A Generic Pharmacokinetic Model for Quantifying Mother-to-Offspring Transfer of Lipophilic Persistent Environmental Chemicals.

Autor:	Kapraun DF; Center for Public Health and Environmental Assessment, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27709, USA., Zurlinden TJ; Center for Public Health and Environmental Assessment, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27709, USA., Verner MA; Department of Occupational and Environmental Health, School of Public Health, Université de Montréal, Montreal, Quebec H3T 1A8, Canada.; Centre de Recherche en Santé Publique, Université de Montréal and CIUSSS Du Centre-Sud-de-l'île-de-Montréal, Montreal, Quebec H3N 1X7, Canada., Chiang C; Center for Public Health and Environmental Assessment, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27709, USA., Dzierlenga MW; Center for Public Health and Environmental Assessment, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27709, USA., Carlson LM; Center for Public Health and Environmental Assessment, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27709, USA., Schlosser PM; Center for Public Health and Environmental Assessment, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27709, USA., Lehmann GM; Center for Public Health and Environmental Assessment, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27709, USA.
Jazyk:	angličtina
Zdroj:	Toxicological sciences : an official journal of the Society of Toxicology [Toxicol Sci] 2022 Sep 24; Vol. 189 (2), pp. 155-174.
DOI:	10.1093/toxsci/kfac084
Abstrakt:	Lipophilic persistent environmental chemicals (LPECs) can accumulate in a woman's body and transfer to her developing child across the placenta and via breast milk. To assess health risks associated with developmental exposures to LPECs, we developed a pharmacokinetic (PK) model that quantifies mother-to-offspring transfer of LPECs during pregnancy and lactation and facilitates internal dosimetry calculations for offspring. We parameterized the model for mice, rats, and humans using time-varying functions for body mass and milk consumption rates. The only required substance-specific parameter is the elimination half-life of the LPEC in the animal species of interest. We used the model to estimate whole-body concentrations in mothers and offspring following maternal exposures to hexachlorobenzene (HCB) and 2,2',4,4',5,5'-hexachlorobiphenyl (PCB 153) and compared these with measured concentrations from animal studies. We also compared estimated concentrations for humans to those generated using a previously published human LPEC PK model. Finally, we compared human equivalent doses (HEDs) calculated using our model and an allometric scaling method. Estimated and observed whole-body concentrations of HCB and PCB 153 in offspring followed similar trends and differed by less than 60%. Simulations of human exposure yielded concentration estimates comparable to those generated using the previously published model, with concentrations in offspring differing by less than 12%. HEDs calculated using our PK model were about 2 orders of magnitude lower than those generated using allometric scaling. Our PK model can be used to calculate internal dose metrics for offspring and corresponding HEDs and thus informs assessment of developmental toxicity risks associated with LPECs. (Published by Oxford University Press on behalf of the Society of Toxicology 2022.)
Databáze:	MEDLINE
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