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Internal exposure-based pharmacokinetic evaluation of potential for biopersistence of 6:2 fluorotelomer alcohol (FTOH) and its metabolites
Food and Chemical Toxicology ( IF 3.9 ) Pub Date : 2018-01-11 , DOI: 10.1016/j.fct.2018.01.012
Shruti V. Kabadi , Jeffrey Fisher , Jason Aungst , Penelope Rice

Polyfluorinated compounds (PFCs) are authorized for use as greaseproofing agents in food contact paper. As C8-PFCs (8-carbons) are known to accumulate in tissues, shorter-chain C6-PFCs (6-carbons) have replaced C8-PFCs in many food contact applications. However, the potential of C6-PFCs for human biopersistence has not been fully evaluated. For the first time, we provide internal exposure estimates to key metabolites of 6:2 fluorotelomer alcohol (6:2 FTOH), a monomeric component of C6-PFCs, to extend our understanding of exposure beyond estimates of external exposure. Pharmacokinetic data from published rat and human studies on 6:2 FTOH were used to estimate clearance and area under the curve (AUC) for its metabolites: 5:3 fluorotelomer carboxylic acid (5:3 A), perfluorohexanoic acid (PFHxA) and perfluoroheptanoic acid (PFHpA). Internal exposure to 5:3 A was the highest of evaluated metabolites across species and it had the slowest clearance. Additionally, 5:3 A clearance decreased with increasing 6:2 FTOH exposure. Our analysis provides insight into association of increased internal 5:3 A exposure with high biopersistence potential of 6:2 FTOH. Our results identify 5:3 A as an important biomarker of internal 6:2 FTOH exposure for use in biomonitoring studies, and are potentially useful for toxicological assessment of chronic dietary 6:2 FTOH exposure.



中文翻译:

基于内部暴露的6:2含氟端粒醇(FTOH)及其代谢物生物持久性潜力的药代动力学评估

多氟化合物(PFC)已被授权在食品接触纸中用作防油剂。由于已知C8-PFC(8碳)会在组织中积累,因此在许多食品接触应用中,短链C6-PFC(6碳)已取代了C8-PFC。但是,尚未完全评估C6-PFC对人类生物持久性的潜力。我们首次为6:2含氟端粒醇(6:2 FTOH)(C6-PFCs的单体成分)的关键代谢物提供内部暴露估算,以使我们对暴露的了解超出了对外部暴露的估算。使用来自已发表的大鼠和人体研究的6:2 FTOH的药代动力学数据来估算其代谢产物:5:3氟调聚物羧酸(5:3 A),全氟己酸(PFHxA)和全氟庚酸的清除率和曲线下面积(AUC)酸(PFHpA)。内部暴露于5:3 A是物种中评估的代谢产物最高,清除速率最慢。此外,随着6:2 FTOH暴露的增加,清除率降低了5:3。我们的分析提供了内部5:3 A暴露增加与6:2 FTOH的高生物持久性关联的见解。我们的研究结果确定5:3 A是内部6:2 FTOH暴露的重要生物标志物,可用于生物监测研究,并且可能对慢性饮食6:2 FTOH暴露的毒理学评估有用。

更新日期:2018-01-11
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