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.

Effects of oral exposure of synthetic pyrethroid, cypermethrin on the behavior of F1-progeny in mice.

Cyermethrin, a type II synthetic pyrethroid insecticide, was evaluated through assessment of the behavioral development of F1-progeny of mice. Groups each of 30 male and 30 female ICR (CD-l) mice, as F0-generation, were given 0, 2.5, 5, and 10mg/kg/day cypermethrin in corn oil orally for 4 weeks/5 days in a week before mating. Behavioral endpoints of motor reflexes, motor coordination, and activity were evaluated in F1-progeny. Clinical signs of toxicity including salivation, hyperactivity, and tremors which attributed to cypermethrin were observed in the F0-mice treated with 10mg/kg/day. A significant delay in the development of pinna detachment, down appearance, and eye opening of 48, 59, and 27 pups (47, 64, and 39%, respectively) was observed in the high dose group. Reduction of body weight became significantly evident only for F0-females either during treatment or gestation and lactation periods for the high dose group. Significant differences in the development of reflexes, swimming ability, and open-field activity were evident in the offspring for the 10mg/kg/day dose group compared to the control group. These results show that cypermethrin at dose level of 10mg/kg/day can induce a significant risk to the offspring following treatment of F0-mice before mating. The NOAEL obtained in this study for the effects of cypermethrin on the development of the F1-progeny is 5mg/kg/day.

Assessment of reproductive toxicity of orally administered technical dimethoate in male mice.

The effect of organophosphate insecticide dimethoate at three dosage levels (7, 15, and 28 mg/kg/day) on male reproduction in mice was studied. Dimethoate was given orally by gavage to male mice for 20 days before mating with untreated females. Signs of cholinergic effects were observed in the 15 and 28 mg/kg/day treated groups. Brain and skeletal muscle acetylcholinesterase activities were inhibited in both the middle and high dose groups. Dimethoate was associated with a decreased number of implantations and live fetuses, and an increased number of dead and early resorptions at 28 mg/kg/day treated group. The percent morphologically normal spermatozoa were unaffected in any of dose groups. However, sperm production and percent motile sperm were decreased in the 15 and 28 mg/kg/day treated groups compared to the control. Histological changes in testis were observed in the middle and high treated groups. The current study demonstrated the adverse effects of dimethoate on the reproductive performance of male mice and pregnancy outcomes following mating with untreated female mice at dose levels of 15 and 28 mg/kg/day. The No Observed Effect Level (NOEL) in the present study for reproductive performance was 7 mg/kg/day.

Developmental toxic effects of antifungal flusilazole administered by gavage to mice.

BACKGROUND: The developmental toxicity of flusilazole was studied in CD-1 mice after oral administration. METHODS: Pregnant mice were given flusilazole at doses of 0 (corn oil), 10, 20, and 40 mg/kg/day, by gavage, on gestational days (GD) 6-15. RESULTS: Maternal toxicity, as evidenced by reduction in body weight gain and signs of toxicity, was observed at the middle- and high-dose groups. No significant incidence of resorptions or death was observed in any of dose groups. There was a pronounced reduction in fetal weight, which was significantly lower than control from 20 and 40 mg/kg/day. There was no significant increase in the incidence of fetuses with external or visceral malformations in any of dose groups, but there was a significant increase in the incidence of skeletal malformations was observed at 20 and 40 mg/kg/day. CONCLUSIONS: The results of this study reported marked maternal toxicity, growth retardation, and skeletal abnormalities in the mid- and high-dose groups. It seems likely that marked maternal toxicity contributed to the observed alterations in fetal growth retardation and skeletal development. The no-observed-effect level in the present study for maternal and developmental toxicity was 10 mg/kg/day.

Embryotoxicity of oral administered chlorothalonil in mice.

BACKGROUND: Chlorothalonil (2,4,5,6-tetrachloroisophthalonitril), the nephrotoxic fungicide, was examined for its potential to produce developmental toxicity in mice after oral administration. METHODS: Pregnant ICR (CD-1) mice were given sublethal doses of 0 (corn oil), 100, 400, and 600 mg/kg/day chlorothalonil by gavage on gestation days (GD) 6-15. RESULTS: Maternal effects in 400 and 600 mg/kg/day dose groups included signs of toxicity such as weakness and depression in the maternal activity, and reduction in body weight and weight gain. No maternal toxicity was apparent in the 100 mg/kg/day dose group. Maternal exposure to chlorothalonil during organogenesis significantly affected the number of live fetuses, early resorption, and mean fetal weight in the 400 and 600 mg/kg/day dose groups. No external, visceral, and skeletal abnormalities were observed among any of the treated groups compared to the control. CONCLUSIONS: On the basis of the present results chlorothalonil can produce clinical signs of toxicity and fetotoxicity without teratogenic effects at 400 and 600 mg/kg/day dose groups.

Developmental toxicity of orally administered technical dimethoate in rats.

BACKGROUND: Dimethoate (O,O-dimethyl-S-(N-methylcarbamoyl-methyl) phosphorodithioate), an organophosphate insecticide, was examined for its potential to produce developmental toxicity in rats after oral administration. METHODS: Pregnant Fischer 344 rats were given sublethal doses of 0 (corn oil), 7, 15, and 28 mg/kg/day dimethoate by gavage on gestation days (GD) 6-15. Maternal effects in 15 and 28 mg/kg/day dose groups included cholinergic signs such as tremors, diarrhea, weakness, and salivation, and depression in the maternal and fetal brain acetylcholinesterase (AChE) activities. Other maternal toxicity that included reduction in body weight and feed consumption was observed only in the treated group of 28 mg/kg/day. No maternal toxicity was apparent in the 7 mg/kg/day dose group. RESULTS: Maternal exposure to dimethoate during organogenesis significantly affected the number of live fetuses, early resorption, and mean fetal weight in the 28 mg/kg/day dose group. No external, visceral, and skeletal abnormalities were observed in any of the treated groups compared to the control. CONCLUSIONS: On the basis of the present results dimethoate can produce clinical signs of toxicity and significant inhibition of the maternal and fetal AChE activities in dose groups of 15 and 28 mg/kg/day and showed fetotoxicity without teratogenic effects at 28 mg/kg/day.

Effects of permethrin given before mating on the behavior of F1-generation in mice.

Permethrin, a type I synthetic pyrethroid insecticide, was evaluated through assessment of the behavioral development of F1 progeny of mice. Groups each of 30 male and 30 female ICR (CD-1) mice, as F0-generation, were given 0, 4.9, 9.8, and 19.6 mg/kg/d permethrin by gavage for 4 weeks before mating. Behavioral endpoints of motor reflexes, motor coordination, and activity were evaluated in F1 progeny. Clinical signs of toxicity including salivation, hyperactivity, and liquid feces which attributed to permethrin were observed in the F0-mice treated with 9.8 and 19.6 mg/kg/d. Reduction of body weight became evident only during gestation and lactation periods for the middle and high dose groups. Significant differences in the development of reflexes, swimming ability, and open field activity were evident in the offspring for the 9.8 and 19.6 mg/kg/d dose groups compared to the control group. These results show that permethrin at dose levels of 9.8 and 19.6 mg/kg/d can induce a significant risk to the offspring following treatment of F0-mice before mating. The NOEL obtained in this study for the effects of permethrin on the development of the F1-progeny is 4.9 mg/kg/d.

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.