dinitrobenzenes and Torticollis

Exposure to the fungicide dinocap during gestation produces behavioral abnormalities in the house mouse that are not apparent at birth but become obvious at weaning. Pregnant mice (CD-1) were exposed on Days 7 to 16 of gestation to dinocap at 0, 6, 12, or 25 mg/kg/day and the postnatal behavioral development of the offspring was assessed. Torticollis (head-tilting) appears in the treated offspring at 3 weeks of age (4.4% at 12 and 25.3% at 25 mg/kg/day) and, during a test of swimming ability, many of the mice (6.8% at 12 and 47.2% at 25 mg/kg/day) sink below the surface or are unstable and swim on their side in the water. These behavioral abnormalities are the result of agenesis of the otoliths in the inner ears. These were the only developmental defects noted in the 12 mg/kg/day dosage group. In this group 4.4% of the mice displayed torticollis, 9.2% did not swim normally, 19% were missing one or more whole otoliths (7.7% were missing all four otoliths), and partial agenesis of the crystalline material was seen in an additional 11.6% of the mice. The frequency of behavioral and inner ear defects increased in the higher dosage group, but the order of sensitivity of the effects did not change.

Topics: Animals; Dinitrobenzenes; Dose-Response Relationship, Drug; Female; Fungicides, Industrial; Maternal-Fetal Exchange; Mice; Motor Activity; Nitrobenzenes; Otolithic Membrane; Pregnancy; Saccule and Utricle; Swimming; Torticollis

Technical-grade dinocap, a complex-mixture fungicide, is teratogenic in the CD-1 mouse, causing cleft palate and otolith defects. In this study we compared the developmental toxicities of 2,4-dinitro-6-(1-methylheptyl)phenyl crotonate and 2,6-dinitro-4-(1-methylheptyl)phenyl crotonate, model isomers of the major active ingredients of technical dinocap, to the known teratogenicity of the technical compound. Individual isomers, both isomers combined, or technical dinocap were administered to pregnant mice on days 7-16 of gestation. Some dams were killed at term and litters were removed, dead fetuses and resorptions were counted, and live fetuses were weighed and preserved in Bodian's fixative for examination for cleft palate. Other treated dams were allowed to give birth: postnatal viability and growth, development of swimming behavior, and otolith formation were evaluated. As in previous studies, technical-grade dinocap caused cleft palate and weight deficits in fetuses at term and increased neonatal mortality and abnormal swimming behavior, torticollis, and deficient otolith formation in surviving pups. Neither of the purified isomers exhibited any developmental toxicity when administered under identical conditions. Thus, it is concluded that these isomers are not the active teratogenic component(s) in technical-grade dinocap.

Topics: Animals; Dinitrobenzenes; Female; Fetal Death; Fetal Resorption; Insecticides; Isomerism; Mice; Motor Activity; Nitrobenzenes; Otolithic Membrane; Pregnancy; Swimming; Teratogens; Torticollis

The 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 degrees. 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.

Topics: Animals; Animals, Newborn; Behavior, Animal; Cleft Palate; Cricetinae; Dinitrobenzenes; Dose-Response Relationship, Drug; Female; Litter Size; Mice; Nitrobenzenes; Pregnancy; Rats; Species Specificity; Teratogens; Torticollis