EPA Science Advisory Panel to Use Chlorpyrifos Data for Improving Health Risk Assessment Exposure Modeling

01/05/2011 -

A panel of independent scientific advisors convened by EPA under the Federal Insecticide, Rodenticide and Fungicide Act is scheduled to meet in February to evaluate a new approach to health risk assessment, using data on chlorpyrifos as a case study. The new approach is believed to offer regulators more refined, more scientifically defensible risk assessments, thus reducing scientific uncertainties and potentially diminishing the use of extreme, worst-case assumptions in regulatory decision-making.

The upcoming science advisory panel review, set for February 15-18, may provide EPA with important guidance for its next health risk assessment of chlorpyrifos, which is currently scheduled for completion in 2011.

The new approach to health risk assessment – known as pharmacokinetic/ pharmacodynamic (PBPK/PD) modeling – provides better information about how pesticides interact with the human body, offering dose-related mathematical projections of how much of the material enters the body, how it is distributed, how rapidly, where and by what processes it is broken down; and how and at what rate the body gets rid of it. This information is particularly helpful in complex regulatory assessments involving different forms of experimental data from different species at different doses via different routes of exposure and also with projections of human exposure from different media (e.g., diet, water, other), and especially when dealing with compounds operating by similar mechanisms of action.

The review panel chose to use chlorpyrifos as a case study for evaluating this more advanced approach to health risk modeling because of the wealth of data that has been developed on the product over many years of research. This dataset includes a well-defined understanding of metabolism and mechanism of action, multiple markers for exposure and effect, a detailed model offering quantitative predictions for the most sensitive markers of exposure (i.e. inhibition of plasma and red blood cell cholinesterases) and actual human data for model calibration and evaluation.

This rich dataset and the PBPK/PD model to interpret it were developed in response to the recommendations of a 2008 science advisory panel review, advocating use of the PBPK/PD approach to enhance previous, draft EPA chlorpyrifos evaluations. The Agency’s prior approach to assessing chlorpyrifos was largely based on results of cholinesterase inhibition in adult laboratory animals as modified by the Agency through the use of default uncertainty factors to address regulatory concerns about individual and interspecies differences and potentially greater susceptibility in certain sub-groups.

At the February meeting, the science advisory panel will be evaluating the feasibility of linking chlorpyrifos PBPK/PD modeling data with the EPA’s current Cumulative and Aggregate Risk Evaluation System (CARES). The chlorpyrifos PBPK/PD model to be considered uses existing regulatory software models for estimating pesticide exposures over time (e.g., CARES, LifeLine, SHEDS). The model projects exposures for three different age groups (adults, 3-yr-olds, and 6-mo-olds). It also includes an analysis of factors that contribute to individual differences in susceptibility and provides a sounder scientific basis for developing age-specific regulatory uncertainty factors.

Read the Federal Register Notice for the FIFRA Science Advisory Panel meeting .

Related: health risk assessment » improving exposure modeling » chlorpyrifos data » SAP » Scientific Advisory Panel » EPA SAP » FIFRA » new data » regulatory process




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