Physiologically based pharmacokinetic modeling of organophosphorus and carbamate pesticides.
Toxicology of Organophosphate & Carbamate Compounds. Gupta RC, ed., Boston, MA: Academic Press, 2006 Jan; :103-125
This chapter has illustrated the applications of PBPK/PD modeling to assess OP and potentially CM 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 insight into the toxicological responses associated with these insecticides. Since OP and CM 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 PD response modeling. Pharmacokinetic studies that have been conducted in multiple species, at various dose levels, and across different routes of exposure have provided important insight into the in vivo behavior of these insecticides. The development and application of PBPK/PD modeling for these insecticides represents a unique opportunity to quantitatively assess human health risk and to understand the toxicological implications of known or suspected exposures. Validated PBPK/PD models can be used to consider the potential variability in human response associated with both interindividual (i.e., age, gender, and polymorphism) and extrinsic variability (i.e., exposure routes and rates, and single vs multiple exposures).
Pharmacodynamics; Organo-phosphorus-pesticides; Exposure-levels; Blood-samples; Gas-chromatography; Models; Insecticides; Organo-phosphorus-compounds; Neurotoxic-effects; Neurotoxicity; Neurotoxins; Acute-exposure; Brain-disorders; Brain-function
Research Tools and Approaches: Exposure Assessment Methods
Toxicology of Organophosphate & Carbamate Compounds
Battelle Memorial Institute, Richland, Washington