Document Detail

Development of PBPK models for PFOA and PFOS for human pregnancy and lactation life stages.
MedLine Citation:
PMID:  23151209     Owner:  NLM     Status:  MEDLINE    
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.
Anne E Loccisano; Matthew P Longnecker; Jerry L Campbell; Melvin E Andersen; Harvey J Clewell
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Intramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of toxicology and environmental health. Part A     Volume:  76     ISSN:  1528-7394     ISO Abbreviation:  J. Toxicol. Environ. Health Part A     Publication Date:  2013  
Date Detail:
Created Date:  2012-11-15     Completed Date:  2013-01-17     Revised Date:  2014-01-10    
Medline Journal Info:
Nlm Unique ID:  100960995     Medline TA:  J Toxicol Environ Health A     Country:  England    
Other Details:
Languages:  eng     Pagination:  25-57     Citation Subset:  IM    
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MeSH Terms
Alkanesulfonic Acids / pharmacokinetics*
Caprylates / pharmacokinetics*
Computer Simulation
Fluorocarbons / pharmacokinetics*
Infant, Newborn
Kidney / metabolism
Lactation / metabolism*
Maternal Exposure
Maternal-Fetal Exchange
Models, Biological*
Pregnancy / metabolism*
Protein Binding
Risk Factors
Grant Support
Reg. No./Substance:
0/Alkanesulfonic Acids; 0/Caprylates; 0/Fluorocarbons; 1763-23-1/perfluorooctane sulfonic acid; 335-67-1/perfluorooctanoic acid

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