Amina T. Farag

Developmental toxicity study of chlorpyrifos in rats.

Chlorpyrifos (O,O-diethyl-O-(3,5,6-trichloro-2-pyridyl)-phosphorothioate) was evaluated for potential developmental toxicity. Groups of 30 bred female Fischer 344 rats were given 0, 5, 15, and 25mg/kg per day by gavage on gestation days 6-15; the fetuses were evaluated on gestation day 21. Clinical signs of toxicity attributed to chlorpyrifos were noted in dams receiving 15 and 25mg/kg per day. Maternal effects in these groups also included depressed body weight and acetylcholinesterase activity. Fetal weight and viability were decreased, and fetal death and early resorption were increased at the 25mg/kg per day maternal dose. Visceral, skeletal, and external variations were also increased in this group. Chlorpyrifos showed fetotoxic and teratogenic effects at a maternal dose of 25mg/kg per day, a dose that also produced maternal toxicity.

Chlorpyrifos induced reproductive toxicity in male mice.

The reproductive toxicity of the insecticide chloropyrifos was studied in male mice. Adult male mice were treated by gavage with chloropyrifos at doses of 0, 5, 15, and 25mg/kg-d for 4 weeks before mating with untreated females. Signs of cholinergic effects were observed in the 15 and 25mg/kg-d treated groups. Brain and skeletal muscle acetylcholinesterase activity was inhibited in the same groups. Chloropyrifos treatment was associated with a decreased number of live fetuses, and an increased number of dead fetuses at 25mg/kg-d. The number of early resorption was decreased in both 15 and 25mg/kg-d treated groups. The percent morphologically normal spermatozoa were affected in 15 and 25mg/kg-d dose groups; however, sperm motility and count were decreased in the same treated groups compared to the control. Histologic examination of brain revealed histological abnormalities in the middle and high groups. Dose related histologic changes, including degeneration of muscle fibers, were observed in the muscles of male mice treated with all the doses of chloropyrifos. The current study demonstrated adverse effects of male chloropyrifos exposure on pregnancy outcome with effects on sperm parameters at 15 and 25mg/kg-d.

REPRODUCTIVE TOXICOLOGY OF ACEPHATE IN MALE MICE

The reproductive toxicity of the insecticide acephate was studied in male mice. Adult male mice were treated by gavage with acephate at doses of 0, 7, 14, and 28 mg/kg/day for 4 weeks before mating with untreated females. Signs of cholinergic effects were observed in the 28 mg/kg/day group. Brain and skeletal muscle acetylcholinesterase activity was inhibited only in this group. Acephate treatment was associated with a decreased number of implantations and live fetuses, and an increased number of early resorptions at 28 mg/kg/day. The percent morphologically normal spermatozoa was unaffected in all dose groups; however, sperm motility and count were decreased in the 14 and 28 mg/kg/day groups compared to the control. Histologic examination of brain did not reveal any abnormalities. Dose related histologic changes, including degeneration of muscle fibers, were observed in the muscles of male mice treated with any of the doses of acephate. The current study demonstrated adverse effects of male acephate exposure on pregnancy outcome with effects on sperm parameters at 14 and 28 mg/kg/day.

Developmental toxicity of acephate by gavage in mice

Acephate (O,S - dimethyl acetyl phosphoramidothioate), an organophosphate insecticide, was evaluated for its potential to produce developmental toxicity in mice after oral administration. Pregnant ICR (CD-1) mice were given sublethal doses of 0 (distilled water), 7, 14, and 28 mg/kg/day acephate by gavage on Gestation Days 6 through 15. Maternal effects in the 28 mg/kg/day dose group included cholinergic signs, decreased body weight at 15 and 18 days of gestation, and decreased absolute and relative brain weight. Placental weight was also decreased and liver weight was increased in the high dose group. Absolute and relative brain weight was decreased in the 14 mg/kg/day group. No maternal effects were apparent in the 7 mg/kg/day dose group. Maternal exposure to acephate during organogenesis significantly affected the number of implantations, number of live fetuses, number of early resorptions, mean fetal weight, and the incidence of external and skeletal malformations in the 28 mg/kg/day dose group. No visceral malformations were observed. On the basis of the present results acephate showed maternal and developmental toxicity at 28 mg/kg/day.

Evaluation of male-mediated reproductive toxic effects of methamidophos in the mouse.

The reproductive toxicity of the insecticide methamidophos was studied in male mice. Adult male mice were treated by gavage with methamidophos at doses of 0, 1, 2 and 3 mg kg−1 day−1 for 4 weeks before mating with untreated females. Brain and skeletal muscle acetylcholinesterase activity was inhibited in the middle‐ and high‐treated groups. Methamidophos treatment was associated with a decreased number of live foetuses and an increased number of dead and resorption foetuses at 2 and 3 mg kg−1 day−1 treated groups. The per cent morphologically normal spermatozoa were affected in the 2 and 3 mg kg−1 day−1 dose groups; however, sperm motility and count were decreased in the same treated groups compared to the control. Histological examination of brain, muscles, testes and epididymis revealed histological abnormalities in a dose‐dependent manner. The current study demonstrated adverse effects of male methamidophos exposure on pregnancy outcome with effects on sperm parameters at 2 and 3 mg kg−1 day−1.

Scanning electron microscopic study of the effect of chlorpyrifos on the developing neural tube in comparison with Arsenic in mouse embryo

Abstract Background Arsenic is an important environmental toxicant which is usually found in drinking water in inorganic form. Arsenic exposure in pregnant mice causes neural tube defects (NTDs). Chlorpyrifos, an organophosphorus insecticide, recommended universally and in Egypt to control various pests, was evaluated for its potential developmental toxicity. Studies have shown increasing evidence to suggest an association between environmental exposure to this agricultural pesticides and adverse reproductive outcomes. The hypothesis tested in this investigation is chlorpyrifos causes significant defects on the developing central nervous system compared to the proven Arsenic. Objectives The aim of this work was to assess congenital malformations induced by the organophosphorus insecticide chlorpyrifos on the neural tube and brain development in comparison with the positive control Arsenic. 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. It consisted of 320 mice. They were subdivided into four groups of 80 bred mice each. Each group was divided into 4 subgroups, and 20 mice per each were treated by gavage as follows: 30 mg/kg/day chlorpyrifos (tested group), 40 mg/kg/day sodium Arsenite (positive control group), and corn oil and distilled water (negative control groups) on days 6–15 of gestation. Maternal observations throughout gestation were reported. In each subgroup the mice proved to be pregnant were sacrificed on gestational days; GD 10, 11, 12 and 16. The day of scarification was determined according to the neural tube developmental stages. The conceptus extraction was done and their number reported to be subjected to the SEM study. After mice scarification, the uteri were opened and a total of 30 embryos and fetuses, randomly selected from each subgroup were processed for scanning electron microscopy investigating the neural tube developmental defects. Results CPF ingested by gravid mice at dose of 30 mg/kg/day started from 6th day of gestation proved to produce NTDs as compared to Arsenite. Conclusion Neural tube defects are due to chlorpyrifos that may directly influence brain cell replication and differentiation.