A physiologically based pharmacokinetic model for developmental exposure to BDE-47 in rats

Journal Article · Mon Feb 01 00:00:00 EST 2010 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2009.10.019· OSTI ID:21344851

Emond, Claude ^[1]; Raymer, James H; Studabaker, William B; Garner, C Edwin ^[2]; Birnbaum, Linda S ^[3]

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1. Departement de sante environnementale et sante au travail Faculte de medecine, Universite de Montreal, P.O. Box 6128, Main Station, Montreal, Quebec, H3C 3J7 (Canada)
2. RTI International, Research Triangle Park, NC 27709 (United States)
3. Office of Research and Development, National Center for Environmental Assessment, U.S. Environmental Protection Agency, Research Triangle Park, NC 27709 (United States)

Polybrominated diphenyl ethers (PBDEs) are used commercially as additive flame retardants and have been shown to transfer into environmental compartments, where they have the potential to bioaccumulate in wildlife and humans. Of the 209 possible PBDEs, 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) is usually the dominant congener found in human blood and milk samples. BDE-47 has been shown to have endocrine activity and produce developmental, reproductive, and neurotoxic effects. The objective of this study was to develop a physiologically based pharmacokinetic (PBPK) model for BDE-47 in male and female (pregnant and non-pregnant) adult rats to facilitate investigations of developmental exposure. This model consists of eight compartments: liver, brain, adipose tissue, kidney, placenta, fetus, blood, and the rest of the body. Concentrations of BDE-47 from the literature and from maternal-fetal pharmacokinetic studies conducted at RTI International were used to parameterize and evaluate the model. The results showed that the model simulated BDE-47 tissue concentrations in adult male, maternal, and fetal compartments within the standard deviations of the experimental data. The model's ability to estimate BDE-47 concentrations in the fetus after maternal exposure will be useful to design in utero exposure/effect studies. This PBPK model is the first one designed for any PBDE pharmaco/toxicokinetic description. The next steps will be to expand this model to simulate BDE-47 pharmacokinetics and distributions across species (mice), and then extrapolate it to humans. After mouse and human model development, additional PBDE congeners will be incorporated into the model and simulated as a mixture.

• OSTI ID: 21344851
• Journal Information: Toxicology and Applied Pharmacology, Vol. 242, Issue 3; Other Information: DOI: 10.1016/j.taap.2009.10.019; PII: S0041-008X(09)00464-5; Copyright (c) 2009 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ADIPOSE TISSUE
BRAIN
BROMINATED AROMATIC HYDROCARBONS
FETUSES
KIDNEYS
LIVER
MEN
PHENYL ETHER
PLACENTA
RATS
SIMULATION
TOXICITY
ANIMAL TISSUES
ANIMALS
AROMATICS
BODY
CENTRAL NERVOUS SYSTEM
CONNECTIVE TISSUE
DIGESTIVE SYSTEM
ETHERS
FETAL MEMBRANES
GLANDS
HALOGENATED AROMATIC HYDROCARBONS
MALES
MAMMALS
MAN
MEMBRANES
NERVOUS SYSTEM
ORGANIC BROMINE COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
ORGANS
PRIMATES
RODENTS
VERTEBRATES