The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated trimethylpentane (all isomers), considering all toxicity endpoints. Available unpublished study reports and publications are described in detail. The re‐examination determined that it is difficult to draw final conclusions from a carcinogenicity study of a mixture of 542 hydrocarbons and from mechanistical studies with some of their single components. Thus, the assignment to Carcinogen Category 3 A has been withdrawn. The critical effect is the acute effect on the central nervous system in rats. The NOAEC after 60 min inhalation is 500 ml 2,2,4‐trimethylpentane/m3. Experimental data from structurally analogous n‐alkanes and iso‐alkanes lead to the assumption that the concentration of 2,2,4‐trimethylpentane in the brain after 8 hours will be about twice as high as after one hour. The short half‐life in the brain, estimated to be about one hour, does not predict an accumulation during the work week. The same assumptions are made for the other trimethylpentane isomers. Thus, taking into consideration uncertainties in the extrapolation of animal to human data, a MAK value of 100 ml/m3 (470 mg/m3) is set for all trimethylpentane isomers. As the critical effect is systemic, trimethylpentane isomers are assigned to Peak Limitation Category II. The excursion factor of 2 is set as the estimated half‐life in the brain is one hour or even less. Prenatal developmental toxicity studies with trimethylpentane isomers are not available. For structurally analogous C8‐isoalkanes the NOAEC for developmental toxicity in rats is more than 1200 ml/m3. Acute neurotoxicity is critical, but the consequences of acute neurotoxic effects on in‐utero development of the nervous system are not known and studies on developmental neurotoxicity of C8‐alkanes are not available. Thus, trimethylpentane isomers are classified in Pregnancy Risk Group D. There are no clinical data and no data in animals concerning the sensitizing potential of trimethylpentane isomers. In analogy to n‐heptane, skin contact is not expected to contribute significantly to systemic toxicity. Completed: June 24, 2016
Hartwig et al. (Thu,) studied this question.