Evaluation of the genotoxicity induced by the fungicide fenarimol in mammalian and plant cells by use of the single-cell gel electrophoresis assay.

Fenarimol, a systemic pyrimidine carbinol fungicide, is considered to be not genotoxic or weakly genotoxic, although the available toxicological data are controversial and incomplete. Our results obtained in vitro with leukocytes of two different rodent species (rat and mouse) show that fenarimol affects DNA, as detected by the single-cell gel electrophoresis (SCGE, Comet) assay. This fungicide is able to induce DNA damage in a dose-related manner, with significant effectiveness at 36 nM, but without significant interspecies differences. Simultaneous exposure of rat leukocytes to fenarimol (36-290 nM) and a model genotoxic compound (50 microg/ml bleomycin) produced a supra-additive cytotoxic and genotoxic effect. This supports previous findings suggesting possible co-toxic, co-mutagenic, cancer-promoting and co-carcinogenic potential of fenarimol, and modification of the effects of other xenobiotics found to be influenced by this agrotoxic chemical, with consequent different toxicological events. The potential for DNA strand breaks to act as a biomarker of genetic toxicity in plants in vivo was also considered, in view of the fact that higher plants represent reliable sensors in an ecosystem. Significant DNA breakage was observed in the nuclei of Impatiens balsamina leaves after in vivo treatment with fenarimol (145 nM, 1h). More than 50% of the cells showed such DNA damage.

Biological monitoring of embrio-fetal exposure to methamidophos or chlorothalonil on rat development.

Maternal exposure to pesticides during the pre-implantation and very early post-implantation periods of pregnancy is correlated with numerous adverse effects on the offspring and in reproductive parameters like an increase in resorption, a decrease in fetal survival and weight, and teratogenic effects. Although the epidemiological evidence is inconclusive as regards the risk of the adverse outcome of pregnancy and developmental toxicity events, the use of biomarkers in exposure assessment may contribute to recognizing a potential health impairment. The present study evaluated the influence of prenatal oral exposure to an insecticide (1.0 mg methamidophos/kg) or a fungicide (200.0 mg chlorothalonil/kg) during gestation days 1 to 6 on maturational and behavioral aspects of offspring development of rats. The pesticides did not affect the body weight gain of dams and offspring, nor did the exposure affect the weight of gravid uterus, fetus, placenta and ovary. There were no observed alterations in the swimming behavior tested at postnatal days 7, 14 and 21, but the pesticides interfered with physical and maturational development landmarks of offspring according to age, showing subtle effects on behavioral and physical development. These findings show the importance of categorizing developmental effects, establishing the relationship between age and important performances, to recognize potential impacts on human populations.

Relevance of developmental testing of exposure to methamidophos during gestation to its toxicology evaluation.

The organophosphate insecticide (OP) are known to be able to promote cholinergic toxicity related to neurobehavioral findings. The measures of cholinesterase activity are the most common index of its action. The influence was evaluated, of the OP methamidophos (1.0 mg/kg), by oral exposure during gestational organogenesis of rats, on maturational and behavioral aspects of offspring development. This dose did not promote evidence of maternal toxicity. The pesticide did not affect body weight gain of the dams and offspring, but interfered with the offspring's physical and maturational development landmarks according to age. The behavioral performance of the offspring with or without a pharmacological challenge was tested at different postnatal days (pnd 14, 21 and 40) in an open-field apparatus. The results showed a large standard deviation that prejudiced the conclusions. There were no observed alterations in the swimming behavior tested also at pnd 7, 14 and 21. As long as the obtained results showed some subtle effects on rat development, the data, as possible additional effect biomarkers for risk analysis, will aid further studies of the embryo-feto-toxic potential of OP exposure.