J. Arts, M. Kellert, L. Pottenger
Apr 1, 2019
Citations
1
Influential Citations
6
Citations
Quality indicators
Journal
Regulatory Toxicology and Pharmacology
Abstract
Abstract Methyl Chloride (MeCl; Chloromethane) is a high production volume chemical (>1000 t/a) and is used as an industrial solvent. Based on cardiac lesions reported in developmental toxicity studies in mice, but not in rats, manufacturers decided to classify MeCl as a developmental toxicant, cat. 2. Recently, the European Chemical Agency required a developmental toxicity study in a non‐rodent species. No developmental toxicity was observed in rabbits in the recently completed, GLP, OECD 414 guideline study. In view of the absence of cardiac effects in rats and rabbits, the purpose of this review is to consider whether the cardiac effects reported in mice should be considered real effects and, if so, their potential for relevance to humans. This paper provides substantive new evidence with data from a third species and shows that an evaluation of the integrated scientific evidence indicates the reported developmental cardiac effects in mice, if not an artifact, are unlikely to be relevant to humans. As such the classification of MeCl for developmental toxicity was reconsidered. HighlightsCardiac lesions were reported in fetal mice following exposure to high concentrations of MeCl but were not replicated.These lesions, viz. reduced number of papillary muscles, were reported in fetal mice but not in fetal rats or rabbits.The normal anatomy and variability in appearance of tiny papillary muscles in the fetal mouse heart complicate evaluation.Number, length, and shape of cardiac papillary muscles are reported to be variable in humans.Integrated evidence indicates these cardiac effects in fetal mice, if not an artifact, are unlikely to be relevant to humans.