DEVELOPMENTAL TOXICITY OF FORMATE AND FORMIC-ACID IN WHOLE-EMBRYO CULTURE - A COMPARATIVE-STUDY WITH MOUSE AND RAT EMBRYOS

Acute methanol (MeOH) toxicity in primates is attributed to the conver sion of MeOH to formate and the resulting acidosis. MeOH has been show n to be developmentally toxic in mice and rats both in vivo and in vit ro, but rodents neither accumulate formate nor develop acidosis after MeOH exposure. To further assess the potential human developmental tox icity of MeOH exposure, we evaluated the developmental effects of sodi um (Na) formate and formic acid in rodent whole embryo culture (WEC). Day 9 rat embryos were cultured for 24 or 48 hours and day 8 mouse emb ryos were cultured for 24 hours in the presence of Na-formate or formi c acid. Rat and mouse embryos exposed to either agent for 24 hours exh ibited a trend toward reduced growth and development and the number of abnormalities increased at the higher concentrations. Rat embryos exp osed for 48 hours to either Na-formate or formic acid showed a trend t oward reduced growth and development with increasing concentration. Em bryo lethality and incidence of abnormal embryos were also increased a t the higher concentrations. The anomalies observed in both species af ter exposure to either compound were primarily open anterior and poste rior neuropore with less frequent incidence of rotational defects, tai l anomalies, enlarged pericardium and delayed heart development. Expos ure to Na-formate or formic acid for comparable periods of time result s in comparable degrees of embryotoxicity at concentrations (mMolar) a t least 4-fold lower than those previously reported for methanol expos ure. (C) 1995 Wiley-Liss, Inc.()