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

Methanol (MeOH), a widely used industrial solvent, has been proposed a s an alternative motor vehicle fuel. Inhaled MeOH is developmentally t oxic in both rats and mice but the mouse is more sensitive than is the rat. The contribution of the embryo to this differential sensitivity was studied in whole embryo culture (WEC) using equivalent stage rat ( day 9) and mouse (day 8) embryos (plug day = day 0). Rat embryos were explanted and cultured in 0, 2, 4, 8, 12 or 16 mg MeOH/ml rat serum fo r 24 h and then transferred to rat serum alone for 24 h. Embryonic dev elopment of the 2 and 4 mg MeOH/ml groups was not significantly differ ent from the controls whereas the higher concentrations resulted in a concentration related decrease in somite number, head length and devel opmental score. The 12 mg/ml dose resulted in some embryolethality as well as dysmorphogenesis, while the highest dose was embryolethal. MeO H was dysmorphogenic in vitro in rat embryos at a MeOH concentration c omparable to that reported in maternal serum following teratogenic in vivo exposures. Day 8 mouse embryos were explanted and cultured in 0, 2, 4, 6 or 8 mg MeOH/ml culture medium (75% rat serum, 25% Tyrode's sa lt solution) for 24 h. Embryonic development in the 2 mg/ml MeOH group was not significantly different from the controls but all higher conc entration groups bad a significant decrease in developmental score and crown-rump length. The high concentration group also suffered 80% emb ryolethality. Thus, mouse embryos were affected at MeOH concentrations which were not dysmorphogenic or embryotoxic in the rat, suggesting t hat the higher sensitivity of the mouse to the developmental toxicity of inhaled methanol is due, at least in part, to greater intrinsic emb ryonal sensitivity of this species to methanol.