IN-VITRO ASSESSMENT OF THE EFFECT OF METHANOL AND THE METABOLITE, FORMIC-ACID, ON EMBRYONIC-DEVELOPMENT OF THE RAT

Inhalation studies in rats have indicated that methanol is embryotoxic at levels that are only mildly maternally toxic. In the present study , the embryotoxicity of methanol and its metabolite, formic acid, was evaluated using rat embryo culture. The results showed that both metha nol and formic acid have a concentration-dependent embryotoxic effect on the developing rat embryo in vitro. The no-effect concentration of methanol was 211.7 mu mol/ml culture medium, while embryotoxicity was observed at 286.5 mu mol/ mi. The no-effect concentration of formic ac id was 3.74 mu mol/ml, while a concentration of 18.66 mu mol/ml was as sociated with severe embryotoxicity. When embryos were grown in sera c ontaining 18.66 mu mol sodium formate/ml or in sera adjusted with hydr ochloric acid to pH values similar to those achieved with formic acid, the results indicated that both low pH and formate contributed to the observed embryotoxicity of formic acid. When the level of methanol fo und to be embryotoxic in the present study is compared to blood levels in the human following controlled industrial exposure there appears t o be a large margin of safety. However, plasma methanol levels are onl y one aspect of methanol toxicity in the human. Of greater significanc e is the formate level and the associated acidosis. However, it appear s that embryotoxicity due to low pH or high formate levels would only occur after very severe methanol intoxication. Based on these in vitro studies, current industrial safety limits would appear to provide pro tection for the developing embryo. (C) 1995 Wiley-Liss, Inc.