Phase-Specific Developmental Toxicity in Mice Following Maternal Methanol Inhalation

Phase-Specific Development Toxicity in Mice Following MaternalMethanol Inhalation. BOLON, B., DORMAN, D. C., JANSZEN, D.,MORGAN, K. T., AND WELSCH, F.(1993). Fundam. Appl. Toxicol.21, 508–516. Methanol is toxic to embryos of mice and rats when inhaled bydams at high concentrations. The present studies examined methanol-induceddevelopmental toxicity following inhalation exposure (6 hr/day)of pregnant CD-1 mice to 5000, 10,000, or 15,000 ppm eitherthroughout organogenesis (GD 6–15), during the periodof neural tube development and closure (GD 7–9), or duringa time of potential neural tube reopening (GD 9–11). Transientneurologic signs and reduced body weights were observed in upto 20% of dams exposed to 15,000 ppm. Examination of near-termfetuses revealed embryotoxicity (increased resorptions, reducedfetal weights, and/or fetal malformations) at 10,000 and 15,000ppm, while 3-day exposures at 5000 ppm yielded no observableadverse effects. Terata included neural and ocular defects,cleft palate, hydronephrosis, deformed tails, and limb (pawand digit) anomalies. Neural tube defects and ocular lesionsoccurred after methanol inhalation between GD 7–9, whilelimb anomalies were induced only during GD 9–11; cleftpalate and hydronephrosis were observed after exposure duringeither period. These findings were consistent with prior reportsthat maternal methanol inhalation at high levels induces developmentaltoxicity in a concentration dependent manner. Furthermore, ourdata indicate that the spectrum of teratogenic effects dependedupon both the timing (i.e., stage of embryonic development)and the number of methanol exposures.