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 conversion of MeOH to formate and the resulting acidosis. MeOH has been shown to be developmentally toxic in mice and rats both in vivo and in vitro, but rodents neither accumulate formate nor develop acidosis after MeOH exposure. To further assess the potential human developmental toxicity of MeOH exposure, we evaluated the developmental effects of sodium (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 embryos were cultured for 24 hours in the presence of Na-formate or formic acid. Rat and mouse embryos exposed to either agent for 24 hours exhibited a trend toward reduced growth and development and the number of abnormalities increased at the higher concentrations. Rat embryos exposed for 48 hours to either Na-formate or formic acid showed a trend toward reduced growth and development with increasing concentration. Embryo lethality and incidence of abnormal embryos were also increased at the higher concentrations. The anomalies observed in both species after exposure to either compound were primarily open anterior and posterior neuropore with less frequent incidence of rotational defects, tail anomalies, enlarged pericardium and delayed heart development. Exposure to Na-formate or formic acid for comparable periods of time results in comparable degrees of embryotoxicity at concentrations (mMolar) at least 4-fold lower than those previously reported for methanol exposure.
Andrews
J E
JE
Developmental Toxicology Division, Health Effects Research Laboratory, United States Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA.
Ebron-McCoy
M
M
Kavlock
R J
RJ
Rogers
J M
JM
D000014:Abnormalities, Drug-Induced; D000818:Animals; D046508:Culture Techniques; D004247:DNA / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian / Q000187:drug effects* / Q000473:pathology; D005314:Embryonic and Fetal Development / Q000187:drug effects*; D005260:Female; D005561:Formates / Q000633:toxicity*; D051379:Mice; D008813:Mice, Inbred ICR; D011247:Pregnancy; D011506:Proteins / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley
D005561:Formates; D011506:Proteins; C030544:formic acid; D004247:DNA