Benskin Jonathan P, De Silva Amila O, Martin Leah J, Arsenault Gilles, McCrindle Robert, Riddell Nicole, Mabury Scott A, Martin Jonathan W
Division of Analytical and Environmental Toxicology, Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alverta, Canada.
Environ Toxicol Chem. 2009 Mar;28(3):542-54. doi: 10.1897/08-239.1. Epub 2008 Oct 21.
Perfluorinated acids (PFAs) and their precursors (PFA-precursors) exist in the environment as linear and multiple branched isomers. These isomers are hypothesized to have different biological properties, but no isomer-specific data are currently available. The present study is the first in a two-part project examining PFA isomer-specific uptake, tissue distribution, and elimination in a rodent model. Seven male Sprague-Dawley rats were administered a single gavage dose of approximately 500 microg/kg body weight perfluorooctane sulfonate (C(8)F(17)SO(3)(-), PFOS), perfluorooctanoic acid (C(7)F(15)CO(2)H, PFOA), and perfluorononanoic acid (C(8)F(17)CO(2)H, PFNA) and 30 microg/kg body weight perfluorohexane sulfonate (C(6)F(13)SO(3)(-), PFHxS). Over the subsequent 38 d, urine, feces, and tail-vein blood samples were collected intermittently, while larger blood volumes and tissues were collected on days 3 and 38 for isomer analysis by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). For all PFAs, branched isomers generally had lower blood depuration half-lives than the corresponding linear isomer. The most remarkable exception was for the PFOS isomer containing an alpha-perfluoromethyl branch (1m-PFOS), which was threefold more persistent than linear PFOS, possibly due to steric shielding of the hydrophilic sulfonate moiety. For perfluoromonomethyl-branched isomers of PFOS, a structure-property relationship was observed whereby branching toward the sulfonate end of the perfluoroalkyl chain resulted in increased half-lives. For PFHxS, PFOA, and PFOS, preferential elimination of branched isomers occurred primarily via urine, whereas for PFNA preferential elimination of the isopropyl isomer occurred via both urine and feces. Changes in the blood isomer profiles over time and their inverse correlation to isomer elimination patterns in urine, feces, or both provided unequivocal evidence of significant isomer-specific biological handling. Source assignment based on PFA isomer profiles in biota must therefore be conducted with caution, because isomer profiles are unlikely to be conserved in biological samples.
全氟辛酸（PFAs）及其前体（PFA - 前体）以直链和多支链异构体的形式存在于环境中。据推测，这些异构体具有不同的生物学特性，但目前尚无异构体特异性数据。本研究是一个分为两部分的项目中的首个部分，该项目旨在研究啮齿动物模型中PFA异构体特异性的摄取、组织分布和消除情况。给7只雄性斯普拉格 - 道利大鼠经口单次灌胃给予约500微克/千克体重的全氟辛烷磺酸（C₈F₁₇SO₃⁻，PFOS）、全氟辛酸（C₇F₁₅CO₂H，PFOA）和全氟壬酸（C₈F₁₇CO₂H，PFNA），以及30微克/千克体重的全氟己烷磺酸（C₆F₁₃SO₃⁻，PFHxS）。在随后的38天里，间歇性收集尿液、粪便和尾静脉血样，而在第3天和第38天收集较多血量和组织，通过高效液相色谱 - 串联质谱法（HPLC - MS/MS）进行异构体分析。对于所有的PFAs，支链异构体的血液净化半衰期通常比相应的直链异构体短。最显著的例外是含有α - 全氟甲基支链的PFOS异构体（1m - PFOS），其持久性是直链PFOS的三倍，这可能是由于亲水性磺酸基团的空间屏蔽作用。对于PFOS的全氟单甲基支链异构体，观察到一种结构 - 性质关系，即朝着全氟烷基链的磺酸端分支会导致半衰期增加。对于PFHxS、PFOA和PFOS，支链异构体的优先消除主要通过尿液进行，而对于PFNA，异丙基异构体的优先消除则通过尿液和粪便两者进行。血液中异构体谱随时间的变化及其与尿液、粪便或两者中异构体消除模式的负相关，为显著的异构体特异性生物处理提供了明确证据。因此，基于生物群中PFA异构体谱进行源分配时必须谨慎，因为异构体谱在生物样品中不太可能保持不变。
