The Pivotal Role of Electron Microscopic Evaluation in Investigation of the Cardiotoxicity of bis(2-chloroethoxy)methane in Rats and Mice

Electron microscopy and light microscopy have been used to evaluate the cardiotoxicity of bis(2-chloroethoxy)methane (CEM) in F344/N rats and B6C3F1 mice. Rats received vehicle control or CEM at 50 mg/kg/day, and mice, vehicle control or CEM at doses up to 100 mg/kg/day, by oral gavage for up to sixteen days. Cardiotoxicity in rats at 50 mg/kg consisted of myocardial degeneration, including myocardial inflammation, myofiber vacuolation, and/or myofiber necrosis. There was no light microscopic evidence for cardiotoxicity in mice even at doses twice that of rats, but cardiotoxic damage was seen after electron microscopic evaluations including mitochondrial disintegration and vacuolation. Mice with mitochondrial damage may be more susceptible to subsequent cardiotoxic events and have a reduced capacity to respond when energy demands increase. Oral treatment of rats with CEM caused cardiotoxic lesions similar to those reported after dermal administration (Dunnick, Johnson, et al. 2004). The F344/N rat is more sensitive than the B6C3F1 mouse to the cardiotoxic effects of CEM.