FDA/CFSAN/OFAS/DFCN, 5001 Campus Drive, HFS 275, College Park, MD 20740, United States.
FDA/NCTR, 3900 NCTR Road, Jefferson, AR 72079, United States.
Food Chem Toxicol. 2018 Feb;112:375-382. doi: 10.1016/j.fct.2018.01.012. Epub 2018 Jan 11.
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.
多氟化合物（PFCs）被授权作为食品接触用纸的防油剂使用。由于 C8-PFCs（8 个碳原子）已知会在组织中积累，因此在许多食品接触应用中，较短链的 C6-PFCs（6 个碳原子）已经取代了 C8-PFCs。然而，C6-PFCs 对人体生物持久性的潜在影响尚未得到充分评估。我们首次提供了关键代谢物 6:2 氟调聚醇（6:2 FTOH）的内部暴露估计值，6:2 FTOH 是 C6-PFCs 的单体成分，这扩展了我们对暴露的理解，超出了对外暴露估计值的理解。我们使用发表的大鼠和人体研究中关于 6:2 FTOH 的药代动力学数据，估算了其代谢物的清除率和曲线下面积（AUC）：5:3 氟调聚醇羧酸（5:3 A）、全氟己酸（PFHxA）和全氟庚酸（PFHpA）。在评估的代谢物中，5:3 A 在所有物种中的内部暴露量最高，且其清除率最慢。此外，5:3 A 的清除率随 6:2 FTOH 暴露量的增加而降低。我们的分析提供了深入了解与 6:2 FTOH 高生物持久性相关的 5:3 A 内部暴露增加的关联。我们的结果确定 5:3 A 是用于生物监测研究的内部 6:2 FTOH 暴露的重要生物标志物，并且对于评估慢性饮食 6:2 FTOH 暴露的毒性可能有用。
