Developmental toxicity of methylamines in mice

Abstract

Monomethylamine (MMA), dimethylamine (DMA), and trimethylamine (TMA) are endogenous substances as well as metabolites of methyl isocyanate, the chemical involved in the 1984 accident at Bhopal, India. Although methylamines exert several toxic effects including inhibition of protein turnover and oocyte RNA synthesis, their reproductive toxicity has not been investigated. We therefore studied the possible developmental toxicity of these amines using pregnant CD-1 mice and mouse embryo culture as experimental models. Intraperitoneal injections (daily from d 1 to 17 of gestation) of TMA at 2.5 and 5 mmol/kg/d significantly (p less than .001) decreased fetal body weight but not the placental weight or maternal body weight gain; however, 5 of 11 mice treated with 5 mmol/kg TMA died. Similar treatment with DMA and MMA did not exert any obvious maternal or fetal effects. All three methylamines, when added to embryos in culture, caused dose-dependent decreases in size, DNA, RNA, and protein content as well as embryo survival; the order of toxicity was TMA greater than DMA greater than MMA. The ability of methylamines to adversely affect fetal development suggests that these amines, especially trimethylamine, may act as endogenous teratogens under certain conditions.