Handbook of Pesticide Toxicology. Krieger RI, ed., San Diego, CA: Academic Press, 2001 Oct; 2:929-951
This chapter has illustrated a number of current and future applications of pharmacokinetics to assess OP dosimetry, biological response and risk in humans exposed to these insecticides. Pharmacokinetics is concerned with the quantitative integration of absorption, distribution, metabolism and excretion and can be used to provide useful insight into the toxicological responses associated with OP insecticides. Since OP insecticides share a common mode of action through their capability to inhibited AChE activity, it is feasible to develop pharmacokinetic strategies that link quantitative dosimetry with biologically based pharmacodynamic (PD) response modeling. Pharmacokinetic studies that have been conducted with OP insecticides in multiple species, at various dose levels, and across different routes of exposure have provided important insight into in vivo behavior of these OPs. The development and application of pharmacokinetic models capable of describing uptake, distribution, metabolism, and elimination of OP insecticides in humans represent a crucial research element needed for quantitative biomonitoring. In this regard, the successful application of biomonitoring for quantitating OP dose is primarily limited by the lack of this chemical-specific pharmacokinetic data in humans. The development and application of PBPK/PD modeling for OP insecticides represent a unique opportunity to quantitatively assess human health risk and to understand the toxicological implications of known or suspected exposures OPs. Validated PBPK/PD models for OPs can be used to consider the potential variability in human response associated with both interindividual (i.e., age, gender, polymorphism) and extrinsic variability (i.e., exposure routes and rates, single vs. multiple exposures). In conclusion, pharmacokinetics have been successfully utilized to better understand the toxicological implications of human' exposure to OP insecticides. Nonetheless, there is still a significant need to further develop and refine pharmacokinetic models that can be used to accurately assess the risk associated with OP insecticide exposures.
Pharmacodynamics; Pesticides; Pesticides-and-agricultural-chemicals; Organo-phosphorus-compounds; Organo-phosphorus-pesticides
Research Tools and Approaches: Exposure Assessment Methods
Handbook of Pesticide Toxicology
Battelle Memorial Institute, Richland, Washington