Prenatal developmental toxicity of gavage or feeding doses of 2-sec-butyl-4,6-dinitrophenol in rats.
This study evaluated the prenatal developmental toxicity of the pesticide 2-sec-butyl-4,6-dinitrophenol (dinoseb). Pregnant rats were given dinoseb by gavage at 0, 8.0 or 10 mg/kg bw/day on days 6-15 of gestation, or in the diet at 0, 120 or 200 ppm (0, 6.52 or 8.50 mg/kg bw/day) on days 6-16 of gestation, and litters were evaluated on day 20 of gestation. Maternal toxicity was observed as evidenced by significantly decreased body weight gain and reduced food consumption during the administration period in all the dinoseb-treated groups, and two dams died at 10 mg/kg bw/day. Significantly lower fetal weights and delayed skeletal ossification was observed in the dinoseb-treated groups except for the group fed dinoseb at 120 ppm. The teratogenic potential of the gavage dose of dinoseb was confirmed as evidenced by increased incidences of fetuses with external and skeletal malformations at 10 mg/kg bw/day. The incidence of fetuses with microphthalmia was significantly increased at this dose. On the other hand, feeding doses of dinoseb up to 200 ppm did not induce teratogenicity in this study. These data indicate that dinoseb is teratogenic at maternally toxic doses, but the exposure range of dinoseb at which malformations occur seems to be narrow.
Division of Risk Assessment, Biological Safety Center, National Institute of Health Sciences, Tokyo, Japan. mariko@nihs.go.jp
Mariko
M
Matsumoto
Sakiko
S
Fujii
Akihiko
A
Hirose
Makoto
M
Ema
D019297:2,4-Dinitrophenol / Q000031:analogs & derivatives; D000818:Animals; D004750:Enteral Nutrition / Q000009:adverse effects; D005260:Female; D020567:Fetal Weight / Q000187:drug effects; D005333:Fetus / Q000187:drug effects; D008297:Male; D009139:Musculoskeletal Abnormalities / Q000150:complications; D018529:Nutritional Support / Q000009:adverse effects; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013047:Specific Pathogen-Free Organisms; D013723:Teratogens / Q000494:pharmacology / Q000633:toxicity*; D015431:Weight Loss
D013723:Teratogens; D019297:2,4-Dinitrophenol; C018527:dinoseb