Developmental toxicity of orally administered thiabendazole in Sprague-Dawley rats and New Zealand white rabbits.
The developmental toxicity of thiabendazole (TBZ) was assessed in studies in New Zealand white rabbits and Sprague-Dawley rats. The doses of TBZ for these studies were based on decreases in maternal weight gain in dose range-finding studies in pregnant females of each species. In rabbits, TBZ was administered orally at doses ranging from 24 to 600 mg/kg body weight/day in two separate studies. In rats, TBZ was administered at doses of 10, 40 or 80 mg/kg body weight/day. In all studies, TBZ was administered daily by gavage in aqueous suspension on gestation days 6 to 17. In the initial rabbit study, weight loss occurred in the 600 mg/kg/day group and weight gain decreased in the 120 mg/kg/day group. In addition, there were four complete litter resorptions and four abortions in the 120 and 600 mg/kg/day groups, respectively. To determine whether these changes (known to occur spontaneously in rabbits) were reproducible, the study was repeated. In this study, decreased maternal weight gain and decreased foetal weights were found at 600 mg TBZ/kg/day, but there was no evidence of selective developmental toxicity. Similarly, in rats TBZ produced decreased maternal weight gain (12 to 26%) associated with slight (5 to 7%) decreases in foetal weights at doses of 30 and 80 mg/kg/day. No changes were found at 10 mg TBZ/kg/day and no evidence of selective developmental toxicity or teratogenicity was found at any dose. On the basis of these results, it is concluded that TBZ is not teratogenic or selectivity foetotoxic in rats or rabbits.
Lankas
G R
GR
Department of Safety Assessment, Merck Research Laboratories, West Point, PA 19486.
Wise
D L
DL
D000014:Abnormalities, Drug-Induced; D000284:Administration, Oral; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D005260:Female; D005313:Fetal Death / Q000139:chemically induced; D005327:Fetal Resorption / Q000139:chemically induced; D011247:Pregnancy; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D013723:Teratogens / Q000633:toxicity*; D013827:Thiabendazole / Q000008:administration & dosage / Q000633:toxicity*
D013723:Teratogens; D013827:Thiabendazole