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Development of Pbpk Models for Pfoa and Pfos for Human Pregnancy and Lactation Life Stages
Open accessAbstract
Perfluoroalkyl acid carboxylates and sulfonates (PFAA) have many consumer and industrial applications. Developmental toxicity studies in animals have raised concern about potential reproductive/developmental effects of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS); however, in humans conflicting results have been reported for associations between maternal PFAA levels and these outcomes. Risk assessments and interpretation of available human data during gestation and lactation are hindered due to lack of a framework for understanding and estimating maternal, fetal, and neonatal pharmacokinetics (PK). Physiologically based pharmacokinetic (PBPK) models were developed for PFOA and PFOS for the gestation and lactation life stages in humans to understand how the physiological changes associated with development affect pharmacokinetics of these compounds in the mother, fetus, and infant. These models were derived from PBPK models for PFOA/PFOS that were previously developed for adult humans and rats during gestation and lactation and from existing human pregnancy and lactation models developed for other chemicals. The models simulated PFOA and PFOS concentrations in fetal, infant, and maternal plasma and milk, were compared to available data in humans, and also were used to estimate maternal exposure. The models reported here identified several research needs, which include (1) the identification of transporters involved in renal resorption to explain the multiyear half-lives of these compounds in humans, (2) factors affecting clearance of PFOA/PFOS during gestation and lactation, and (3) data to estimate clearance of PFOA/PFOS in infants. These models may help address concerns regarding possible adverse health effects due to PFOA/PFOS exposure in the fetus and infant and may be useful in comparing pharmacokinetics across life stages.
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“The model considered the fetus as one compartment, and concluded that more studies are needed to better model the various factors affecting chem icals during pregnancy, such as possible changes in renal reabsorption of PFAS.”
From Pregnancy-related maternal physiological adaptations and fetal chemical exposure (2023) · cites this paper as Loccisano et al., 2013
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“The model considered the fetus as one compartment, and concluded that more studies are needed to better model the various factors affecting chem icals during pregnancy, such as possible changes in renal reabsorption of PFAS.”
From Pregnancy-related maternal physiological adaptations and fetal chemical exposure (2023) · cites this paper as Loccisano et al., 2013
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“For example, Loccisano et al. developed a human p-PBTK model for PFOS and PFOA based on earlier adult human models (Loccisano et al., 2013).”
From Pregnancy-related maternal physiological adaptations and fetal chemical exposure (2023) · cites this paper as Loccisano et al., 2013
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Metadata
- Authors
- Loccisano, A. E., Longnecker, M. P., Campbell, J. L., Andersen, M. E., & Clewell, H. J.
- Affiliations
- The Hamner Institutes for Health Sciences (US)
- National Institutes of Health (US)
- Center for Human Health Assessment, The Hamner Institutes for Health Sciences , Research Triangle Park, North Carolina, USA
- Corresponding author
- Loccisano, Anne E.
- Venue
- Journal of Toxicology and Environmental Health, Part A
- Publisher
- Informa UK Limited
- Published
- 2012-11-14
- Volume
- 76
- Issue
- 1
- Pages
- 25-57
- ISSN
- 0098-4108 (ISSN-L)
- 1528-7394
- 1087-2620
- PMC
- PMC3502013
- OpenAlex
- W2049985148
- Cited by
- 141
- References
- 109
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 8 · 2023: 17 · 2022: 4 · 2021: 12 · 2020: 13 · 2019: 13 · 2018: 12 · 2017: 11 · 2016: 5 · 2015: 14 · 2014: 11 · 2013: 5
- FWCI
- 7.68
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Toxicology and Environmental Health (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of Environmental Health Sciences (ZIAES044008)
- Topics
- Physical Sciences › Environmental Science › Environmental Chemistry › Per- and polyfluoroalkyl substances research
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Toxic Organic Pollutants Impact
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
- Keywords
- perfluorooctanoic acid, PFOS, perfluoroalkyl acids, physiologically based pharmacokinetic modeling, human pregnancy, lactation, fetal pharmacokinetics, maternal exposure, milk concentration, clearance, developmental toxicity
- MeSH terms
- Adult, Animals, Haplorhini, Caprylates, Computer Simulation, Female, Fluorocarbons, Humans, Infant, Newborn, Kidney, Lactation, Maternal-Fetal Exchange, Models, Biological, Pregnancy, Protein Binding, Risk Factors, Alkanesulfonic Acids, Maternal Exposure, Rats
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