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EC number: 218-485-4
CAS number: 2162-73-4
Male rats of both the Fisher 344 and
Sprague-Dawley strain exposed to 0.1 or 0.3 ppm TDI showed a slight but
significant reduction in body weight gain. A greater incidence of
sneezing occurred in the Sprague-Dawley males suggesting slight
respiratory irritation. No adverse effects were observed in the mouse
and hamster study.
Rats did not exhibit changes in the lower
respiratory tract (histopathology of upper respiratory tract in
progress) nor was there any trend of increased mortality in any group.
Rats exposed at 0.15 ppm had significantly less increase in weight, only
in the first 12 weeks of the study. No specific target tissue has been
identified. The tumour pattern in the rat study was similar in the
control and in the treated groups and corresponded to historical data.
The study demonstrated no evidence of any neoplastic response. These
results are supported by tests on mutagenicity. There was no evidence of
a mutagenic response in vivo as demonstrated by the results of a
micronucleus test on rats and mice exposed for four weeks to TDI at
exposure concentrations up to and including 0.15 ppm. As far as the
incomplete rat study can be interpreted, levels which cause no primary
irritative effect also do not result in any other effect of
toxicological significance. As a result of these studies the current
occupational exposure levels are not considered to represent a serious
health hazard. The possible sensitization to TDI, however, needs special
The carcinogenicity of the test material was
investigated in rats by Loeser et al (1983). The test was conducted
similar to OECD TG451. Groups of male and female rats (21 animals per
sex per group) were exposed to 0,05 and 0.15 ppm of toluene-diisocyanate
(TDI) by inhalation for 6 h/day, 5 days/week for approx. 2 years. Type
and incidence of tumours and the number of tumour-bearing animals were
recorded. Additionally clinical signs, mortality, body weight gain,
haematology, biochemistry, urinalysis, and cytogenicity were recorded.
At termination of the study necropsy and histopathological examination
were performed and organ weights recorded. No exposure-related signs
occurred during the study. At termination of the study (at week 110 for
males and at week 108 for females) total percentage deaths were 65% in
controls, 67% low dose, 71% high dose males and 68% in controls, 75% low
dose, 64% high dose females. Male and female rats of the 0.15 ppm group
gained less weight during the first 12 weeks of the study. Type and
incidence of tumours and the number of tumour-bearing animals did not
indicate any carcinogenic effect. Haematology, biochemistry, urinalysis,
and cytogenicity did not reveal any untoward effect. Histopathological
examination in the rat study has not been completed, but no effect in
the respiratory tract or in any other tissue has yet been seen.
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