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DOI | 10.1093/toxsci/kft204 |
Dosimetric Anchoring of In Vivo and In Vitro Studies for Perfluorooctanoate and Perfluorooctanesulfonate | |
Wambaugh, John F.1; Setzer, R. Woodrow1; Pitruzzello, Ann M.2; Liu, Jie1; Reif, David M.1; Kleinstreuer, Nicole C.1; Wang, Nina Ching Y.3; Sipes, Nisha1; Martin, Matthew1; Das, Kaberi4; DeWitt, Jamie C.5; Strynar, Mark6; Judson, Richard1; Houck, Keith A.1; Lau, Christopher4 | |
发表日期 | 2013-12-01 |
ISSN | 1096-6080 |
卷号 | 136期号:2页码:308-327 |
英文摘要 | In order to compare between in vivo toxicity studies, dosimetry is needed to translate study-specific dose regimens into dose metrics such as tissue concentration. These tissue concentrations may then be compared with in vitro bioactivity assays to perhaps identify mechanisms relevant to the lowest observed effect level (LOEL) dose group and the onset of the observed in vivo toxicity. Here, we examine the perfluorinated compounds (PFCs) perfluorooctanoate (PFOA) and perfluorooctanesulfonate (PFOS). We analyzed 9 in vivo toxicity studies for PFOA and 13 in vivo toxicity studies for PFOS. Both PFCs caused multiple effects in various test species, strains, and genders. We used a Bayesian pharmacokinetic (PK) modeling framework to incorporate data from 6 PFOA PK studies and 2 PFOS PK studies (conducted in 3 species) to predict dose metrics for the in vivo LOELs and no observed effect levels (NOELs). We estimated PK parameters for 11 combinations of chemical, species, strain, and gender. Despite divergent study designs and species-specific PK, for a given effect, we found that the predicted dose metrics corresponding to the LOELs (and NOELs where available) occur at similar concentrations. In vitro assay results for PFOA and PFOS from EPAs ToxCast project were then examined. We found that most in vitro bioactivity occurs at concentrations lower than the predicted concentrations for the in vivo LOELs and higher than the predicted concentrations for the in vivo NOELs (where available), for a variety of nonimmunological effects. These results indicate that given sufficient PK data, the in vivo LOELs dose regimens, but not necessarily the effects, could have been predicted from in vitro studies for these 2 PFCs. |
英文关键词 | perfluorooctanoate;perfluorooctanoic acid;perfluorooctanesulfonate;perfluorooctanesulfonic acid;compartment model;saturable resorption model;pharmacokinetics;statistical analysis;Bayesian analysis;ToxCast;in vitro-in vivo extrapolation |
语种 | 英语 |
WOS记录号 | WOS:000328695500005 |
来源期刊 | TOXICOLOGICAL SCIENCES
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来源机构 | 美国环保署 |
文献类型 | 期刊论文 |
条目标识符 | http://gcip.llas.ac.cn/handle/2XKMVOVA/59740 |
作者单位 | 1.US EPA, Natl Ctr Computat Toxicol, Off Res & Dev, Res Triangle Pk, NC 27711 USA; 2.Res Triangle Inst, Res Triangle Pk, NC 27711 USA; 3.US EPA, Natl Ctr Environm Assessment, Off Res & Dev, Cincinnati, OH 45268 USA; 4.US EPA, Natl Hlth & Environm Effects Res Lab, Off Res & Dev, Res Triangle Pk, NC 27711 USA; 5.E Carolina Univ, Brody Sch Med, Dept Pharmacol & Toxicol, Greenville, NC 27834 USA; 6.US EPA, Natl Exposure Res Lab, Off Res & Dev, Res Triangle Pk, NC 27711 USA |
推荐引用方式 GB/T 7714 | Wambaugh, John F.,Setzer, R. Woodrow,Pitruzzello, Ann M.,et al. Dosimetric Anchoring of In Vivo and In Vitro Studies for Perfluorooctanoate and Perfluorooctanesulfonate[J]. 美国环保署,2013,136(2):308-327. |
APA | Wambaugh, John F..,Setzer, R. Woodrow.,Pitruzzello, Ann M..,Liu, Jie.,Reif, David M..,...&Lau, Christopher.(2013).Dosimetric Anchoring of In Vivo and In Vitro Studies for Perfluorooctanoate and Perfluorooctanesulfonate.TOXICOLOGICAL SCIENCES,136(2),308-327. |
MLA | Wambaugh, John F.,et al."Dosimetric Anchoring of In Vivo and In Vitro Studies for Perfluorooctanoate and Perfluorooctanesulfonate".TOXICOLOGICAL SCIENCES 136.2(2013):308-327. |
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