Evaluation of In Vivo Mutagenicity of Low-Dose Methylene Chloride in Mice

Abstract

Methylene chloride, a widely used industrial solvent, has been shown to be mutagenic by in vitro tests. The aim of this study was to determine in vivo mutagenicity. Groups of 20 Swiss-Webster (S/W) male mice were injected subcutaneously three times/week with 5 ml/kg of 5% vol/vol or 10% vol/vol solution of methylene chloride in corn oil for 4 weeks, followed by 1 week of no treatment. Other groups of 20 S/W male mice were exposed to airflow of 10 L/min carrying 100, 150, or 200 ppm of methylene chloride daily for 2 hr/day, 5 days/week for 6 weeks. Each study contained appropriate negative controls. Mating was started 1 week later for the injection group and 2 days later for the inhalation group. Each male mouse was mated with a S/W virgin adult female. The mating was allowed to continue for 2 weeks. Presence of a vaginal plug was taken as a sign of successful mating and was designated as day 0 of gestation. On day 17, the females were killed, and the fetuses were removed and processed. Male mice were killed, and the testes were removed, preserved in 10% formalin, and processed. No significant difference in any of the mutagenicity parameters was found between control and treated groups. No microscopic lesions were found in testes of the treated males.

The role of glutathione in the bacterial mutagenicity of vapour phase dichloromethane

“…Inhalation of DCM by mice results in the induction of clastogenic effects in the lungs, peripheral lymphocytes, and bone marrow , although it was not clastogenic in rodent bone marrow by intraperitoneal or subcutaneous injection Sheldon et al, 1987;Westbrook-Collins et al, 1990;Raje et al, 1988). and E. coli, it has been proposed that its mutagenicity in bacteria is mediated by glutathione (GSH) conjugation (Jongen et al, 1978(Jongen et al, , 1982Green, 1983).…”