Evaluation of developmental toxicity of 1-butanol given to rats in drinking water throughout pregnancy.
The objective of this study was to evaluate the developmental toxicity of 1-butanol in rats. Pregnant rats were given drinking water containing 1-butanol at 0.2%, 1.0% or 5.0% (316, 1454 or 5654 mg/kg/day) on days 0-20 of pregnancy. A significant decrease in maternal body weight gain accompanied by reduced food and water consumption was found at 5.0%. No significant increase in the incidence of pre- and postimplantation embryonic loss was observed in any groups treated with 1-butanol. Fetal weight was significantly lowered at 5.0%. Although a significant increase in the incidence of fetuses with skeletal variations and decreased degree of ossification was found at 5.0%, no increase in the incidence of fetuses with external, skeletal and internal abnormalities was detected in any groups treated with 1-butanol. The data demonstrate that 1-butanol is developmental toxic only at maternal toxic doses. No evidence for teratogenicity of 1-butanol was noted in rats. Based on the significant decreases in maternal body weight gain and fetal weight, it is concluded that the no observed adverse effect levels (NOAELs) of 1-butanol for both dams and fetuses are 1.0% (1454 mg/kg/day) in rats.
Ema
M
M
Division of Risk Assessment, Biological Safety Research Center, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan. ema@nihs.go.jp
Hara
H
H
Matsumoto
M
M
Hirose
A
A
Kamata
E
E
D020001:1-Butanol / Q000633:toxicity*; D000014:Abnormalities, Drug-Induced / Q000453:epidemiology* / Q000209:etiology; D000284:Administration, Oral; D000818:Animals; D001846:Bone Development / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004326:Drinking; D004353:Drug Evaluation, Preclinical; D005260:Female; D047109:Fetal Development / Q000187:drug effects*; D020567:Fetal Weight / Q000187:drug effects; D008297:Male; D018811:Maternal Exposure; D019055:No-Observed-Adverse-Effect Level; D011247:Pregnancy; D051381:Rats; D013723:Teratogens / Q000633:toxicity*; D013997:Time Factors; D015430:Weight Gain / Q000187:drug effects
D013723:Teratogens; D020001:1-Butanol