Prenatal exposure to the fungicide dinocap causes behavioral torticollis, ballooning and cleft palate in mice, but not rats or hamsters

摘要

AbstractThe present study is an evaluation of the developmental toxicity of dinocap in three rodent species using an in vivo teratology screen. Our protocol uses postnatal viability, weight gain, and morphological and behavioral development through weaning to assess the developmental toxicity of compounds.Dinocap administered orally on days 7 to 16 of gestation to the CD‐1 mouse resulted in increased postnatal mortality at 25 mg/kg/d (80 in block 1 and 40 in block 2). Many of the treated pups that died during the neonatal period were “ballooned” and had cleft palates. Although there was no treatment related mortality in the 12 mg/kg/d dosage group, 6 (14/226) of these mice and 24 (23/96) of the survivors from the 25 mg/kg/d dosage group displayed torticollis (a twisting of the neck resulting in an abnormal tilting of the head). These tilted‐head mice held the head and forepart of the body tilted constantly to one side, both when resting and walking. The tilt was in either direction but was always constant for a given animal; in different mice, the angle varied considerably from almost 0 to 30°. Some mice circled repeatedly in one direction in the home cage, others bobbed their heads and did back‐flips, while others rolled over, always rolling in the same direction.In the hamster, developmental toxicity was seen at (100 and 200 mg/kg/d) or near (50 mg/kg/d) maternally toxic doses but no behavioral alterations were noted and none of the pups were ballooned.The highest dose of dinocap (100 mglkgld during days 7–20) used in the rat study produced mild maternal toxicity (reduced maternal weight gain from day 3 to 10 of gestation), but did not alter the postnatal development of