Organophosphorus insecticide pharmacokinetics.
Hayes' handbook of pesticide toxicology, 3rd edition. Krieger R, Doull J, Hodgson E, Maibach H, Reiter L, Ritter L, Ross J, Slikker W Jr., van Hemmen J, eds. Boston, MA: Academic Press, 2010 Jan; 2:1409-1433
This chapter has illustrated a number of current and future applications of pharmacokinetics to assess organophosphorus insecticide 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 these insecticides. Since organophosphorus insecticides share a common mode of action through their capability to inhibit 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 organophosphorus insecticides in multiple species, at various dose levels, and across different routes of exposure have provided important insights into the in vivo behavior of these insecticides. The development and application of pharmacokinetic models capable of describing uptake, distribution, metabolism, and elimination of insecticides in humans represent a crucial research element needed for quantitative biomonitoring. In this regard, the successful application of biomonitoring for quantitating dosimetry is primarily limited by the lack of this chemical-specific pharmacokinetic data in humans. The development and application of PBPK/PD modeling for organophosphorus insecticides represent a unique opportunity to quantitatively assess human health risk and to understand the toxicological implications of known or suspected exposures to various insecticides. Validated PBPK/PD models for these insecticides 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 has been successfully utilized to better understand the toxicological implications of human exposure to organophosphorus 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 insecticide exposures.
Pharmacodynamics; Pesticides-and-agricultural-chemicals; Pesticides; Insecticides; Organo-phosphorus-pesticides; Organo-phosphorus-compounds; Biomarkers; Humans; Models; Exposure-assessment; Demographic-characteristics
Krieger-R; Doull-J; Hodgson-E; Maibach-H; Reiter-L; Ritter-L; Ross-J; Slikker-W Jr.; van Hemmen-J
Agriculture, Forestry and Fishing; Research Tools and Approaches: Exposure Assessment Methods
Hayes' handbook of pesticide toxicology, 3rd edition
Battelle Pacific Northwest Laboratories