© 1989 Oxford University Press
research-article |
Lack of Selective Developmental Toxicity of Three Butanol Isomers Administered by Inhalation to Rats
Division of Biomedical and Behavioral Science, National Institute for Occupational Safety and Health 4676 Columbia Parkway, Cincinnati, Ohio 45226, and Intox Laboratories Inc. 1 Intox Drive, Redfield, Arkansas
Received March 31, 1988; accepted September 22, 1988
Lack of Selective Developmental Toxicity of Three Butanol Isomers Administered by Inhalation to Rats. NELSON, B. K., BRIGHTWELL., W. S., KHAN, A., BURG, J. R., AND GOAD, P. T. (1989). Fundam. Appl Toxicol. 12,469–479. As part of an ongoing study of the developmental toxicology of industrial alcohols, this report presents the results of the teratology assessments of 1-butanol, 2-butanol, and t-butanol administered by inhalation to rats. Groups of approximately 15 Sprague-Dawley rats were exposed at 8000, 6000, 3500, or 0 ppm 1-butanol, 7000, 5000, 3500, or 0 ppm 2-butanol, or 5000, 3500, 2000, or 0 ppm t-butanol for 7 hr/thy on Gestation Days 1–19 (sperm=0). In each ease, the highest concentration was selected to produce maternal toxicity. Dams were sacrificed on Gestation Day 20, and fetuses were individually weighed, tagged and examined for external malformations. One-half of the fetuses were stained and examined for skeletal abnormalities, and the other half were examined for visceral defects using the Wilson technique. For each butanol isomer examined, the highest concentration (and the intermediate in some eases) was maternally toxic, as manifest by reduced weight gain and feed intake. Even at a maternally toxic dose, and in spite of a dose-dependent reduction in fetal weights for each isomer, the only teratogenicity observed was a slight increase in skeletal malformations (primarily rudimentary cervical ribs), seen with the highest concentration of 1-butanol. Thus, although teratogenicity was observed at 8000 ppm 1-butanol, and developmental toxicity was observed with each of the butyl alcohol isomers studied, concentrations 50 times the current permissible exposure limits for these three butanol isomers do not produce teratogenicity in rats.