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Isopropyl benzene (cumene) [MAK Value Documentations, 2013]


Jahnke, G; Hamann, I; Laube, B; Greim, H; Hartwig, A; MAK Commission; et al; Arand, Michael (2016). Isopropyl benzene (cumene) [MAK Value Documentations, 2013]. The MAK Collection for Occupational Health and Safety, 1(1):53-90.

Abstract

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.

Abstract

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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Item Type:Journal Article, not_refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Pharmacology and Toxicology
07 Faculty of Science > Institute of Pharmacology and Toxicology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:28 January 2016
Deposited On:17 Oct 2019 11:16
Last Modified:17 Oct 2019 11:16
Publisher:Wiley-VCH Verlag
ISSN:2509-2383
ISBN:9783527600410
OA Status:Closed
Publisher DOI:https://doi.org/10.1002/3527600418.mb9882e5416

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