A physiologically based pharmacokinetic model for developmental exposure to BDE-47 in rats.
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.
Emond
Claude
C
Département de santé environnementale et santé au travail Faculté de médecine, Université de Montréal, P.O. Box 6128, Main Station, Montréal, Québec, Canada H3C 3J7. claude.emond@umontreal.ca
Raymer
James H
JH
Studabaker
William B
WB
Garner
C Edwin
CE
Birnbaum
Linda S
LS
D000818:Animals; D004785:Environmental Pollutants / Q000493:pharmacokinetics*; D005260:Female; D005333:Fetus / Q000378:metabolism; D055768:Halogenated Diphenyl Ethers; D006801:Humans; D008297:Male; D018811:Maternal Exposure; D008431:Maternal-Fetal Exchange; D008954:Models, Biological; D011075:Polybrominated Biphenyls / Q000493:pharmacokinetics*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity; D014018:Tissue Distribution
D004785:Environmental Pollutants; D055768:Halogenated Diphenyl Ethers; D011075:Polybrominated Biphenyls; C511295:2,2',4,4'-tetrabromodiphenyl ether