Physiologically-Based Pharmacokinetic / Pharmacodynamic (PBPK/PD) Model for Carbaryl and the PBPK Models for Deltamethrin and Permethrin
If the PBPK or PBPK-PD models under consideration in the current peer review are found to be appropriate for characterizing PK or PD behaviors, they will be used to further refine the risk assessments for these pesticides. In effect, the PBPK or PBPK-PD models will allow for a more rigorous interpretation of how animal toxicity data can be extrapolated to potential effects in humans for each insecticide. The consideration of PBPK or PBPK-PD models requires EPA to critically evaluate not only the structure, parameterization, and coding of these models, but also their scientific credibility for use in human health risk assessments. These evaluation efforts are the purpose of this peer review.
The three insecticides, which are the focus of this review, are currently being evaluated in EPA’s Registration Review process. In other words, the risk assessments for these three insecticides are all in the process of being updated. In typical risk assessments, animal model-derived toxicity values are coupled with pertinent exposure information to calculate risk estimates, which are then compared to an appropriate safety (uncertainty) factor. When risks are identified, EPA can opt to refine the risk assessment with additional data, tools, and techniques. In this case, physiologically-based pharmacokinetic (PBPK) or PBPK-pharmacodynamic (PBPK-PD) models have been developed to allow for more refined consideration of how animal toxicity data can be extrapolated to humans and how differing exposure patterns in humans can impact risk estimates. The focus of this review is to evaluate the individual PBPK or PBPK-PD models for these three insecticides.
URLs/Downloads:EPA to Hold October 12, 2018 Meeting on PBPK/PD Models
External Peer Review of EPA’s Physiologically-based Pharmacokinetic (PBPK) Model for Deltamethrin and Permethrin and PBPK-Pharmacodynamic (PBPK-PD) Model for Carbaryl (PDF,NA pp, 1795 KB, about PDF)