Role of formate in methanol‐induced exencephaly in CD‐1 mice

摘要: Mouse embryos develop exencephaly when dams are exposed by inhalation to high concentrations (⩾10,000 ppm) of methanol on gestational day 8 (GD8; copulation plug = GD0). The present study examined the role formate, an oxidative metabolite methanol, in development methanol-induced CD-1 mice and cultured mouse embryos. pharmacokinetics developmental toxicity sodium formate (750 mg/kg gavage), a 6-hr (10,000 or 15,000 ppm), gavage (1.5 g/kg) pregnant GD8 were determined. Gross morphological evaluations for neural tube closure status near-term fetuses performed. Decidual swellings maternal plasma analyzed formate. mean (± S.E.M.) end-of-exposure concentration was 223 ± 23 mM following 6-hr, ppm inhalation. There no changes blood decidual swelling under any exposure conditions. Peak levels (1.05 0.2 mM; control 0.5 0.3 mM) (2.0 1.1 from (GD8) given mg/kg, po) similar those observed (plasma 0.75 0.1 2.2 but did not result exencephaly. In cultures neurulating explanted GD 8, incidence cephalic dysraphism 9 + 6 hr significantly increased relative appropriate controls after 12-hr 375 (40 that exceeded vivo. These results suggest is direct effects parent compound administered at concentrations, rather than accumulation © 1995 Wiley-Liss, Inc.