Department of Chemistry, University of Toronto, Ontario, Canada.
Environ Health Perspect. 2011 Mar;119(3):344-50. doi: 10.1289/ehp.1002409. Epub 2010 Nov 8.
Perfluorinated carboxylic acids (PFCAs) are ubiquitous in human sera worldwide. Biotransformation of the polyfluoroalkyl phosphate esters (PAPs) is a possible source of PFCA exposure, because PAPs are used in food-contact paper packaging and have been observed in human sera.
We determined pharmacokinetic parameters for the PAP monoesters (monoPAPs) and PAP diesters (diPAPs), as well as biotransformation yields to the PFCAs, using a rat model.
The animals were dosed intravenously or by oral gavage with a mixture of 4:2, 6:2, 8:2, and 10:2 monoPAP or diPAP chain lengths. Concentrations of the PAPs and PFCAs, as well as metabolic intermediates and phase II metabolites, were monitored over time in blood, urine, and feces.
The diPAPs were bioavailable, with bioavailability decreasing as the chain length increased from 4 to 10 perfluorinated carbons. The monoPAPs were not absorbed from the gut; however, we found evidence to suggest phosphate-ester cleavage within the gut contents. We observed biotransformation to the PFCAs for both monoPAP and diPAP congeners.
Using experimentally derived biotransformation yields, perfluorooctanoic acid (PFOA) sera concentrations were predicted from the biotransformation of 8:2 diPAP at concentrations observed in human serum. Because of the long human serum half-life of PFOA, biotransformation of diPAP even with low-level exposure could over time result in significant exposure to PFOA. Although humans are exposed directly to PFCAs in food and dust, the pharmacokinetic parameters determined here suggest that PAP exposure should be considered a significant indirect source of human PFCA contamination.
全氟羧酸（PFCAs）在全球范围内的人类血清中普遍存在。多氟烷基磷酸酯（PAPs）的生物转化可能是 PFCAs 暴露的来源之一，因为 PAPs 用于食品接触纸包装，并在人类血清中观察到。
我们使用大鼠模型确定了 PAP 单酯（monoPAPs）和 PAP 二酯（diPAPs）的药代动力学参数，以及转化为 PFCAs 的生物转化产率。
动物通过静脉内或口服灌胃给予 4:2、6:2、8:2 和 10:2 单酯或二酯链长的混合物。在血液、尿液和粪便中随时间监测 PAPs 和 PFCAs 的浓度，以及代谢中间产物和相 II 代谢物。
二酯 PAP 是生物可利用的，随着链长从 4 到 10 个全氟碳原子增加，生物利用度降低。单酯 PAP 不会从肠道吸收；然而，我们发现有证据表明在肠道内容物中存在磷酸酯的裂解。我们观察到 monoPAP 和 diPAP 同系物向 PFCAs 的生物转化。
使用实验衍生的生物转化产率，从人类血清中观察到的 8:2 二酯 PAP 的生物转化预测了全氟辛酸（PFOA）血清浓度。由于 PFOA 的人类血清半衰期较长，即使低水平暴露于二酯 PAP 也可能随着时间的推移导致对 PFOA 的显著暴露。虽然人类直接暴露于食物和灰尘中的 PFCAs，但这里确定的药代动力学参数表明 PAP 暴露应被视为人类 PFCAs 污染的一个重要间接来源。
