The Exposure and Renal Excretion of Perfluoroalkyl Substances and Their Pepresentative Isomers in Humans
|Keywords||perfluoroalkyl substances isomer human exposure renalexcretion serum/whole blood distribution ratio|
After decades of production and applications, perfluoroalkyl substances (PFASs) are ubiquitous present in the environment and have been widely detected in human samples. The most commonly detected PFASs in human samples are perfluorooctanesulfonate (PFOS) and perfluorooctanoate (PFOA). PFASs are persistent and bioaccumulative and display adverse effects to human health. Historically, two major manufacturing methods, namely telomerization and electrochemical fluorination (ECF), have been used to produce PFASs and their precursors. ECF was used to produce PFOA beginning in1947and PFOS and its precursors in1949. This process was known to yield a complex, yet rather consistent, mixture of linear (ca.70%for PFOS,80%for PFOA) and branched isomers (ca.30%for PFOS,20%for PFOA) in final products. However, the telomerization method, which was developed by Dupont in the1970s, produces typically pure linear isomer. The isomers of PFOS and PFOA display different environmental behaviors, pharmacokinetics and toxicity. Thus, it is of great importance to study the distribution and elimination effciency of isomers for human exposure source analysis and health risk assessment.In the present thesis, a new isomer-specific PFAS analytial method was developed for the first time to analyze229serum samples collected in three typical cities (Shijiazhuang, Handan and Tianjin) in North China. The objectives were to quantify PFASs and the isomer profiles of PFOS and PFOA in general Chinese people, to elucidate the impacts of gender and age on the isomer-specific accumulation pattern, and to try to evaluate the sources of PFOS and PFOA exposure in these populations. Subsequently, to estimate the renal excretion of PFASs and isomers of PFOS and PFOA, paired blood and urine samples (n=86) from adults in Shijiazhuang and Handan were analyzed, and rates of renal clearance and half-lives were estimated. At last, to study the ditribution of PFASs and the isomers of PFOS and PFOA in whole blood and serum, sixty paired samples from thirty couples in Shijiazhuang were analyzed. Among the129serum samples from Shijiazhuang and Handan, total PFOS (∑PFOS, mean33.3ng/mL) was the predominant PFAS followed by perfluorohexanesulfonate (PFHxS,2.95ng/mL), total PFOA (∑PFOA,2.38ng/mL), and perfluorononanoate (PFNA,0.51ng/mL). The level of∑PFOS appeared to be higher than in people from North America in recent years. The mean concentrations of∑PFASs in the participants living in urban Shijiazhuang (59.0ng/mL) and urban Handan (35.6ng/mL) were significantly higher (p<0.001and p=0.041, respectively) than those living in the rural district of Shijiazhuang (24.3ng/mL). The young female sub-population had the lowest∑PFAS concentrations compared with males and older females. The mean concentration of perfluoroalkane sulfonates (PFSAs) in people (n=129) from Shijiazhuang and Handan was higher than in people (n=100) from Tianjin, while, people in Tianjin displayed higher level of perfluoroalkyl carboxylates (PFCAs) than in Shijiazhuang and Handan. These suggest that the people in different regions may have different exposure sources of PFASs.The proportion of linear PFOS (n-PFOS) inFOS was only48.1%for people in Shijiazhuang and Handan, which is lower than people in Tianjin (59.2%). They are both much lower than what was present in technical PFOS from the major historical manufacturer (ca.70%linear). Moreover, the proportion of n-PFOS decreased significantly with increasing∑PFOS concentration in the229serum samples. The results may have two implications:i) high content of branched PFOS isomers in serum is a biomarker of exposure to PFOS-precursors (PreFOS), and ii) that people with the highest∑PFOS concentrations are exposed disproportionately to high concentrations of PreFOS. On average, linear PFOA (n-PFOA) contributed96.1%of∑PFOA in serum samples from Shijiazhuang and Handan, significantly higher than in technical PFOA (ca.75-80%linear), but lower than in Americans (close to100%) in2007-2008, suggesting ECF PFOA was still be used in China.A newly sensitive isomer-specific method was developed to analyze PFASs in human urine, which permitted the detection of many PFASs in human urine for the first time. The levels of most PFASs in urine correlated positively with their levels in paired blood (p<0.05). Thus, urine could be used to monitor PFASs exposure in humans. In general, shorter PFCAs were excreted more efficiently than longer ones, and PFCAs were excreted more efficiently than PFSAs of the same carbon chain-length. However, PFOS (a C8compound) was excreted more efficiently than PFHxS (a C6compound). Among PFOS and PFOA isomers, major branched isomers were more efficiently excreted than the corresponding linear isomer except1m-PFOS. The proportion of linear perfluorooctane sulfonamide (PFOSA) was significantly higher (p<0.001) in urine (median84%) than in blood (65%), demonstrating that linear PFOSA is preferentially excreted via urine relative to branched isomers; opposite to the findings for renal excretion of PFOS and PFOA isomers. A one-compartment model was used to estimate the biological elimination half-lives of PFASs. Among all PFASs, the estimated arithmetic mean with standard error elimination half-lives ranged from0.5±0.1years (5m-PFOA) to90±11years (1m-PFOS). Renal excretion was the major elimination route for PFOA, but for PFOS and PFHxS (and possibly other long-chain PFCAs) menstruation and other routes of excretion likely contribute to overall elimination.For most PFASs, the levels in the whole blood correlated positively with the levels in paired serum samples (n=60, r=0.49-0.87,p<0.001) except PFHxA and PFNA. PFHxA in serum samples was significantly lower (p<0.001) than in the paired whole blood samples, while, for PFOA (p=0.105) and PFNA (p=0.237), no significantly differences were found, but for the longer chain-length PFCAs, perfluorodecanoate (PFDA) and perfluoroundecanoate (PFUdA) in serum samples was significantly higher (p<0.001) than in the paired whole blood samples. These suggested that shorter chain-length PFCAs preferrd to distribute in the blood corpuscles. Unlike PFHxA (C6) and PFOA (C8), althrough kept the same chain-length, PFHxS (C6) and PFOS (C8) in serum samples were significantly higher (p<0.001) than in the paired whole blood samples, which implied functional groups (carboxyl group and sulfonic group) also played an important role in the ditribution of serum and whole blood.The median serum/whole blood distribution ratios were showed as follows, PFHxS (1.67), PFOS (1.68), PFHxA (0.34), PFOA (1.24), PFNA (0.85), PFDA (1.39) and PFUdA (1.60). For PFOS isomers, the median serum/whole blood distribution ratios for all the monomethyl branched PFOS were close to or greater than2(1.94～2.69) except iso-PFOS, while, the median ratios for n-PFOS, iso-PFOS and2-PFOS were similar and lower than2(1.40～1.54). For PFOA isomers, the median ratios for branched PFOA were lower than1, and was1.29for n-PFOA. These suggested the isomers distribution in serum and whole blood were different. When transfer PFASs concentration from whole blood samples to serum samples, using the factor2would lead to overestimation for most PFASs except some branched PFOS isomers. Using haematocrit calculated ratios (1.69for female and1.85for male) to transfer, would be suitable for PFSAs (PFHxS and PFOS) and long chain-length PFCA (PFUdA), but also overestimation for other PFASs.