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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 2.4 years, representing the average of independent estimates of 2.5 years (95% Cl, 2.4-2.7) and 2.3 years (95% Cl, 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.

Major fluorinated chemical manufacturers have developed new short-chain per- and polyfluorinated substances with more favorable environmental, health and safety profiles. This study provides the first evaluation of the elimination half-life of perfluorohexanoic acid (PFH)(A) from the blood of humans. PFHxA biomonitoring data were obtained from a recently published study of professional ski wax technicians. These data were analyzed to provide estimates of the apparent half-life of PFHxA from humans, and comparisons were made with kinetic studies of PFHxA elimination from mice, rats and monkeys. The apparent elimination half-life of PFHxA in highly exposed humans ranged between 14 and 49 d with a geomean of 32 d. The half-lives of PFHxA in mice, rats, monkeys and humans were proportional to body weight with no differences observed between genders, indicating similar volumes of distribution and similar elimination mechanisms among mammalian species. Compared to long-chain perfluoroalkyl acid analogs, PFHxA is rapidly cleared from biota. The consistent weight-normalized elimination half-lives for PFHxA in mammalian species indicates that results obtained from animal models are suitable for establishment of PFHxA benchmark dose and reference dose hazard endpoints for use in human risk assessments.

Multimedia mass balance models of chemical fate in the environment have been used for over 3 decades in a regulatory context to assist decision making. As these models become more comprehensive, reliable, and accepted, there is a need to recognize and adopt principles of Good Modeling Practice (GMP) to ensure that multimedia models are applied with transparency and adherence to accepted scientific principles. We propose and discuss 6 principles of GMP for applying existing multimedia models in a decision-making context, namely 1) specification of the goals of the model assessment, 2) specification of the model used, 3) specification of the input data, 4) specification of the output data, 5) conduct of a sensitivity and possibly also uncertainty analysis, and finally 6) specification of the limitations and limits of applicability of the analysis. These principles are justified and discussed with a view to enhancing the transparency and quality of model-based assessments.

Part of urn:nbn:se:su:diva-8571