Evaluation of developmental toxicity of Methyl Chloride (Chloromethane) in rats, mice, and rabbits.

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.