title: Application of a source-to-outcome model for the assessment of health impacts from dietary exposures to insecticide residues.
abstract: The paper presents a case study of the application of a "source-to-outcome" model for the evaluation of the health outcomes from dietary exposures to an insecticide, chlorpyrifos, in populations of adults (age 30) and children (age 3). The model is based on publically-available software programs that characterize the longitudinal dietary exposure and anthropometry of exposed individuals. These predictions are applied to a validated PBPK/PD model to estimate interindividual and longitudinal variation in brain and RBC AChE inhibition (key events) and chlorpyrifos concentrations in blood and TCPy in urine (biomarkers of exposure). The predicted levels of chlorpyrifos and TCPy are compared to published measurements of the biomarkers. Predictions of RBC AChE are compared to levels of inhibition associated with reported exposure-related effects in humans to determine the potential for the occurrence of adverse cholinergic effects. The predicted distributions of chlorpyrifos in blood and TCPy in urine were found to be reasonably consistent with published values, supporting the predictive value of the exposure and PBPK portions of the source-to-outcome model. Key sources of uncertainty in predictions of dietary exposures were investigated and found to have a modest impact on the model predictions. Future versions of this source-to-outcome model can be developed that consider advances in our understanding of metabolism, to extend the approach to other age groups (infants), and address intakes from other routes of exposure.
authors.affiliation: The Dow Chemical Company, Midland, MI, USA. pprice@dow.com
authors.forename: Paul S
authors.initials: PS
authors.lastname: Price
authors.forename: Karl D
authors.initials: KD
authors.lastname: Schnelle
authors.forename: Cheryl B
authors.initials: CB
authors.lastname: Cleveland
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Bartels
authors.forename: Paul M
authors.initials: PM
authors.lastname: Hinderliter
authors.forename: Charles
authors.initials: C
authors.lastname: Timchalk
authors.forename: Torka S
authors.initials: TS
authors.lastname: Poet
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D000328:Adult; D015415:Biomarkers / Q000097:blood / Q000652:urine; D002675:Child, Preschool; D004390:Chlorpyrifos / Q000378:metabolism / Q000633:toxicity*; D003198:Computer Simulation; D004032:Diet; D004781:Environmental Exposure; D005506:Food Contamination; D006801:Humans; D007306:Insecticides / Q000378:metabolism / Q000633:toxicity*; D008137:Longitudinal Studies; D018673:Nutrition Policy; D010573:Pesticide Residues / Q000378:metabolism / Q000633:toxicity*; D011237:Predictive Value of Tests; D018570:Risk Assessment / Q000379:methods; D012984:Software
chemical_list: D015415:Biomarkers; D007306:Insecticides; D010573:Pesticide Residues; D000110:Acetylcholinesterase; D004390:Chlorpyrifos