Neurotoxicity of isoproturon, a substituted phenylurea herbicide, in mice.

Effects of single oral administration of isoproturon (0.5, 1.0 and 2.0 g/kg) on CNS of male mice were studied. At higher doses, spontaneous motor activity (SMA) and forced locomotor activity (FLA) were reduced. Reduction of SMA and FLA was lesser than the reference drug-chlorpromazine hydrochloride (Ch. HCl; 15 mg/kg). Isoproturon, at all doses, potentiated both pentobarbital and barbital-induced sleeping time. At higher doses, potentiation of pentobarbital-induced hypnosis was comparable to Ch.HCl but isoproturon was more effective in inducing hypnosis with barbital. Isoproturon could not protect mice against amphetamine-induced aggregation toxicity. Isoproturon exhibited anticonvulsant activity against both supramaximal electroshock seizures and pentylenetetrazol-induced convulsions. It had no anticonvulsant activity against strychnine but only caused delay in onset of and protection from mortality. At higher doses, anticonvulsant action of isoproturon was comparable to diphenylhydantoin (50 mg/kg) and phenobarbital sodium (100 mg/kg). The study reveals that isoproturon has distinct inhibitory effect on central motor performance and sedative action on CNS. And also it has anticonvulsive and protective actions.

Fetotoxic and teratogenic potential of substituted phenylurea herbicide, isoproturon, in rats.

Effect of isoproturon (0.225, 0.45 and 0.90 g/kg/day) administered (po) from day 6 through 15 of gestation was studied on pregnant rats and their offsprings. There were no distinct clinical signs other than dose-related depression and drowsiness of pregnant rats. None of the animals died due to toxicity of isoproturon. At higher doses, decreased maternal body weight was observed during the advanced stage of pregnancy. The litter size, fetal weight and crown-rump and transumbilical lengths were decreased. There was increase in fetal resorption frequency and the number of fetuses with stunted growth. The compound had no effect on fetal sex ratio. No major visceral and skeletal malformations were observed. The study indicates fetotoxic potential of the compound.

Genotoxic effect of isoproturon (herbicide) as revealed by three mammalian in vivo mutagenic bioassays.

Genotoxic effect of isoproturon was assessed by employing in vivo chromosomal aberration, micronucleus and sperm-shape abnormality assays. A significant dose-responsive mutagenic effect was observed in chromosome aberration and sperm-shape abnormality tests whereas in micronucleus assay the effect was significant only at the highest dose (200 mg/kg). Only the result for the chronic dose and the two different fixation times (6 and 48 hr) were not statistically significant. The results indicate the genotoxic property of isoproturon in mammalian in vivo test system.