title: Calculation of chemical elimination half-life from blood with an ongoing exposure source: the example of perfluorooctanoic acid (PFOA).
abstract: Determination of the chemical clearance rate from human blood is a critical component of toxicokinetic exposure assessment. Analysis of temporal biomonitoring data without consideration of ongoing exposure results in calculation of apparent elimination half-life values that are longer than the intrinsic value. The intrinsic elimination half-life is solely a function of the rate of elimination while the apparent elimination half-life reflects the processes of both elimination and ongoing exposure. Confusion between intrinsic and apparent half-life values can lead to misinterpretation of biomonitoring data and can result in exaggerated predictions in subsequent modeling efforts. This work provides a review of the first-order equations that have been developed to calculate intrinsic and apparent half-life values and the potential bias that can result from confusing these two values. Published human biomonitoring data for perfluorooctanoic acid (PFOA) are analyzed using these equations to provide examples of low, medium and high bias in determination of the intrinsic elimination half-life from plasma or serum, the components of blood typically analyzed for PFOA. An approach is also provided to estimate the extent of exposure reduction that is indicated by declining longitudinal or cross-sectional biomonitoring data. Based on the evaluation methodology presented in this work, the intrinsic elimination half-life of PFOA in humans is 2.4years, representing the average of independent estimates of 2.5years (95% CI, 2.4-2.7) and 2.3years (95% CI, 2.1-2.4). The declining concentration of PFOA in blood of the general USA adult population represents an estimated exposure reduction of 20-30% over the period 1999-2008.
authors.affiliation: DuPont Haskell Global Centers for Health and Environmental Sciences, S320/214, P.O. Box 50, Newark, DE 19714-0050, United States. Electronic address: Mark.H.Russell@dupont.com.
authors.forename: Mark H
authors.initials: MH
authors.lastname: Russell
authors.affiliation: DuPont Central Research & Development, Experimental Station, E320/314, Rt 141 and Henry Clay, Wilmington, DE 19880, United States.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Waterland
authors.affiliation: Department of Applied Environmental Science, Stockholm University, Svante Arrhenius väg 8, SE-10691 Stockholm, Sweden.
authors.forename: Fiona
authors.initials: F
authors.lastname: Wong
mesh_terms: D000328:Adult; D002210:Caprylates / Q000493:pharmacokinetics*; D003430:Cross-Sectional Studies; D004784:Environmental Monitoring; D005466:Fluorocarbons / Q000493:pharmacokinetics*; D006207:Half-Life; D006801:Humans
chemical_list: D002210:Caprylates; D005466:Fluorocarbons; C023036:perfluorooctanoic acid
keywords: Background exposure; Elimination; Half-life; Perfluorooctanoic acid