ASSESSMENT OF DEVELOPMENTAL TOXICITY ON THE NEURAL TUBE, CYTO-AND GENOTOXICITY OF CHLORPYRIFOS IN PREGNANT MICE
Miriam Ramzy Riad*, Eman Elazab Beheiry*, Rasha Mohammed El-Shinety*, Ayman Salah El-Seedy**, Amina Tolba Farag***, Shawky Mahmoud Tayel*
*Department of Human Anatomy and Embryology, Faculty of Medicine, University of Alexandria.
**Department of Genetics, Faculty of Agriculture, University of Alexandria.
***Department of Pesticide chemistry and toxicology, Faculty of Agriculture, University of Alexandria.
Background: Studies have shown increasing evidence to suggest an association between environmental exposure to certain agricultural pesticides and adverse reproductive outcomes in women. Chlorpyrifos, an organophosphorus insecticide recommended universally and in Egypt to control various pests, was evaluated for its potential developmental toxicity. Objectives: The aim of this work was to assess the impacts of chlorpyrifos on the developing fetus and the neural tube in particular and detect congenital anomalies, if any and also to clarify the geno- and cytotoxicity effects of chlorpyrifos on pregnant mice. Methods: Virgin female ICR (CD-1) mice, approximately 10 weeks old were mated with adult males .The day the vaginal plug was found was considered day 0 of gestation. Four groups of 30 bred mice each were treated by gavage as follow; 30 mg/kg/day chlorpyrifos (tested group), 40 mg/kg/day sodium arsenite (positive control group), corn oil and distilled water (negative control groups) on days 6–15 of gestation. Maternal observations throughout gestation were reported. Fetal observations, external, visceral and skeletal anomalies of the brain and neural tube were reporded. Metaphase chromosomes were analyzed for genotoxicity using Giemsa staining and mitotic index was measured for cytoxicity. Statistical analysis was done to evaluate the results significance. Results: Dams treated with chlorpyrifos showed signs of cholinergic toxicity including tremors and hyperactivity. Maternal body weight gain, food consumption, absolute organ weights and relative uterus weight were significantly reduced in chlorpyrifos and sodium arsenite groups indicating maternal toxicity. Also increased number of resorptions and dead fetuses and decrease in fetal weights indicating significant fetotoxicity were observed. The observed cranial abnormalities as exencephaly, hydrocephalus and neural tube defects as spina bifida were statistically significant. Chlorpyrifos and sodium arsenite inhibited the mitotic index and increased the frequency of numerical and structural chromosomal aberrations. Conclusions: Chlorpyrifos showed maternal and fetotoxicity at a maternal dose of 30 mg/kg per day, a dose that also produced geno- and cytotoxicity and inhibition of mitotic index. These findings recommend its limited use wether as home insecticide or as agricultural spray.
June 2013