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Alkylating properties of dichlorvos (DDVP)
Abstract:
Dichlorvos (DDVP) is a methylating agent. In DNA from mice given 1.9 x 10(-6) mol/kg of DDVP, a degree of alkylation of guanine-N-7 amounting to 8 x 10(-13) mol methyl per g DNA, was found. From this, a rate of clearance of 29 hr-1 was estimated. This value is in reasonable agreement with the value (55 hr-1), calculated from published data on the concentration over time of DDVP in the brain after injection of the compound in mice. Applying a risk estimation on humans exposed to DDVP, the genetic risk connected with the methylating activity of DDVP is low or very low. Comparing the mutagenic effectiveness of DDVP with that of methyl methanesulfonate, indicates that DDVP is more effective than expected from reaction kinetic data. The possible contribution of the dichloroacetaldehyde formed in vivo from DDVP has to be evaluated before a complete risk estimate can be made for DDVP.
Insights
Dichlorvos (DDVP) is a methylating agent that showed low genetic risk in mice DNA studies. However, its mutagenic effectiveness requires further evaluation, especially concerning its metabolite dichloroacetaldehyde.
Area of Science:
- Toxicology
- Genetics
- Environmental Health
Background:
- Dichlorvos (DDVP) is an organophosphate insecticide known to be a methylating agent.
- Understanding the genotoxic potential of DDVP is crucial for human health risk assessment.
Purpose of the Study:
- To quantify the DNA alkylation by DDVP in vivo.
- To estimate the clearance rate of DDVP from DNA.
- To assess the genetic risk associated with DDVP exposure in humans.
Main Methods:
- Administration of DDVP to mice at a specific dose (1.9 x 10(-6) mol/kg).
- Quantification of guanine-N-7 alkylation in mouse DNA.
- Estimation of DDVP clearance rate based on DNA adduct levels.
- Comparison of DDVP's mutagenic effectiveness with methyl methanesulfonate.
Main Results:
- A specific level of guanine-N-7 alkylation (8 x 10(-13) mol methyl per g DNA) was detected in mice exposed to DDVP.
- An estimated clearance rate of 29 hr-1 was derived from the DNA alkylation data.
- This clearance rate aligns with previously published data on DDVP brain concentrations.
- The genetic risk to humans from DDVP's methylating activity was assessed as low to very low.
- DDVP demonstrated higher mutagenic effectiveness than predicted by kinetic data.
Conclusions:
- The direct methylating activity of DDVP poses a low genetic risk.
- DDVP's in vivo mutagenic effectiveness may be underestimated by reaction kinetics alone.
- Further investigation into the role of dichloroacetaldehyde, a DDVP metabolite, is necessary for a comprehensive risk assessment.