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Dimethyl methyl phosphonate induction of dominant lethal mutations in male mice
Abstract:
The reproductive toxicity of dimethyl methyl phosphonate (DMMP) was studied in the male B6C3F1 mouse. Male mice were treated with 0, 250, 500, 1000, and 2000 mg/kg DMMP by gavage 5 days per week for 13 weeks. After 4, 8 and 12 weeks of treatment the male mice were mated to untreated CD-1 female mice. At the two highest doses (1000 and 2000 mg/kg) the chemical caused a dominant lethal effect (early resorptions). Groups of male mice (at 1000 and 2000 mg/kg), mated after a 15-week recovery period without chemical dosing, had a resorption rate comparable to the control group. After 13 weeks of dosing, the male mice showed no histopathologic changes of the reproductive organs, no abnormalities in sperm concentration or sperm morphology, no evidence for hormone imbalance, no signs of general toxicity, and no effects on the fertilization rate. The male B6C3F1 mouse was less responsive than the male Fischer 344/N rat to the reproductive toxic effects of DMMP.
Insights
Dimethyl methyl phosphonate (DMMP) caused early resorptions in male mice at high doses, indicating reproductive toxicity. Effects were reversible after a recovery period, and mice showed no other reproductive or general toxicity signs.
Area of Science:
- Toxicology
- Reproductive Toxicology
- Environmental Health
Background:
- Dimethyl methyl phosphonate (DMMP) is a chemical compound with potential toxicological implications.
- Understanding the reproductive toxicity of industrial chemicals is crucial for human health risk assessment.
Purpose of the Study:
- To investigate the reproductive toxicity of DMMP in male B6C3F1 mice.
- To determine dose-response relationships and reversibility of potential toxic effects.
Main Methods:
- Male mice were administered varying doses of DMMP (0-2000 mg/kg) via gavage for 13 weeks.
- Mating trials were conducted at different time points during and after treatment.
- Histopathological examination, sperm analysis, hormone level assessment, and general toxicity screening were performed.
Main Results:
- DMMP induced a dominant lethal effect, evidenced by early resorptions, at the highest doses (1000 and 2000 mg/kg).
- Reproductive effects were reversible, with resorption rates returning to control levels after a 15-week recovery period.
- No histopathological changes in reproductive organs, sperm abnormalities, hormone imbalances, or general toxicity were observed after 13 weeks of dosing.
- Male B6C3F1 mice exhibited lower sensitivity to DMMP's reproductive toxicity compared to Fischer 344/N rats.
Conclusions:
- DMMP exhibits dose-dependent reproductive toxicity in male mice, primarily through dominant lethal effects.
- The observed reproductive toxicity is reversible upon cessation of exposure.
- Male B6C3F1 mice are less susceptible to DMMP-induced reproductive toxicity than rats, suggesting species-specific responses.