title: Effect of oral dosing vehicles on the developmental toxicity of flubendazole in rats.
abstract: Flubendazole was suspended in deionized water or olive oil and administered by gavage once daily to pregnant rats on Days 8-15 of pregnancy to examine if the embryolethal and teratogenic doses were affected by the vehicles used. Flubendazole in olive oil caused a statistically significant increase in embryolethality at doses of 7.83 mg/kg per day and higher, with complete resorption in all dams at 31.33 mg/kg per day. When flubendazole was suspended in deionized water, a significant increase in embryolethality occurred only at a maternal dose of 125.32 mg/kg per day. The proportion of litters with anomalous fetuses was significantly increased at doses of 31.33 mg/kg per day and above when flubendazole was administered in deionized water, but increased at doses at four times lower when flubendazole was administered as in olive oil. Administered as a single dose in olive oil on any one of Days 6-12 of pregnancy, a flubendazole dose of 31.33 mg/kg caused significant increases in embryolethality and decreased fetal body weights on Days 7-9, with an 82.7% incidence of embryolethality on Day 8, with complete resorption in 5 of the 8 dams. The critical periods for teratogenic effects were between Days 8 and 11 of pregnancy, with Day 9 being the most critical. Fetuses with gross, skeletal, or internal anomalies were seen in dams given a single dose of as low as 7.83 mg/kg.
authors.affiliation: National Veterinary Assay Laboratory, Ministry of Agriculture, Forestry and Fisheries, 1-15-1 Tokura, Kokubunji, 185-8511 Tokyo, Japan. yosimuh@nval.go.jp
authors.forename: Haruo
authors.initials: H
authors.lastname: Yoshimura
mesh_terms: D000014:Abnormalities, Drug-Induced / Q000473:pathology; D000015:Abnormalities, Multiple / Q000139:chemically induced*; D000284:Administration, Oral; D000818:Animals; D000871:Anthelmintics / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D005327:Fetal Resorption / Q000139:chemically induced; D020567:Fetal Weight / Q000187:drug effects; D005865:Gestational Age; D008098:Litter Size / Q000187:drug effects; D008431:Maternal-Fetal Exchange; D008463:Mebendazole / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity*; D000069463:Olive Oil; D014677:Pharmaceutical Vehicles / Q000008:administration & dosage*; D010938:Plant Oils / Q000008:administration & dosage; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013723:Teratogens / Q000633:toxicity*; D014867:Water / Q000008:administration & dosage / Q000737:chemistry
chemical_list: D000871:Anthelmintics; D000069463:Olive Oil; D014677:Pharmaceutical Vehicles; D010938:Plant Oils; D013723:Teratogens; D014867:Water; D008463:Mebendazole; C018945:flubendazole