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Dominant lethal studies with paraquat and diquat in male CD-1 mice
Abstract:
The herbicides paraquat and diquat were tested for dominant lethal activity in male CD-1 mice. No mutagenic effects were detected on any stage of spermatogenesis in treated males if these compounds were administered orally up to 4 mg paraquat/kg/body weight/day of 10 mg diquat/kg/body weight/day for 5 days. There was no increase in the number of post-implantation losses as shown by the number of females with one or more early deaths or number of early deaths/pregnancy or the number of early deaths/total implants/pragnancy. There was no evidence of pre-implantation losses as indicated by the total implants/pregnant female. There was no anti-fertility effect on the treated males as measured by the pregnancy frequency or successful mating frequency. The lack of dominant lethal effect was not due to particular insensitivity of the animals used since such effects were amply demonstrated in mice doses orally on 5 days with ethyl methanesulphonate at 100 mg/kg/body weight/day, or intraperitoneally on one day with cyclophosphamide at 200 mg/kg/body weight.
Insights
Paraquat and diquat herbicides showed no dominant lethal effects or anti-fertility impacts in male mice during a 5-day oral administration study. These findings indicate a lack of mutagenic activity for these common agricultural chemicals.
Area of Science:
- Toxicology
- Environmental Health
- Reproductive Toxicology
Background:
- Paraquat and diquat are widely used herbicides.
- Assessing the reproductive toxicity and mutagenicity of herbicides is crucial for environmental and human health risk assessment.
- Dominant lethal assays are standard methods for evaluating genotoxic effects on germ cells.
Purpose of the Study:
- To investigate the dominant lethal activity of paraquat and diquat in male CD-1 mice.
- To determine if these herbicides induce mutagenic effects on spermatogenesis.
- To evaluate potential anti-fertility effects of paraquat and diquat exposure.
Main Methods:
- Male CD-1 mice were administered paraquat (up to 4 mg/kg/day) or diquat (up to 10 mg/kg/day) orally for 5 consecutive days.
- Reproductive parameters assessed included post-implantation loss, pre-implantation loss, pregnancy frequency, and mating success.
- Positive controls (ethyl methanesulfonate and cyclophosphamide) were used to validate the assay sensitivity.
Main Results:
- No significant increase in post-implantation losses (early deaths) was observed in females mated with treated males.
- No evidence of pre-implantation losses was detected, as indicated by total implants per pregnant female.
- Pregnancy and mating frequencies remained unaffected, suggesting no anti-fertility effects in treated males.
- The assay sensitivity was confirmed by positive results in control groups treated with known mutagens.
Conclusions:
- Paraquat and diquat do not exhibit dominant lethal activity in male CD-1 mice under the tested oral dosage and duration.
- These herbicides do not appear to cause mutagenic effects on spermatogenesis or possess anti-fertility properties in male mice.
- The study provides evidence for the lack of genotoxic and reproductive toxicity of paraquat and diquat in the male germline of mice.