1 / 5

Quantitative Assessment of Sensitivity and Variability in Humans: Modeling Low Dose Exposure to Chlorpyrifos Residues

This study utilizes a source-to-outcome model to evaluate the effects of low dose exposure to dietary residues of chlorpyrifos on cholinesterase inhibition in humans. It assesses variability in both exposure and response, including sensitivity in different age groups. The findings provide valuable insights for risk assessment.

leanos
Download Presentation

Quantitative Assessment of Sensitivity and Variability in Humans: Modeling Low Dose Exposure to Chlorpyrifos Residues

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Regulatory Sciences and Government Affairs Quantitative Assessment of Sensitivity and Variability in Humans: Modeling the Effects of Low Dose Exposure to Dietary Residues of Chlorpyrifos Daland R. Juberg, Dow AgroSciences Paul Price, The Dow Chemical Company May 4, 2011

  2. Background • ACC/LRI request for proposals to use science to advance risk assessment (2007) • Goal: replace safety factors with quantitative predictions of adverse effects • Leverage extensive knowledge on chlorpyrifos • Project expanded in 2010 to address new data on variation in human metabolism • Basis for EPA SAP (2011)

  3. Chlorpyrifos • Widely used active ingredient in insect control products for agriculture (registered in 1965; 100 countries globally) • Extensive toxicological database including: • Full toxicological database for global registrations • Occupational exposure and health monitoring data • Epidemiology studies • Toxicological mechanism and endpoint upon which human exposure limits are based is cholinesterase inhibition

  4. What was Done? • Source-to-outcome model that evaluates the relationship between dietary residues in food and impact on cholinesterase inhibition (ChEI) in exposed populations. Based on combined models: • Dietary model estimates daily dose from dietary residues • PBPK/PD model measures changes in ChEI from oral exposure • The effort is an example of the upstream ‘obligatory perturbation’ concept described in the NAS Toxicity in the 21st Century

  5. Advancements in Risk Assessment • Assessed variability in both exposure (variation of residue levels across foods and variation in individual’s dietary consumptions) and response (variation in physiology and metabolism) • Evaluated response to the range of actual human exposures • Assessed human sensitivity in multiple age groups (infants, children, adults) • Background rates of the apical effects did not prevent the determination of a population threshold for the key event (AChEI) and all subsequent effects of chlorpyrifos

More Related