHSC, 1999),
Triglycidylisocyanurate v
TGIC should be classified with additional risk phrases: `may cause sensitisation by
inhalation' (R42) and `danger of serious damage to health by prolonged exposure if
swallowed' (R48).
Consistent with good occupational health and safety principles, all occupational control
measures including atmospheric monitoring, as recommended in the TGIC-1 report should
be adhered to.
It is recommended that employers conduct an assessment of the risks to the health of
employees from exposure to TGIC. Where there is a likelihood of sensitisation occurring
in workers, then a health surveillance program should be provided.
Secondary Notification Assessment
vi
Contents
PREFACE iii
OVERVIEW v
ACRONYMS AND ABBREVIATIONS ix
1. INTRODUCTION 1
1.1 Declaration and assessment as a Priority Existing Chemical 1
1.2 Secondary notification 1
1.3 Objectives 2
1.4 New data 2
1.5 Background on use of TGIC in Australia 2
1.6 Report format 2
1.7 Peer review 3
2. APPLICANTS 4
3. CHEMICAL IDENTITY AND COMPOSITION 5
3.1 Chemical Identity 5
4. PHYSICAL AND CHEMICAL PROPERTIES 6
5. EVALUATION OF ANIMAL TOXICOLOGICAL DATA 7
5.1 Skin sensitisation 7
5.2 Combined 13-week toxicity and fertility study 8
5.3 Carcinogenicity 9
6. HUMAN HEALTH EFFECTS 12
6.1 Case reports 12
6.2 UK SWORD Notification System 13
7. HUMAN HEALTH HAZARD ASSESSMENT AND CLASSIFICATION 14
7.1 Skin sensitisation 14
7.2 Respiratory sensitisation 15
7.3 Repeated dose toxicity 16
7.4 Fertility 17
Triglycidylisocyanurate vii
7.5 Carcinogenicity 18
8. ENVIRONMENTAL ASSESSMENT 19
8.1 Environmental exposure 19
9. SUMMARY AND CONCLUSIONS 20
10. RECOMMENDATIONS 23
10.1 Classification and labelling 23
10.2 Further studies 24
10.3 Health Surveillance 25
10.4 Material Safety Data Sheets 25
10.5 Atmospheric monitoring and control of occupational exposure 25
11. SECONDARY NOTIFICATION 26
APPENDIX 1 - Sample Material Safety Data Sheet for Triglycidylisocyanurate 27
APPENDIX 2 - Recommendations for atmospheric monitoring and control of occupational
exposure (adapted from the Tgic-1 Report) 32
REFERENCES 37
LIST OF TABLES
Table 1 - Results of skin sensitisation study 8
Table 2 - Concentration limits and classifications for TGIC as an ingredient in
mixtures/preparations 24
Secondary Notification Assessment
viii
Acronyms and Abbreviations
CAS Chemical Abstracts Service
DNA deoxyribonucleic acid
EA Environment Australia
FEV1 forced expiratory volume in the first second
g gram
h hour
L litre
LC50 median lethal concentration
LD50 median lethal dose
LLNA local lymph node assay
mg milligram
MSDS Material Safety Data Sheet
NICNAS National Industrial Chemicals Notification and Assessment Scheme
NOAEL no observed adverse effect level
NOHSC National Occupational Health and Safety Commission
OECD Organisation for Economic Cooperation and Development
PD15 provocative dose causing 15% depression in FEV1
PEF peak expiratory flow
ppm parts per million
S.I. stimulation index
TGA Therapeutic Goods Administration
TGIC triglycidylisocyanurate
TWA time-weighted average
Triglycidylisocyanurate ix
Secondary Notification Assessment
x
1. Introduction
1.1 Declaration and assessment as a Priority Existing Chemical
The chemical triglycidylisocyanurate (CAS Number 2451-62-9), known as TGIC,
was declared a Priority Existing Chemical, under the Industrial Chemicals
Notification & Assessment) Act 1989 (the Act) on 5 November 1991. TGIC is used
in Australia as a cross-linking agent in powder coatings in the metal finishing
industry.
The reasons for the declaration were: (i) recent animal toxicity studies indicated a
potential for TGIC to cause genetic damage. The studies raised concern that TGIC
could be a human carcinogen and mutagen and could also have adverse
reproductive effects; and (ii) there were a significant number of workers exposed to
TGIC.
A comprehensive evaluation of the available toxicity and exposure data was
conducted and a full public report was published in April 1994 (NICNAS, 1994).
The assessment concluded that TGIC should be classified as toxic by oral and
inhalation routes, a skin sensitiser, mutagenic (category 2 mutagen) and capable of
causing serious eye damage. The report recommended an interim occupational
exposure limit as guidance for industry until a national exposure standard had been
set.
The report also detailed an extensive analysis of control measures to minimise
occupational exposure to TGIC. It concluded that TGIC was unlikely to cause
adverse human health effects if appropriate control measures (such as full
protective equipment) and atmospheric monitoring strategies were in place.
However, it noted that the long term health effects in workers exposed to TGIC
were difficult to predict in the absence of chronic data. The original assessment
report also concluded that TGIC was unlikely to present a risk to the public or the
environment.
Publication of the report was initially subject to delays pending an Administrative
Appeals Tribunal (AAT) decision regarding the classification of TGIC in the areas
of acute toxicity and mutagenicity. An application had been made to the AAT for
review of the Director's decision to refuse to vary the assessment report. All
decisions of the Director concerning classification were upheld by the AAT.
1.2 Secondary notification
In accordance with Section 62 of the Act, the publication of the full public report
revoked the declaration of TGIC as a Priority Existing Chemical. However, under
Section 64(2) of the Act, specific circumstances are prescribed where reassessment
(secondary notification) of a Priority Existing Chemical, may be warranted. These
circumstances include additional information as to the adverse health or
environmental effects of the chemical becoming available.
Triglycidylisocyanurate 1
In 1998, one company notified the Director of new information relating to the
respiratory sensitising potential of TGIC. As a consequence, notice was provided
in the Chemical Gazette of 5 January 1999 requiring reassessment of TGIC under
Section 65(2) of the Act. All persons who introduced TGIC into Australia, either
by import or manufacture, were required to apply for secondary notification, in
order for TGIC to proceed to assessment. Secondary notification was given by six
companies (see Section 2), who also supplied additional data.
1.3 Objectives
The objectives of this assessment were to review the new data made available since
the publication of the original assessment report (TGIC-1) and where appropriate,
revise the original assessment with regard to:
? the characterisation of the potential hazards of TGIC;
? the characterisation of the risks of adverse effects to workers, the general
public and the environment; and
? the recommendations to control exposures and/or reduce potential risks.
1.4 New data
New data supplied for this assessment were:
i. 13-week oral toxicity/fertility study in male rats
ii. 99-week oral carcinogenicity study in male rats
iii. Contact hypersensitivity study in guinea pigs
iv. 2 human case reports of skin and respiratory sensitisation
v. Biodegradability study
1.5 Background on use of TGIC in Australia
TGIC is a three-dimensional cross-linking or curing agent for powder coatings or
polyester resins. TGIC is not manufactured in Australia. The estimated amount of
TGIC imported as technical grade and as a component of powder coatings, is 100-
1000 tonnes per year. Imported technical grade TGIC is mixed with resin,
pigments, fillers and additives, at between four and ten percent by weight of the
final product. TGIC-containing powder coatings are sprayed onto metal objects,
using an electrostatic process, prior to curing in ovens.
1.6 Report format
For easy reference, the general format of this report follows that of TGIC-1. Only
sections where new data are available or revisions have been made are included in
this report. The following sections in the TGIC-1 report remain unaltered and the
reader will need to refer to the original report:
? Methods of detection and analysis
? Use
? Manufacture of TGIC powder coatings
Secondary Notification Assessment
2
? Occupational exposure
? Public health assessment
1.7 Peer review
During all stages of preparation, the report has been subject to internal peer review
by NICNAS, Environment Australia (EA) and the Therapeutic Goods
Administration (TGA). Associate Professor Malcolm Simm of the Unit of
Occupational & Environmental Health at Monash University reviewed the human
case reports relating to TGIC-induced occupational asthma.
Triglycidylisocyanurate 3
2. Applicants
Six companies applied for secondary notification assessment of the chemical. The
applicants supplied relevant information for this assessment, including animal
toxicity data, human health and environmental data. Under Section 36 of the Act,
the applicants were provided with a draft copy of the report for correction of errors
and variation of content.
Applications were received from:
Vantico Pty Limited
235 Settlement Road
Thomastown VIC 3074
Sumitomo Australia Limited
GPO Box 4241
Sydney NSW 2001
Dulux Australia
Powder & Industrial Coatings
51 Winterton Road
Clayton VIC 3168
Jotun Australia Pty Ltd
P.O. Box 105
Altona Nth. VIC 3025
Ameron Coatings
P.O. Box 356
Seven Hills NSW 2147
Interpon Powder Coatings
Akzo Nobel Pty. Limited
P.O. Box 26
Sunshine VIC 3020
Secondary Notification Assessment
4
3. Chemical Identity and
Composition
3.1 Chemical Identity
Triglycidylisocyanurate
Chemical Name:
2451-62-9
CAS No.:
1,3,5-Triglycidyl isocyanurate
Synonyms:
TGIC
1,3,5-Triazine-2,4,6(1H,3H,5H)-trione1,3,5-tris (oxiranylmethyl)-
1,3,5-Tris(oxiranylmethyl) 1,3,5-triazine-2,4,6(1H,3H,5H)-trione
Tris(2,3-epoxypropyl) isocyanurate
Araldite PT 810
Trade Names:
TEPIC
TK 10622
C12H15N3O6
Molecular
Formula:
Structural
Formula:
O
CH 2
O O
N
O O
CH 2 N N CH 2
O
297.3
Molecular
Weight:
Triglycidylisocyanurate 5
4. Physical and Chemical Properties
TGIC is manufactured and supplied as the technical grades TEPIC and Araldite
PT810 (also known as TK 10622). TGIC technical grades are white, granular
solids (at 20oC and 101.3 kPa) with no discernible odour. TEPIC has a melting
point range of 90 to 125oC, while Araldite PT 810 melts at 95oC. Densities are
1420 and 1460 kg/m3 respectively.
The water solubility and partition coefficient for TEPIC is 9 g/L at 25oC and log
Pow -0.8, respectively.
The reactivity of TGIC in the molten state is well characterised and includes
reactions with the following functional groups: primary and secondary amines,
carboxylic acids and anhydrides, thiols, phenols, and alcohols (at high
temperatures). Molten TGIC may also undergo autopolymerisation.
The conversion factors for TGIC (at 25oC) TGIC are:
1 mg/m3 = 0.082 ppm, and
?br>
= 12.18 mg/m3
? 1 ppm
Further details of the physical and chemical properties of TGIC are provided in
TGIC-1.
Secondary Notification Assessment
6
5. Evaluation of animal toxicological
data
Animal toxicological studies submitted for secondary notification have been
evaluated and are reported below. Full reporting of data evaluated in the original
assessment can be found in the TGIC-1 assessment report.
5.1 Skin sensitisation
Guinea pig maximization study
The skin sensitisation potential of TGIC (TK10622) was tested in male Albino
Dunkin Hartley guinea pigs (RCC, 1997). The study was conducted according to
OECD Guideline No. 406 `Skin Sensitisation' (1992).
Based on pretest data, 30% and 25% TGIC in corn oil were selected as the
maximum tolerated dose and highest non-irritant dose concentrations suitable for
the induction and challenge phase respectively. The test group (20 animals), were
subjected to two induction and challenge phases comprising of:
Induction I: Intradermal injections (0.1ml) of adjuvant and of 5% TGIC
(equivalent to 5 mg) in corn oil v/v (day 1)
Induction II: Topical application (approximately 0.3ml) of 30% TGIC
(equivalent to 90 mg) in corn oil v/v under occlusion for 48h (day
8)
Challenge I: Topical application (0.2ml) of 25% TGIC (equivalent to 50 mg)
(left flank) and corn oil only (right flank), under occlusion for 24h
(day 22)
Challenge II: Topical application (0.2ml) of 25% TGIC (right flank) and corn
oil only (left flank), under occlusion for 24h (day 29)
Guinea pigs in the control group (10 animals) were treated with vehicle only, and
were not subjected to a second challenge. All animals were pre-treated with 10%
Sodium-Lauryl-Sulfate (SLS) on day 7, to enhance sensitisation.
Clinical observations, viability/mortality, body weight and macroscopic findings
were recorded. Skin reactions were recorded at 24 and 48h after removing the
dressing following induction II, challenge I and challenge II. Erythema and
oedema were assessed using the Draize numerical grading system. The skin
reactions are summarised in Table 1. Only very slight erythema (Draize score 1)
was observed in some of the animals. No oedema was observed in any of the
animals. One animal in the control group died on day 7.
In a positive control group, 70% (7/10) of animals tested positive at challenge. The
positive control was a non-irritating concentration (25%) of alpha-
hexylcinnamaldehyde.
Triglycidylisocyanurate 7
In accordance with OECD Guideline No. 406 `Skin Sensitisation' (1992), TGIC
did not induce skin sensitisation in this study.
Table 1 - Results of skin sensitisation study
Number of animals presenting
with erythema**
Phase Treatment Group 24h* 48h*
Induction II Control 4/9 4/9
Test (30% TGIC) 10/20 10/20
Challenge I Control 0/9 0/9
Test (25% TGIC) 4/20 1/20
Challenge II Test (25% TGIC) 1/20 1/20
Positive control Alpha-hexylcinnamaldehyde 7/10 7/10
*Time (h) after treatment
**Each positive response received a Draize score of 1 for erythema.
Local Lymph Node Assay
The murine Local Lymph Node Assay (LLNA), which attributes a stimulation
index (S.I.) as a measure of lymphocyte stimulation derived from animal auricular
lymph nodes, has been proposed as a predictive test for the identification of
sensitising agents, and in particular as a predictor of skin sensitisation potential
(NIEHS, 1999).
Lymphocyte proliferation, induced in the lymph nodes of female BALB/c mice (3
per group, including control) exposed to 0.2% to 5% TGIC, (by topical application
to the dorsum of both ears), was assessed and a stimulation index (S.I.) determined
(Clottens et al, 1996). The LLNA is considered positive if a S.I. of at least 3 is
obtained. The maximal S.I. for TGIC was 2.0, with a 2-fold increase in the lymph
node cell number (LNC) and a 1.5 fold increase in lymph node weight. Taken
together, the data were considerably lower than for the positive control, which
provided an S.I. of 37 with a 6.4 fold increase in total LNC. Only an abstract for
this study was available. In addition, critical information as defined by NIEHS
(1999), was not reported.
5.2 Combined 13-week toxicity and fertility study
A combined oral 13-week toxicity and fertility study was conducted in Sprague
Dawley rats (CIT, 1995). The conduct of the study was similar to OECD
Guideline No. 408, however females were not exposed to TGIC at any time.
Toxicity study
Male rats (10 per group) were exposed to dose levels of 0, 10, 30 and 100 ppm ( 0,
0.73, 2.08, 7.32 mg/kg/day) TGIC for 94 days by dietary admixture (supplied ad
libitum). Examinations for ophthalmology (checked before treatment and at week
13 in control and 100 ppm group), haematology, blood biochemistry and urinalysis
(each performed at week 13) were made. Body weight gain and food consumption
were checked weekly. At the end of the treatment period the males were killed and
Secondary Notification Assessment
8
a pathological assessment including organ weight, macroscopic and microscopic
examination were made. Microscopic examination was performed in lungs, liver,
kidneys, prostate, seminal vesicles, testes and epididymis and lymph nodes
(mandibular and mesenteric) of all males.
No treatment-related clinical signs or mortality were observed at the 10 or 30 ppm
dose-level. At 100 ppm (7.32 mg/kg/day), treated animals had a consistently lower
body weight compared to controls, which was significant throughout most of the
treatment period. At the end of the study, treated animals had an 8% mean lower
body weight compared to controls. In addition, a significantly lower body weight
gain (-16%) over the first 6-week period was observed. Thereafter, the bodyweight
gain was similar to the controls. The only other effects observed were
hemosiderosis and/or congestion in the mesenteric lymph nodes of 4 animals at 100
ppm.
Fertility study
After the initial 9-week exposure period each male was placed overnight with 2
unexposed females until mating occurred or up to seven days maximum. On day
19 of pregnancy, the females of each group were allocated equally to two
subgroups (hysterectomy subgroup or delivery subgroup). Females in the
hysterectomy subgroup were killed on day 20, foetuses were removed by
Caesarean section and examined. Females in the delivery group were allowed to
deliver and rear their progeny until weaning. Between day 22 and 25 post-partum,
the females and pups were killed and examined. Females received only untreated
diet ad libitum throughout the study.
No clinical signs, unscheduled mortality, abortions, differences in body weight or
relevant macroscopic findings (at necropsy) were noted in the maternal animals. In
the litter of the hysterectomy subgroup, there were no differences in corpora lutea
and implantation sites, post-implantation losses, live foetuses and fatal external
abnormalities. In the litter of the delivery subgroup, there were no differences in
the litter size, pup weight and viability, clinical signs or pup development.
No treatment-related male infertility, as measured by the mating and fertility
indices was noted.
A treatment-related decrease in mean number of spermatozoa was noted in males
treated with 30 and 100 ppm TGIC, however, further independent statistical
analysis of the data (ANOVA) revealed that this was not statistically significant
when compared to controls (p>0.5). Mean spermatozoa viability was unaffected.
Under the conditions of this study, the no observed adverse effect level (NOAEL)
is 7.32 mg/kg/day (100 ppm).
5.3 Carcinogenicity
The carcinogenic potential of TGIC was examined in 50 male Sprague-Dawley rats
per dose level over a 99-week exposure (CIT, 1999). The study was conducted
according to OECD Guideline No. 451 (OECD, 1981), with the exception that
female rodents were not included in the study.
Animals were given by dietary admixture either 0, 10, 30, 100 or 300 ppm TGIC
(achieved doses of 0, 0.43, 1.30, 4.36 and 13.6 mg/kg/day, respectively). In
Triglycidylisocyanurate 9
addition, a satellite group (10 males per dose level) were exposed for 26 weeks to
0, 100, and 300 ppm TGIC.
Microscopic examination was performed in all tissues, macroscopic lesions and
palpable masses from control and high-dose (300 ppm) animals at the end of the
treatment period in the principal and satellite groups. Additionally, similar
examination of the intermediate dosed (100 ppm) animals of the principal study
group was conducted at the end of the treatment period.
a) Principal Group
Due to the high level of mortality and marked signs of toxicity at 300 ppm,
treatment was stopped at week 63 for this group, and the animals were sacrificed.
The only positive trend for neoplastic lesions was pituitary adenomas, however this
was mainly due to a higher incidence at 30 ppm.
At 100 ppm, terminal body weight was lower (-9%) as well as mean food
consumption in treated animals compared to controls, however the differences
were not statistically significant. A slight increase in hepatocellular adenoma (6/50
vs. 4/50 for controls) and carcinomas (3/50 vs. 0/50 for controls) was noted,
however the incidence was not dose-related and was within the range of historical
controls.
Treatment-related effects observed in the 300 ppm group include:
? Poor clinical condition (including round back, piloerection and emaciation)
was noted as early as week 34.
? At week 52, a higher mean neutrophil count (+41%) and mean monocyte
count (+50%) was noted, while at week 63, a lower lymphocyte count
(-33%), and a lower mean total leukocyte count (-23%) at week 63 (P<0.01)
was noted.
? A significantly higher incidence of mastocytosis in the mesenteric lymph
nodes, hemosiderosis, splenic lymphoid depletion and sinusal haemorrhage.
? A high incidence of dilated lumen in the duodenum, jejunum and ileum. In
addition, a higher incidence of hyposecretion and small tubulo-alveolar units
in the prostate.
? Onset of mortality occurred significantly earlier (week 45).
? At 52 weeks, the survival rate was lower (56% in 300 ppm group compared
to 90% in controls.)
? A marked decrease in body weight gain persisted throughout the study
period, and by week 62 was 68% lower (p<0.01) than controls for the same
period.
? A consistently lower mean food consumption, which was statistically
significant.
b) Satellite Toxicity Group
No treatment-related clinical signs or mortality were observed in the satellite
toxicity group, and no adverse effects were observed at 100 ppm. High dose (300
ppm) treated animals revealed the following changes:
Secondary Notification Assessment
10
? Body weight gain was markedly lower (-77%) than controls during the initial
8-week treatment period and less marked by the end of the 16-week treatment
period (-43%).
? Significantly decreased mean food consumption level throughout the 16-week
treatment period.
? Slightly lower mean total leukocyte count (-35%, p<0.01), and a slightly higher
thrombocyte count (+19%, p<0.05).
? Slightly lower mean total protein level (attributable to a slightly lower globulin
level) was most marked at week 27 (-9%) when compared to controls.
? Increased relative mesenteric lymph nodes (88%, p<0.01), associated with
hemosiderosis, plasmacytosis, mastocytosis and sinusal haemorrhages.
Statistical significance as determined by the Kruskal-Wallis test, was attributed
to the mesenteric lymph node data alone.
? Lower absolute weights of thymus (-24%, p>0.05) and spleen (-37%, p>0.05),
associated with lymphoid depletion.
? Lower absolute weights of prostate (-27%, p>0.05), and seminal vesicles
(-36%, p>0.05), associated with moderate hyposecretion.
Conclusion
In conclusion, there were no adverse effects in animals treated up to 100 ppm.
TGIC failed to induce an increase in tumours in a dose-dependent manner in males,
at doses up to 100 ppm.
At the highest dose (300 ppm), the principal effects were decrease in body weight,
mastocytosis in the lymph nodes and depletion of the spleen lymphoid cells in both
study groups. Increased mortality resulted in the group being sacrificed at week
63. The authors concluded that marked mastocytosis in the mesenteric lymph
node, together with sinusal haemorrhage, indicate that a histamine-related
hypotension might have been the cause of death in this group.
The NOAEL for non-neoplastic effects in this study is 100 ppm (4.36 mg/kg/day).
Triglycidylisocyanurate 11
6. Human Health Effects
6.1 Case reports
Two recent case reports were available for assessment.
The first published case report (Piirila et al., 1997) describes a male spray painter
exposed to powder paints containing TGIC (4% v/v), for periods extending 5 ?8h
daily over 7 years. The worker suffered from eczema on his hands, face and body,
symptoms of dyspnoea, particularly during and after workdays, and from
dyspnoea, coughing and wheezing at night and during exercise. The authors state
that `no atopic tendency had been verified' prior to working as a spray painter.
Protective clothing and a motorised breathing protector were used during painting.
TGIC-induced contact dermatitis was diagnosed, following positive patch testing
with polyester paint containing 10% and 3.2% TGIC, or 1%, 0.32% or 0.1% TGIC
in petroleum.
Skin prick tests to TGIC and tests for IgE specific to TGIC were negative, however
total serum IgE was elevated. Peak flow follow-up revealed a regular 20% diurnal
variation, reducing to less than 10% following a 3 month budesonide treatment,
and significant bronchodilatation responses of 17 ?20%. The lactose-control
challenge test was negative. Moderate bronchial hypersensitivity (PD15 0.33 mg),
as measured by the provocative dose causing 15% depression in FEV1, was
observed following a histamine challenge test. A challenge test with paint
containing 4% TGIC, induced a 15% fall in peak expiratory flow (PEF) 30 minutes
after exposure, together with tightness in the chest. Additionally, there was a late
fall of 23% in the forced expiratory volume in the first second (FEV1) and 17% in
PEF, at 11h and 16h after challenge, respectively.
When challenged with 4% TGIC containing lactose (1:1), an immediate 17% fall in
PEF (within 15 minutes) was observed. In addition, a late 16% fall in PEF and
19% in FEV1 (both 6h post exposure), and a 16% fall in PEF and 15% in FEV1
(both 13h post exposure) was observed. When the histamine challenge test was
repeated post challenge, moderate bronchial hyper-reactivity was observed, with
the PD15 significantly lower.
The second published case report (Meuleman et al., 1999) describes a spray painter
(without pre-existing atopic disease) exposed to polyester powder pigments,
containing 1?% w/w TGIC, over a three-year period. Although he wore a
protective mask, but not protective gloves, he developed sustained erythematous,
papular, and plaque-like lesions on his arms and legs, as well as the axillae and
upper part of the back. Respiratory symptoms including, rhinitis, dyspnoea, cough
and wheezing, appeared shortly after the skin lesions. A decrease in symptoms
during weekends provided a clear association with his occupational activities.
Positive patch test results, to TGIC (0.5% and 5% in petroleum) and one of the
pigment powder samples, were observed 2 to 3 days post exposure.
Secondary Notification Assessment
12
Specific bronchial provocation tests involving inhalation of aerosolised 0.05%
TGIC (in lactose) induced a progressive decrease in FEV1 to ?2% by 6h. The
following day, a second challenge test using 0.1% TGIC (in lactose) was mounted,
the response was clearly positive with a maximal decrease in FEV1 of ?1% at 4 h
after exposure. The worker experienced coughing, wheezing, dyspnoea and itching
during the night following the provocation test. Skin prick tests with TGIC were
inconclusive. Serum IgE levels were measured before the bronchial provocation
tests and found to be elevated.
Taken together, the data provide evidence of allergic contact dermatitis and
occupational asthma as a result of exposure to TGIC.
6.2 UK SWORD Notification System
The UK Surveillance of Work-Related & Occupational Respiratory Disease
(SWORD) is a national scheme for the reporting of new cases of occupational
respiratory diseases (including asthma) by thoracic and occupational physicians.
Since the Scheme began in 1989, eleven cases of asthma have been attributed to
TGIC exposure (approximately 2 cases per year from 1994-2000) (McDonald JC
(2000), personal communication).
Triglycidylisocyanurate 13
7. Human Health Hazard Assessment
and Classification
This section integrates data on animal toxicity and human health effects in order to
characterise potential human health hazards from exposure to TGIC and classify
these hazards. The classification criteria used throughout are the NOHSC Approved
Criteria for Classifying Hazardous Substances (the Approved Criteria) (NOHSC,
1999).
Only those toxicity endpoints where new data were available for this assessment
are considered. The hazard assessment of these endpoints takes into account the
new data (described and evaluated in Section 6) and relevant data from the TGIC-1
report.
7.1 Skin sensitisation
In TGIC-1, animal and human health data concerning the skin sensitisation
potential of TGIC were available. A summary of the data is as follows:
Animal studies
In 2 studies, the skin sensitisation potential of TGIC was assessed in male and
female guinea pigs (Ciba-Geigy Ltd, 1988, Safepharm Laboratories Ltd,1988). In
the studies, a two-stage induction process was followed by 1 or 2 challenge phases.
The duration of exposure to TGIC during the challenge phase was limited to 24h.
The challenge phase concentrations of TGIC were 20 mg (Ciba Geigy Ltd, 1988a)
or 50-100 mg (Safepharm Laboratories Ltd, 1988). TGIC tested positive for
sensitisation in both studies.
Human studies
Three case studies reported TGIC-induced contact dermatitis. In each case the
worker had been exposed to TGIC or TGIC powder coatings, and complained of
dermatitis. The workers were patch-tested with TGIC and the results were
positive. ICI Dulux also provided a summary of the health status of employees at
an Australian powder coating manufacturing plant, whereby, two employees had
allergic dermatitis (confirmed positive by TGIC patch-test analysis).
New animal and human data, concerning the skin sensitisation potential of TGIC
are summarised as follows:
Animal studies
A negative study was reported, examining the skin sensitisation potential of TGIC
in a group of 20 male guinea pigs. A murine LLNA was negative however only an
abstract was available for assessment, and essential information was not reported.
Secondary Notification Assessment
14
Human studies
Two recently published case reports were available for this assessment. In both
studies, spray painters using TGIC powder coatings for extended periods of time
reported dermatitis. Clinical examination revealed eczema in both workers, and
returned positive patch-tests to TGIC and TGIC powder coatings.
In summary, there are now 5 human case reports of skin sensitisation, 2 positive
and 1 negative guinea pig maximisastion studies and 1 negative murine LLNA
(abstract only). The recent sensitisation study in guinea pigs was negative, which
is in contrast with the findings of 2 similar studies reported in TGIC-1. Although
there are small differences in dose at induction and challenge in these animal
studies, they are unlikely to account for the differences in results. In fact, the
methodology adopted by Safepharm Laboratories Ltd (1991) is the same as the
latest study (Ciba-Geigy Ltd, 1997), with the exception of the slightly lower doses
at the second induction (90 mg in the Ciba study c.f. 100-150 mg in the Safepharm
study).
Classification status
Based upon available animal and human data, TGIC satisfies the Approved Criteria
for classification as a substance causing sensitisation by skin contact.
7.2 Respiratory sensitisation
TGIC-1 reported that ICI Dulux had provided a summary of the health status of
employees at an Australian powder coatings plant. In 1991, two separate incidents
of TGIC-aggravated intrinsic asthma were reported (no further details provided).
Shortly after, twenty-eight employees were given medical examinations, and
respiratory irritation was present or reported in five employees. No TGIC exposure
monitoring data was provided (this data was not used for classification because of
the lack of reporting detail).
New respiratory sensitisation data is limited to two human case reports (Piirila et
al., 1997; Meuleman et al., 1999), each demonstrating positive bronchial
provocation test data. The studies report on two spray painters, who, after working
with TGIC powder coatings (1-7% w/w) for extended periods of time, reported
respiratory symptoms including rhinitis, dyspnoea, cough and wheeze.
In both cases, occupational asthma was diagnosed following bronchial provocation
tests, involving challenges to aerosolised TGIC. The time taken to reach a greater
than 20% reduction in FEV1 was considerably longer in the Piirila report (11h vs
6h) and the concentration of TGIC used during bronchial provication was much
higher (4% vs 0.05%). These clinical differences may reflect patient-specific
differences and are considered not to weaken the evidence for the positive causal
relationship between TGIC and occupational asthma. Skin prick tests to
unconjugated TGIC however, were negative in one (Piirila et al., 1997), and
inconclusive in the other (Meuleman et al., 1999).
As there are currently no known published epidemiological studies, rates of
occupational asthma in TGIC-exposed populations remain unclear. However,
under the UK SWORD notification system, eleven cases of asthma have been
attributed to TGIC since 1989.
Triglycidylisocyanurate 15
Classification status
The classification system prescribed in the Approved Criteria states that a chemical
meets these criteria if there is evidence that the substance can induce specific
respiratory hypersensitivity. As is the case with TGIC, this evidence is usually
human data. In considering the human evidence for TGIC, the explanatory notes
regarding the use of R42 have been taken into account as follows:
? Two case reports show positive bronchial challenge on exposure to TGIC and
thus provide sufficient evidence for classification on their own. (paragraph
4.63 of the Approved Criteria)
? In the two case studies, exposure to TGIC resulted in respiratory
hypersensitivity, that is, the clinical condition of asthma (in addition to
dyspnoea and rhinitis). There is no data to show that the asthma elicited by
TGIC is a result of respiratory irritation in bronchial hyper-reactive individuals.
There was no evidence that the asthma was caused by irritation in hyper-
reactive individuals. Similar to other low molecular weight substances known
to cause respiratory sensitisation, no immunological mechanism has been
demonstrated. (paragraphs 4.59 and 4.64)
? Both case studies provide relevant clinical history (medical and occupational
information) to support a relationship between exposure to TGIC and the
development of respiratory hypersensitivity. Lung function tests, including
serial peak flow measurements and assays for bronchial hyper-responsiveness
to histamine, provide further evidence. (paragraph 4.62)
Supporting evidence
? Case reports do not give an indication of the incidence of respiratory
sensitisation amongst TGIC workers and no epidemiological studies have been
conducted. Because of the other known adverse health effects of TGIC, the
wearing of personal protective equipment (including respiratory protection) is
recommended by manufacturers and distributors of TGIC and TGIC products
and is common practice in workplaces. Therefore, the number of cases
reported as a function of population size would be expected to be low.
However, in addition to the 2 case studied discussed in the report in detail,
under the UK SWORD notification scheme 11 cases of occupational asthma
have been attributed to TGIC exposure. (paragraph 4.60)
? TGIC is structurally related to isocyanates and has reactive epoxide side
groups, which suggests TGIC may have the potential for sensitisation.
(paragraph 4.61)
7.3 Repeated dose toxicity
No long-term repeated dose studies were available for assessment for TGIC-1.
Only short-term repeated dose (5 or 7 day) studies in rodents were available.
Results of these short-term studies are described below.
Male rats were administered 0, 54 or 216 mg/kg/day TGIC, and females
administered 0, 43 and 172 mg/kg/day by gavage for 7 days (Shell Research Ltd,
1971). No abnormal clinical signs or symptoms were observed. Minor
Secondary Notification Assessment
16
cytoplasmic vacuolation of distal convoluted tubule epithelia were observed in
males in the low dose group. In the high dose groups, renal tubular damage, and
haemorrhagic and degenerative changes of the gastric and duodenal mucosa were
observed.
Male mice were administered 0, 10, 40 or 140 mg/m3 TGIC for five days
(Safepharm Laboratories Ltd, 1991). No adverse effects were observed in mice
exposed to 10 mg/m3 TGIC. However, adverse clinical signs, increased
bodyweight losses and higher mortality occurred at inhaled dose levels of 40 and
140 mg/m3 TGIC.
Male mice were exposed nose-only to 7.8 mg/m3 or orally to 115 mg/kg/day,
TGIC, for five days (Safepharm Laboratories Ltd, 1992). No adverse clinical signs
or deaths were observed and bodyweight gain was unaffected.
In this report, a 13-week toxicity study was assessed (CIT, 1995). Exposure to
0,10, 30 or 100 ppm (0, 0.72, 2.08 or 7.32 mg/kg/day) TGIC by dietary admixture
in male rats was well tolerated. At the highest dose, treated animals exhibited a
statistically significant lower body weight, the only effect observed.
Additionally, data on the non-neoplastic effects of TGIC can be obtained from the
new 99-week carcinogenicity study in male rats exposed to 0, 10, 30, 100 or 300
ppm (0, 0.43, 1.30 or 4.36 and 13.6 mg/kg/day) (CIT, 1999). Principal effects seen
at the highest dose studied (300 ppm) included, decrease in body weight,
mastocytosis in the lymph nodes and depletion of the spleen lymphoid cells.
However, increased mortality within the group meant these animals were sacrificed
at week 63. There were no treatment-related non-neoplastic changes observed in
lower dosed groups.
Classification status
Reduced body weight was observed in the 13-week toxicity study at 100 ppm (7.32
mg/kg/day) and in a carcinogenicity study (CIT, 1999) a rapid onset of mortality
and other severe effects were observed at 300 ppm (13.6 mg/kg/day) TGIC. TGIC
is classified as `Harmful' for severe effects after repeated or prolonged exposure.
7.4 Fertility
While no standard fertility studies were available for assessment for TGIC-1,
genotoxicity studies indicated that TGIC induced chromosomal aberrations and
cytotoxicity in mouse spermatogonia and reduced fertility in males in a dominant
lethal test. These findings raised the possibility of reproductive effects of TGIC.
Studies in male mice included exposure of TGIC by nose-only inhalation
(Safepharm Laboratories Ltd, 1992), and oral administration (Ciba-Geigy Ltd,
1986; Hazleton Laboratories America Inc, 1989; and Hazleton Microtest, 1991).
The nose-only inhalation study established that exposure of mice to 7.8 mg/m3
TGIC (only dose tested) over 5 days did not induce chromosomal aberrations or
cytotoxicity in spermatogonial cells, or adverse clinical effects. In the oral studies,
chromosomal aberrations were seen at the lowest dose tested, 28.5 mg/kg/day and
cytotoxicity at 57.5 mg/kg/day and above.
In a dominant lethal study in which TGIC did not induce mutations, reduced
fertility was observed in males at the highest dose, 50 mg/m3. The reductions in
Triglycidylisocyanurate 17
fertility were consistent with effects on mature sperm, maturing spermatids and
Type-B spermatogonia.
In this report, a combined, 13-week fertility study was assessed (CIT 1995).
Exposure to 0, 10, 30 or 100 ppm (0, 0.72, 2.08 or 7.32 mg/kg/day) TGIC by
dietary admixture in male rats was well tolerated. A slight treatment-related
decrease in the mean number of spermatozoa was noted at the 30 and 100 ppm
doses; however, this was not statistically significant when compared to controls.
There was no treatment-related infertility in males or changes in embryonic and
pup development. However, females were not exposed in this study. The
NOAEL is considered to be 7.32 mg/kg/d.
Classification status
The potential effects of chromosomal damage in spermatogonia in mice were not
demonstrated as infertility in male rats, or developmental effects when males were
exposed to repeated, lower doses of TGIC. The effects of TGIC on female fertility
and developmental effects as a result of maternal exposure to TGIC have not been
investigated.
There is insufficient data to classify TGIC with respect to effects on fertility or
developmental toxicity.
7.5 Carcinogenicity
Although no carcinogenicity studies were available for assessment for TGIC-1, the
mutagenic potential of TGIC was assessed, and categorised as a `Category 2
mutagen' accordingly. TGIC was positive in a number of short-term in vivo and in
vitro genotoxicity studies and shown to covalently bind to DNA. The results raise
the question of potential carcinogenic effects of TGIC.
In this report, the carcinogenic potential of TGIC was examined in male Sprague-
Dawley rats over a 99-week exposure period. Animals were given by dietary
admixture either 0, 10, 30, 100 or 300 ppm (0, 0.43, 1.30, 4.36 and 13.6
mg/kg/day) TGIC. The 300 ppm dosed group was sacrificed at week 63 due to
high mortality and adverse clinical signs.
The NOAEL for non-neoplastic effects is 4.36 mg/kg/d. This NOAEL is
approximately equivalent to an inhalation exposure level of 23.2 mg/m3 over 6-
hours (assuming a rat body weight of 0.215 kg and inhalation rate of 0.161 m3/d).
TGIC failed to induce an increase in the incidence of tumours at doses up to 100
ppm in male rats.
Non-neoplastic effects were not observed at 100 ppm and females were not
investigated. Notwithstanding the positive mutagenicity potential of TGIC
reported in TGIC-1, additional data is required before classification for the
carcinogenic potential of TGIC can be made.
Classification status
There is insufficient data to classify the carcinogenic potential of TGIC.
Secondary Notification Assessment
18
8. Environmental Assessment
8.1 Environmental exposure
As highlighted in the initial assessment of TGIC, the chemical is an epoxide where
any residues released to the environment are expected to be rapidly degraded,
either through microbal action or abiotic hydrolysis. In the aquatic environment,
persistence is expected to be limited (half-life expected to be less than 10 days in
fresh water) with hydrolysis proceeding more rapidly in the marine environment.
Studies provided showed TGIC is not readily biodegradable using the modified
Sturm test, with 48% degradation from a solution containing TGIC at 20 ppm after
28 days. However, in a modified Zahn-Wellens test, the compound was inherently
degradable.
Since the original TGIC-1 assessment, the ready biodegradability of TGIC has
been further assessed in a CO2 evolution (28 day Modified Sturm) Test in
accordance with EEC Directive 92/69 and OECD Guideline No. 301 B (Grutzner,
1997). Exposure was prolonged to 43 days because the chemical showed no sign
of biodegradation by exposure day 28. The inoculum was activated sludge from a
domestic waste water treatment plant. Concentrations in the test solution appeared
to be around 33 ppm, with 100 mg of TGIC added to test flasks containing 3 litres
of medium. Only one concentration was tested for biodegradability. To determine
whether the compound had any toxic effect on the microorganisms, a toxicity
control was established where 51 mg of TGIC was added along with 39 mg of the
reference compound, aniline, to a flask containing 3 litres of test medium, giving a
concentration of around 17 ppm. This concentration was around half of that used
to test biodegradability, and the reason for this is not made clear in the study. The
outcomes of this study showed TGIC to be nonbiodegradable and nondegradable
(in the absence of activated sludge) over the 43 days exposure with zero
degradation recorded. Likewise, the abiotic control containing TGIC and sterile
test medium showed no abiotic degradation. While the toxicity control showed no
inhibitory effect (around 44% degraded after 28 days, although it is not clear
whether this was solely due to the aniline), the effective concentration of TGIC was
around half that used in the degradation strudy. However, as an earlier test showed
48% degradation from a solution containing TGIC at 20 ppm after 28 days (see
above), an inhibitory effect at 33 ppm must be considered.
Triglycidylisocyanurate 19
9. Summary and Conclusions
Triglycidylisocyanurate (TGIC) is a triepoxy compound used as a cross-linking or
curing agent for polyester resins. In Australia, TGIC is only imported, and is used
principally as an ingredient in polyester powder coatings in the metal finishing
industry. TGIC is either imported as technical grade TGIC for the manufacture of
powder coatings or imported in powder coatings formulated overseas. An
electrostatic process is used to spray powder coatings onto metal objects, such as
steel furniture, car parts, metal fencing, window and door frames.
TGIC was assessed by NICNAS as a priority existing chemical in 1994. The
availability of significant new data has led the chemical to be reassessed
(secondary notification). New data supplied for secondary notification assessment
included contact hypersensitivity, repeated dose toxicity, fertility and
carcinogenicity animal data, human health effects data and an environmental
biodegradability study.
The new data was assessed and considered together with the health assessment data
in original TGIC report. The major impact of the new data relates to respiratory
sensitisation, and effects due to prolonged exposure. The data, considered as a
whole, are summarised below.
The human health effects reported in the literature are skin and respiratory
sensitisation. Several case reports of allergic dermatitis and occupational asthma in
workers exposed to TGIC or TGIC powder coatings have been published. Patch
tests with TGIC, to confirm skin sensitisation of these workers, were positive.
Positive bronchial challenge tests confirmed respiratory sensitisation. Other health
effects reported amongst workers in Australia include nasal, eye and throat
irritation, skin rash and nose bleeds.
In animals, TGIC is acutely toxic by the oral and inhalational routes but has low
acute dermal toxicity. TGIC causes serious eye effects, is a skin sensitiser and is
not a skin irritant. The major effects in short-term repeated dose studies were at the
site of application, including renal, lung and gastric/duodenal damage.
TGIC is genotoxic, in vitro and in vivo in mice. TGIC induced chromosomal
aberrations in mouse spermatogonia following oral administration. TGIC was also
positive in in vivo nucleus anomaly assays and induced sister chromatid exchanges
in a number of in vitro genotoxicity studies. The evidence for induction of
dominant lethal mutations by TGIC is equivocal. TGIC was shown to bind to rat
liver DNA in vivo following oral and intraperitoneal administration. Genotoxicity
studies indicated that inhalation of TGIC resulted in cytotoxicity and chromosomal
aberrations in spermatogonial cells of mice. In a dominant lethal study, TGIC
showed reduced fertility following inhalation in some but not all cases studied.
This data raised concerns that there may be a risk of reproductive effects from
exposure to TGIC. In a recent study, effects on male fertility and developmental
effects were not observed when male rats were exposed to TGIC up to the
maximum dose tested (100 ppm). However, even at the highest dose, apart from a
slightly lower body weight gain, no other effects were observed. Effects on female
Secondary Notification Assessment
20
fertility and developmental effects as a result of maternal exposure, have not been
tested.
The only available chronic data indicate that the NOAEL in male rats is 100 ppm,
with severe effects occurring at 300 ppm. TGIC did not induce an increase in
tumours up to 100 ppm in these animals. Principal effects at 300 ppm included
decrease in body weight, mastocytosis in the lymph nodes, depletion of the spleen
lymphoid cells and death. Females were not tested.
The sources of occupational exposure during manufacture of TGIC powder
coatings include weighing out of TGIC, filling hoppers, mixing, transfer of powder
mixes in open vessels, extrusion, milling, bagging, cleaning up spills, and cleaning
equipment. Sources of occupational exposure during use of TGIC powder coatings
include filling hoppers, spraying, cleaning up spills, cleaning equipment and
cleaning spray booths.
Based upon all the available data, and in accordance with NOHSC Approved
Criteria, TGIC should be classified as:
? toxic by inhalation and if swallowed.
? may cause sensitisation by inhalation.
? risk of serious damage to eyes.
? may cause sensitisation by skin contact.
? `harmful' for severe effects after repeated or prolonged exposure.
? may cause heritable genetic damage (Category 2 mutagen).
As a result of the original toxicity assessment, TGIC-1 noted that there were a
number of critical data gaps and recommended studies to examine the chronic
toxicity, carcinogenicity and reproductive toxicity of TGIC.
The impact of new data on the recommendations for further toxicity testing, as
outlined in TGIC-1, is summarised accordingly:
? The oral carcinogenicity in male rats provides some evidence for lack of
tumour development (up to 4.36 mg/kg/day). However, females were not
tested. Additional data is required before classification for the carcinogenic
potential of TGIC can be made.
? The combined 13-week toxicity/fertility study provides some information on
reproductive toxicity. The study established a NOAEL (7.32 mg/kg/day) for
male rats (including fertility), reporting no treatment-related infertility in
males or change in embryonic and pup development following exposure of
males to TGIC. However, females were not exposed to TGIC and potential
effects on the next generation were not studied. Therefore, the study did not
adequately address potential effects on the offspring (as a result of male or
female reproductive toxicity) or female fertility.
At the time of writing the TGIC-1 report, no national occupational exposure
standard for TGIC had been adopted. TGIC-1 acknowledged that a national
occupational exposure standard should be predicated on chronic data, but in its
absence concluded the genotoxic potential of TGIC as the critical determinant in
establishing an occupational exposure standard. Accordingly, TGIC-1
Triglycidylisocyanurate 21
recommended that NOHSC set an exposure standard. Subsequently, a time-
weighted average exposure standard for TGIC of 0.08 mg/m3 was set by NOHSC
(adopted December, 1995). The exposure standard was based on the Safepharm 6-
hour inhalation study (Safepharm Laboratories Ltd , 1992), where the lowest no
effect level was 7.8 mg/m3.
The NOAEL for non-neoplastic effects in a recent 99-week oral study in male rats
was 100 ppm (4.36 mg/kg/d). This NOAEL is approximately equivalent to a 6-
hour exposure level of 23 mg/m3 (based on a rat body weight of 215 g and an
inhalation rate of 0.161 m3/d). Based on the chronic data, review of the
occupational exposure standard is not warranted.
The new data demonstrates that TGIC is a respiratory sensitiser and like all
sensitisers, exposure levels should be kept to a minimum. This is consistent with
the conclusion in TGIC-1; that is, TGIC is a sensitiser and is genotoxic, and
therefore, occupational exposure levels should be maintained at the lowest levels
practicable. Experience has shown that exposure levels of 0.08 mg/m3 can be
achieved and maintained in powder coating manufacturing plants and spray paint
workshops.
The conclusions of the earlier report still stand, that TGIC is unlikely to cause
adverse human health effects if appropriate control measures (including personal
protective equipment where necessary), safe work practices and atmospheric
monitoring and health surveillance strategies (when necessary) are implemented.
Additional biodegradability data for TGIC confirms the findings of the TGIC-1
assessment, that is, TGIC is not expected to accumulate in soil or sediment because
of high mobility and limited persistence. Persistence in the aquatic environment is
also expected to be limited. The reactivity of TGIC precludes any possibility of
bioaccumulation.
Finally, TGIC is unlikely to present a risk to the public or the environment under
the current use conditions.
Secondary Notification Assessment
22
10. Recommendations
10.1 Classification and labelling
In the TGIC-1 report, TGIC was classified as toxic by oral and inhalation routes,
capable of causing serious eye damage, a skin sensitiser, and a Category 2
mutagen, in accordance with the health effects criteria detailed in the National
Commission's Approved Criteria for Classifying Harzardous Substances (NOHSC,
1999).
This secondary notification assessment has shown no data to change TGIC-1
recommendations and in addition, new data indicate that TGIC should also be
classified as a respiratory sensitiser and `harmful' for severe effects following
repeated exposure.
Based on the classification of its health effects and in accordance with the
Approved Criteria (NOHSC, 1999), TGIC is considered to be a hazardous
substance.
The complete requirements for the labelling of hazardous substances are detailed in
the National Code of Practice for the Labelling of Workplace Hazardous
Substances (NOHSC, 1994a). The following risk phrases and appropriate safety
phrases apply to the present report and have been determined by application of the
criteria given in the labelling guidance note and will ensure that the labelling
requirements of the National Commission's National Model Regulations for the
Control of Workplace Hazardous Substances (NOHSC, 1994b) have been met.
Risk phrases
? Toxic by inhalation and if swallowed.
R23/25
? Risk of serious damage to eyes.
R41
? May cause sensitisation by inhalation.
R42
? May cause sensitisation by skin contact.
R43
? May cause heritable genetic damage.
R46
? Danger of serious damage to health by prolonged exposure if
R48/22
swallowed.
Appropriate safety phrases include:
? Do not breathe dust.
S22
? Avoid contact with skin and eyes.
S24/25
? In case of contact with eyes, rinse immediately with plenty of
S26
water and contact a doctor or Poisons Information Centre.
? After contact with skin, wash immediately with plenty
S28
of...[material to be specified by manufacturer].
Triglycidylisocyanurate 23
? Wear suitable protective clothing.
S36
? Wear suitable gloves.
S37
? In case of insufficient ventilation wear suitable respiratory
S38
equipment.
? Wear eye/face protection.
S39
? If you feel unwell contact a doctor or Poisons Information Centre
S44
(show label where possible).
Where TGIC is an ingredient in a mixture/preparation, as in powder coatings, the
following concentration limits apply:
Table 2 - Concentration limits and classifications for TGIC as an ingredient in
mixtures/preparations
Concentration limit Classification
25% C Toxic; R23/25, R48/22, R41, R42/43, R46
10% C < 25% Harmful; R20/22, R41, R42/43, R46, R48/22
5% C < 10% Harmful; R20/22, R41, R42/43, R46
3% C < 5% Harmful; R20/22, R42/43, R36, R46
1% C < 3% Harmful; R42/43, R36, R46
0.5% C < 1% Harmful; R36, R46
0.1% C < 0.5% Harmful; R46
C < 0.1% Not a hazardous substance
C concentration of TGIC in powder coatings
The above data represent classifications for preparations containing TGIC at
concentrations between the ranges shown. However, should there be other
hazardous ingredients present in the preparation, the overall classification for the
preparation needs to be determined. In this case users should refer to the National
Commission's Approved Criteria for Classifying Hazardous Substances (NOHSC,
1999) for further guidance.
10.2 Further studies
The data gaps and recommended further studies noted in TGIC-1 still apply and are
as follows:
? Chronic toxicity and carcinogenicity data (such as a combined chronic
inhalation/carconogenicity study in a mammalian species).
? Reproductive and developmental toxicity (such as a multigeneration
reproduction study).
Secondary Notification Assessment
24
10.3 Health Surveillance
A workplace assessment is required by the National Model Regulations for the
Control of Workplace Hazardous Substances (NOHSC, 1994b) of the risks to
health consequent upon exposure to a hazardous substance. According to the
NOHSC Guidelines for Health Surveillance (NOHSC, 1995) an employer must
consider if use of a hazardous substance in the workplace presents a significant risk
to health and, if so, establish an appropriate health surveillance program.
As TGIC is a respiratory and skin sensitiser, particular attention should be paid to
worker exposure via skin contact and inhalation of TGIC powder coatings. A
medical practitioner appointed by the employer can assist in deciding if the health
surveillance is required, and if so, design an appropriate a program.
10.4 Material Safety Data Sheets
The NOHSC National Code of Practice for the Preparation of Material Safety
Data Sheets (NOHSC, 1994c) provides guidance for the preparation of MSDS.
It is recommended that suppliers amend their MSDS, taking into account the new
health effects data and the classification and cut-off levels recommended in Section
11.1. In particular, the MSDS should reflect the new information on chronic health
effects and respiratory sensitisation. Some suggested wording is provided in the
sample MSDS at Appendix 1.
10.5 Atmospheric monitoring and control of occupational exposure
Recommendations in TGIC-1 in relation to atmospheric monitoring and
occupational control measures are considered to be appropriate. For information, a
copy of the relevant sections from TGIC-1 is provided in Appendix 2.
Triglycidylisocyanurate 25
11. Secondary Notification
Under Section 65 of the Act, the secondary notification of TGIC may be required,
where an applicant or other introducer (importer) of TGIC, becomes aware of any
circumstances which may warrant a reassessment of its hazards and risks. Specific
circumstances include:
a) The function or use of TGIC has changed, or is likely to change, significantly;
b) The amount of TGIC introduced into Australia has increased, or is likely to
increase significantly;
c) Manufacture of TGIC has begun in Australia; or
d) Additional information has become available to the applicant/notifier as to the
adverse health and/or environmental effects of TGIC.
The Director must be notified within 28 days of the introducer becoming aware of
any of the above circumstances.
Secondary Notification Assessment
26
Appendix 1
Sample Material Safety Data Sheet
for Triglycidylisocyanurate
Triglycidylisocyanurate 27
Secondary Notification Assessment
28
Triglycidylisocyanurate 29
Secondary Notification Assessment
30
Triglycidylisocyanurate 31
Appendix 2
RECOMMENDATIONS FOR ATMOSPHERIC MONITORING
AND
CONTROL OF OCCUPATIONAL EXPOSURE (adapted from the TGIC-1 report)
A2.1 Atmospheric monitoring
Atmospheric monitoring in both powder coating manufacturing plants and spray-painting
establishments should be carried out routinely. The frequency of monitoring should ensure
that the occupational exposure limit of 0.08 mg/m3 for TGIC is not being exceeded and that
the health of workers is therefore being protected. Atmospheric monitoring provides a
quantitative estimate of worker exposure, identifies areas where high levels of atmospheric
TGIC occur and provides a basis for measuring the effectiveness of control improvements.
As manufacturers of powder coatings handle 'pure' (technical grade) TGIC, routine air
monitoring of total dust and TGIC should be carried out. Air monitoring in these plants
should be carried out where exposure is likely to occur, such as where the filling of
hoppers, milling, extrusion and bagging takes place.
Routine air monitoring of spray-painting workshops should be carried out to ensure that the
exposure limit of 0.08 mg/m3 for TGIC is not being exceeded. The most accurate method
is to measure atmospheric levels of TGIC, but it is recognised that this method may not be
practical. Routine monitoring for total dust may be more practical. However, when
measuring total dust it must be assumed that all TGIC in the powder coatings is
bioavailable. For example, in workplaces using five per cent TGIC powder coating, the
total dust level should not exceed 1.6 mg/m3. Monitoring should be carried out where
worker exposure to TGIC in spray painting workshops is likely to occur, such as during
filling hoppers, spraying and clean-up operations.
Methods used for air monitoring and determination of TGIC content have been received
from Nissan Chemical Industries Ltd, Japan, and Ciba-Geigy Pty Ltd, Switzerland, and are
provided as Attachment 1 and Attachment 2*. The validity and suitability of these
monitoring techniques have not been assessed in this report.
For advice and assistance in monitoring contact, state and territory occupational health and
safety authorities.
A2.2 Control of occupational exposure
Consistent with good occupational hygiene principles, all worker exposure should be
minimised and spray painters and manufacturers of powder coatings should aim for the
lowest practicable levels of atmospheric TGIC and TGIC powder coating. In any case, the
levels should not exceed the exposure limit of 0.08 mg/m3 for TGIC.
* Attachments 1 and 2 are not reproduced in this appendix ?refer to TGIC-1 report.
Secondary Notification Assessment
32
Experience has shown that this level can be achieved and maintained in powder coating
manufacturing plants where there are hazard control measures, safe work practices and,
where necessary, personal protective equipment is worn.
Data indicate that although the exposure limit can be achieved in spray paint workshops, it
was often exceeded where control measures, work practices and personal protective
equipment vary and often are inadequate.
The setting of an occupational exposure limit does not preclude efforts to further reduce
exposure. To minimise worker exposure to TGIC, the control measures listed below
should be followed. The control measures should be seen as a hierarchy, that is,
implemented in the sequence in which they are presented.
A2.2.1 Application of powder coating
Substitution
TGIC is used in powder coatings as a curing agent, primarily because it gives ultraviolet
stability to the paint film. TGIC-free powder coatings are available which meet the
specifications of the end users. Review of the hazards and efficacy of these TGIC-free
powder coatings was outside the scope of this assessment. Substitution with TGIC-free
powder coatings should be considered. However, substitution should only be with less
hazardous substances and the health hazards of any potential substitute should be known to
employers and employees.
Isolation
The spray painting process should be separate from other workplace activities, such as by
distance or in another building.
Engineering controls
The most effective engineering controls for reducing worker exposure are enclosure, local
exhaust ventilation and automation of the spray process. In particular, this assessment
recommends that:
? spray painting of TGIC powder coatings should be performed in a booth;
? spray painting booths and equipment should be in accordance with Australian
Standard AS3754 -1990 - Safe Application of Powder Coatings by
Electrostatic Spraying. In particular, the design of the booth should be such
that airborne powder does not escape from the booth into the workplace. For
all installations, local exhaust ventilation should be provided and the average
air velocity through each booth opening should be not less than 0.4 m/sec;
? local exhaust ventilation should be used when spraying, during filling of
hoppers, when reclaiming powder and during clean-up;
? automatic spray guns, feed lines and feed equipment should be used;
? spray gun air pressure should be minimised to prevent over spray as this could
result in unnecessary powder build-up within the spray booth;
? the power supply and powder coating feedlines should be interlocked with the
air extraction system so that if a fault develops in the ventilation system, the
powder coating and power supplies are cut off;
Triglycidylisocyanurate 33
? the spread of dust within the powder coating building should be minimised.
Circumstances leading to draughts and air turbulence should be evaluated and
controls implemented;
? operations of opening powder coating packages, loading of hoppers and
reclaiming powder should be contained to prevent or minimise the generation
of dusts;
? the layout of the workstation and the size of the hopper opening should be such
that generation of dust is minimised in filling the hopper; and
? other methods in the use of hoppers should be considered, namely:
large hoppers should be used to avoid frequent refilling of smaller units,
and
preference should be given to the use of powder coatings supplied in drums
which allow mechanical transfer of the powder to hoppers.
Safe work practices
Safe work practices are necessary to supplement the engineering control measures in order
to minimise worker exposure.
Safe work practices should include:
? work practices designed to avoid the generation of dust;
? restricting access to spray painting areas;
? designing a safe workplace so that the spray painter is never between the object
to be sprayed and the airflow of contaminated air;
? situating the articles to be sprayed sufficiently within the booth to avoid
ricochet;
? implementing good personal hygiene practices, for example, powder coating
dust should not be allowed to collect on the face, exposed body areas should be
thoroughly washed and overalls should be regularly cleaned;
? storing powder coating and waste powder in a designated area and access
restricted;
? cleaning booths and surrounding areas on a regular basis;
? promptly cleaning-up spills of powder coatings to reduce the spread of TGIC;
? not using compressed-air or dry sweeping during clean-up operations;
? using a spark-proof squeegee when a wet clean-up is required;
? emptying vacuum cleaners in the booth and under exhaust ventilation;
? taking care to avoid the generation of dust during disposal of waste powder.
? waste powder being baked in the original box for disposal to landfill as a solid;
? vacuuming primary decontamination of work clothing;
? checking regularly the cleaning and maintenance of plant equipment, including
ventilation and spray equipment and filters; and
? proper induction training and general training of workers about the potential
hazards of spraying with TGIC powder coatings and in the safe work practices
necessary to minimise exposure.
Secondary Notification Assessment
34
Electrostatic spray painting brings with it electrical hazards and additional requirements for
safe work practices are required. For example, all equipment, including spray guns and
booth, should be earthed. All hooks used to suspend objects to be sprayed should be
cleaned prior to re-use in order to maintain effective metal contact. Earthing of equipment,
objects being coated and personnel ensures maximum coating efficiency, reduces free dust
and prevents build-up of static charges capable of causing ignition.
Personal protective equipment
Control of worker exposure should be achieved as far as is practicable by means other than
the use of personal protective equipment. However, when other control measures, such as
engineering controls and safe work practices, do not adequately protect the worker, then
personal protective equipment should be worn.
Personal protective equipment should include full protective clothing including overalls,
gloves, head and eye protection and respiratory protection, selected and used in compliance
with relevant Australian Standards. In particular:
? a full-face air-supplied particulate respirator should be worn, which complies
with AS 1716 - 1991 - Respiratory Protective Devices, and used in accordance
with AS 1715 1991 -Selection, Use and Maintenance of Respiratory Protective
Devices;
? the respiratory protective equipment should provide head covering to avoid
dust build-up around the edges of the face masks. A ventilated full-head
covering may also be more comfortable in a hot environment;
? during manual spraying, the gun-hand must not be insulated from the gun.
Either the gun hand should be cowled by a cover sleeve or the palm of an
insulating glove may be cut out. Operators standing outside a booth and
spraying inside a booth through an aperture should wear this type of protective
equipment; and
? anti-static and conductive footwear should be provided.
Workers who may come into direct contact with TGIC powder coatings include persons:
? filling hoppers;
? manually spraying powder coatings, including 'touch-up' spraying;
? reclaiming powder;
? emptying or cleaning industrial vacuum cleaners;
? cleaning spray booths, filters and other equipment; and
? cleaning up major spills of powder coating.
A2.2.2 Manufacture of powder coating
Where applicable, the controls measures outlined above for spray painting should be
implemented in the powder coating manufacturing plant. These measures include isolation
of the formulation process, enclosure, automation, local exhaust ventilation and the wearing
of personal protective equipment when necessary. Any open process or leakage will
increase worker exposure. Any manual process will also increase worker exposure.
Local exhaust ventilation should be provided when filling the hoppers, when adding to the
mixer, during mixing, extrusion and bagging, and at open transfer points.
Triglycidylisocyanurate 35
Personal protective equipment should be used when other control measures do not provide
adequate protection. In the powder coating manufacturing plants, personal protective
equipment worn by workers should be the same as that recommended for spray application,
which is described above.
The most likely activities where workers may be exposed are:
? filling hoppers;
? mixing, extrusion, pulverizing, sieving and bagging processes;
? reclaiming TGIC and powder coatings;
? emptying or cleaning industrial vacuum cleaners;
? cleaning up major spills of TGIC and powder coating;
? working in the quality control laboratory, such as during test spraying; and
? cleaning spray booths in quality control laboratory.
Secondary Notification Assessment
36
References
Ciba-Geigy Ltd (1986) Chromosome studies on male germinal epithelium of
mouse spermatogonia (No. 850067). Basel, Switzerland, Ciba-Geigy Ltd,.
C.I.T. (Centre International de Toxicologie) (1995) 13-Week toxicity study and
fertility study by oral route (dietary admixture) in male rats No. 11099 TCR,
Evreux, France.
C.I.T. (Centre International de Toxicologie) (1999) Carcinogenicity study in male
rats No. 11117 TCR, Evreux, France.
Ciba-Geigy Ltd (1988) Report on the test for ready biodegradability of TK 10622
in the modified sturm test ( No. 884053). Basel, Switzerland, Ciba-Geigy Ltd.
Ciba-Geigy Ltd (1988a) Skin sensitization test in the guinea pig, modified
maximisation test ( No. 884210). Basel, Switzerland, Ciba-Geigy Ltd.
Clottens FL, Mandervelt C, Demedts M, & Nemery B (1996). Limitations of the
local lymph node assay used for the prediction of respiratory sensitisers [abstract].
Proceedings of the Annual Congress of the European Respiratory Society
(Stockholm, September 7-11, 1996), ERS Journals Ltd.
Grutzner I (1997) Ready biodegradability of PT801 (TK10622) in a CO2 evolution
(Modified Sturm Test). Sponsored by Ciba Specialty Chemicals Inc., Switzerland.
Study Project No: 663928.
Hazleton Laboratories America Inc (1989) Mutagenicity test on PL88-810 in the
mouse spermatogonial cell cytogenetic assay (No. 10386-0-474). USA, Hazleton
Laboratories America Inc.
Hazleton Microtest (1991) Study to evaluate the chromosome damaging potential
of TK 10622 (PT 810 [TGIC, 97%]) by its effects on the spermatogonial cells of
treated mice. Heslington, York, United Kingdom, Hazleton Microtest.
Mandervelt C, Clottens FL, Demedts M, & Nemery B (1997) Assessment of the
sensitization potential of five metal salts in the murine lymph node assay.
Toxicology, 120(1):65-73.
McDonald JC (2000), personal communication, data from the SWORDS
surveillance scheme in the UK.
Meuleman L & Goossens A (1999) Sensitization to triglycidylisocyanurate (TGIC)
with cutaneous and respiratory manifestations. Allergy, 54(7):752-6.
National Institute of Environmental Health Sciences (NIEHS) (1999) The murine
local lymph node assay: a test method for assessing the allergic contact dermatitis
potential of chemicals/compounds, NIH Publication No. 99-4494.
NICNAS (1994) Priority Existing Chemical No. 1: Triglycidylisocyanurate
(TGIC): full public report. Canberra, Australian Government Publishing Service.
Triglycidylisocyanurate 37
NOHSC (1994a) National code of practice for the labelling of workplace
substances [NOHSC:2012(1994)]. Canberra, ACT, Australian Government
Publishing Service.
NOHSC (1994b) National model regulations for the control of workplace
hazardous substances [NOHSC:1005(1994)]. Canberra, ACT, Australian
Government Publishing Service.
NOHSC (1994c) National code of practice for the preparation of material safety
data sheets [NOHSC:2011(1994)]. Canberra, ACT, Australian Government
Publishing Service.
NOHSC (1995) Guidelines for health surveillance [NOHSC:7039(1994/95)].
Canberra, ACT, Australian Government Publishing Service.
NOHSC (1999) Approved criteria for classifying hazardous substances
[NOHSC:1008(1999)]. Canberra, ACT, Australian Government Publishing
Service.
OECD (1981) Guidelines for testing of chemicals. Paris, France, Organisation for
Economic Cooperation and Development.
Piirila P, Estlander T, Keskinen H, Jolanki R, Laakkonen A, Pfaffli P, Tupasela O,
Tuppurainen M, & Nordman H (1997) Occupational asthma caused by triglycidyl
isocyanurate (TGIC). Clin Exp Allergy, 27(5):510-4.
RCC (Research & Consulting Company Ltd.) (1997) Contact hypersensitivity to
TK 10622 in albino guinea pigs. Maximization Test No. 661634, Itingen,
Switzerland.
Safepharm Laboratories Ltd (1988) TEPIC-G: Magnusson and Kligman
maximisation study in the guinea pig (No. 14/14). Derby, United Kingdom,
Safepharm Laboratories Ltd.
Safepharm Laboratories Ltd (1991) TEPIC SP: Five-day repeat exposure inhalation
toxicity study in the male mouse (No. 14/68). Derby, United Kingdom, Safepharm
Laboratories Ltd.
Safepharm Laboratories Ltd (1992) TGIC technical and TGIC ten per cent
powder: chromosome analysis in mouse spermatogonial cells, comparative
inhalation study (No. 14/75) (Draft), Derby, United Kingdom, Safepharm
Laboratories Ltd.
Shell Research Ltd (1971) Toxicity studies on the diglycidyl esters of
tetrahydrophthalic and hexahydrophthalic acids and of triglycidylisocyanurate:
repeated dosing experiments with rats (TLGR.0019.71). London, United Kingdom,
Shell Research Ltd.
Secondary Notification Assessment
38
ORDER FORM FOR NICNAS PRODUCTS
I wish to purchase: Quantity
NICNAS "Handbook for Notifiers"@ AUD $103.00 each ...........
Australian Inventory of Chemical Substances (AICS) CD ROM @ $195.00
annual subscription (free six monthly update) within Australia only ...........
Copy/s of Full Public Report/s for the following new chemical assessment/s:
Include NICNAS reference number (no charge): ...........
Copy/s of Full Public Report/s for the following priority existing chemical (PEC)
assessment/s (no charge):
Triglycidylisocyanurate (TGIC) ...........
Triglycidylisocyanurate (TGIC) (Secondary Notification) ...........
`Savinase' ?Proteolytic Enzymes in Detergents ...........
Glutaraldehyde ...........
HCFC-123 ...........
HCFC-123 (Secondary Notification) ...........
Sodium ethyl xanthate ...........
Sodium ethyl xanthate (Secondary Notification) ...........
2-butoxyethanol ...........
1,4-Dioxane ...........
Trichloroethylene ...........
Chrysotile asbestos ...........
Acrylonitrile ...........
N-vinyl-2-pyrrolidone ...........
Glycolic acid ...........
para-dichlorobenzene ...........
ortho-dichlorobenzene ...........
All prices include postage and packaging within Australia and by SEAMAIL overseas. For
AIRMAIL please include an additional $50.00 for each Handbook and $10.00 for each other
NICNAS product.
Overseas only: Please send by AIRMAIL. YES / NO
ALL ORDERS MUST BE ACCOMPANIED BY PREPAYMENT IN AUSTRALIAN
DOLLARS. PURCHASE ORDERS NOT ACCEPTED
I enclose $....................cheque/money order payable to National Occupational Health &
Safety Commission drawn on an Australian bank in Australian dollars
OR Bankcard [ ] Visacard [ ] Mastercard [ ]
Card Number:______________________Expiry Date:___________________________
Card Holder:_______________________Signature:_____________________________
Name of Recipient:_______________________________________________________
Position: _______________________________________________________________
Company:______________________________________________________________
Address:_______________________________________________________________
____________________________________________Postcode___________________
Telephone: (___)__________________Fax:(___)_______________________________
Send this order to : National Occupational Health & Safety Commission
Finance Section, GPO Box 58, Sydney NSW 2001, Australia
Triglycidylisocyanurate 39
|