Teratological Assessment of Methanol and Ethanol at High Inhalation Levels in Rats

Teratological Assessment of Methanol and Ethanol at High InhalationLevels in Rats. NELSON, B. K., BRIGHTWELL, W. S., MACKENZIE,D. R., KHAN, A., BURG, J. R., WEIGEL, W. W., AND GOAD, P. T.(1985). Fundam. Appl. Toxicol. 5, 727–736. Alcohols arewidely used as industrial solvents. In spite of the fact thatethanol is a human teratogen, there has not been systematicinvestigation of the potential teratogenic effects of otheralcohols, particularly using the inhalation route of exposure,as would be appropriate in assessing occupational and environmentaltypes of experience. As part of a large teratological examinationof industrial alcohols, methanol and ethanol were administeredby inhalation to groups of approximately 15 pregnant Sprague-Dawleyrats. Methanol was administered at 20,000 ppm (20ME), 10,000ppm (10ME), 5000 ppm (5ME), and 0 ppm (MECO) for 7 hr/day onDays 1–19 of gestation (Days 7–15 for 20ME). Ethanolwas administered at 20,000 ppm (20ET), 16,000 ppm (16ET), 10,000ppm (10ET), and 0 ppm (ETCO) for 7 hr/day on Days 1–19of gestation. Dams were sacrificed on Day 20 (sperm=Day 0).One-half of the fetuses were examined using the Wilson techniquefor visceral defects, and the other half were examined for skeletaldefects. The highest concentration of methanol (20ME) producedslight maternal toxicity and a high incidence of congenitalmalformations (p < 0.001), predominantly extra or rudimentarycervical ribs and urinary or cardiovascular defects. Similarmalformations were seen in the 10ME group, but the incidencewas not significantly different from controls. No adverse effectswere noted in the 5ME group. Dams in the 20ET group were narcotizedby the end of exposure, and maternal weight gain and feed intakewere decreased during the first week of exposure. The 16ET damshad slightly depressed weight gain (p < 0.01) during thefirst week of exposure, but there were no significant effectson feed consumption. There was no definite increase in malformationsat any level of ethanol, although the incidence in the 20ETgroup was of borderline significance