title: Derivation of human Biomonitoring Guidance Values for chlorpyrifos using a physiologically based pharmacokinetic and pharmacodynamic model of cholinesterase inhibition.
abstract: A number of biomonitoring surveys have been performed for chlorpyrifos (CPF) and its metabolite (3,5,6-trichloro-2-pyridinol, TCPy); however, there is no available guidance on how to interpret these data in a health risk assessment context. To address this gap, Biomonitoring Guidance Values (BGVs) are developed using a physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) model. The PBPK/PD model is used to predict the impact of age and human variability on the relationship between an early marker of cholinesterase (ChE) inhibition in the peripheral and central nervous systems [10% red blood cell (RBC) ChE inhibition] and levels of systemic biomarkers. Since the PBPK/PD model characterizes variation of sensitivity to CPF in humans, interspecies and intraspecies uncertainty factors are not needed. Derived BGVs represent the concentration of blood CPF and urinary TCPy associated with 95% of the population having less than or equal to 10% RBC ChE inhibition. Blood BGV values for CPF in adults and infants are 6100 ng/L and 4200 ng/L, respectively. Urinary TCPy BGVs for adults and infants are 2100 μg/L and 520 μg/L, respectively. The reported biomonitoring data are more than 150-fold lower than the BGVs suggesting that current US population exposures to CPF are well below levels associated with any adverse health effect.
authors.affiliation: The Dow Chemical Company, Midland, MI, United States. Electronic address: smarnold@dow.com.
authors.forename: Scott M
authors.initials: SM
authors.lastname: Arnold
authors.affiliation: Dow AgroSciences Ltd., Milton Park, Abingdon, United Kingdom.
authors.forename: Alistair
authors.initials: A
authors.lastname: Morriss
authors.affiliation: Dow AgroSciences, Indianapolis, IN, United States.
authors.forename: Joseph
authors.initials: J
authors.lastname: Velovitch
authors.affiliation: Dow AgroSciences, Indianapolis, IN, United States.
authors.forename: Daland
authors.initials: D
authors.lastname: Juberg
authors.affiliation: The Dow Chemical Company, Midland, MI, United States.
authors.forename: Carol J
authors.initials: CJ
authors.lastname: Burns
authors.affiliation: The Dow Chemical Company, Midland, MI, United States.
authors.forename: Michael
authors.initials: M
authors.lastname: Bartels
authors.affiliation: Dow AgroSciences Ltd., Milton Park, Abingdon, United Kingdom.
authors.forename: Manoj
authors.initials: M
authors.lastname: Aggarwal
authors.affiliation: Summit Toxicology, LLP, Richland, WA, United States.
authors.forename: Torka
authors.initials: T
authors.lastname: Poet
authors.affiliation: Summit Toxicology, LLP, Lyons, CO, United States.
authors.forename: Sean
authors.initials: S
authors.lastname: Hays
authors.affiliation: The Dow Chemical Company, Midland, MI, United States.
authors.forename: Paul
authors.initials: P
authors.lastname: Price
mesh_terms: D000328:Adult; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D004390:Chlorpyrifos / Q000378:metabolism* / Q000493:pharmacokinetics; D002800:Cholinesterase Inhibitors / Q000378:metabolism* / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D004784:Environmental Monitoring / Q000379:methods* / Q000592:standards; D006801:Humans; D007223:Infant; D008954:Models, Biological; D051381:Rats
chemical_list: D015415:Biomarkers; D002800:Cholinesterase Inhibitors; D004390:Chlorpyrifos
keywords: Acetylcholinesterase inhibition; Biomonitoring; Biomonitoring Guidance Value; Chlorpyrifos; Physiologically based pharmacokinetic/pharmacodynamic model; Risk assessment