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1000
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Abstract/Summary
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The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated isopropyl benzene to derive a maximum concentration at the work place (MAK value), considering all toxicity endpoints. Available publications are described in detail. Isopropyl benzene caused adenomas in the nose of rats, and in mice adenomas and carcinomas in the lungs and adenomas in the liver. Genotoxic effects do not seem to be responsible for the carcinogenicity. Concerning the lung tumours of mice, it is assumed that ring hydroxylated metabolites stimulate cell proliferation, which can lead to tumour formation. In humans, the metabolism of aromatic molecules in the respiratory tissues is not yet clarified in detail and therefore carcinogenic effects of isopropyl benzene in humans cannot be excluded. Isopropyl benzene is therefore classified in Carcinogen Category 3B. Isopropyl benzene is not genotoxic, therefore, the derivation of a MAK value is possible. In agreement with the procedures used by the Commission, a MAK value of 10 ml/m3 was set, derived from a calculated BMDL of 35 ml/m3 for liver weight increase in the 14‐week study with rats and from the calculated BMDL of 42 ml/m3 for nasal adenomas in the 2‐year study in rats. On the basis of the mainly systemic effects, the classification in Peak Limitation Category II is retained. The half‐life in humans is considerably longer than 2 hours, so that the excursion factor of 4 is also retained. No foetotoxic or teratogenic effects were found in rats and rabbits up to 1200 and 2300 ml/m3, respectively. As the difference between the NOAEC for developmental toxicity and the MAK value is sufficiently large, damage to the embryo or foetus is unlikely when the MAK value is observed. The assignment to Pregnancy Group C is confirmed. Skin contact may contribute significantly to systemic toxicity and the designation with an “H” notation is retained. Sensitisation is not expected based on the result of a maximisation test.
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