全氟辛烷磺酸和全氟辛酸毒理学研究进展

全氟有机化合物,尤其是其代表性化合物全氟辛烷磺酸(PFOS)和全氟辛酸(PFOA)以及它们的盐类作为持久性有机环境污染物新成员,其所造成的全球性生态系统污染已成事实。本文以近年来国内外学者对PFOS和PFOA毒理学研究资料为依据,系统地阐述了PFOS和PFOA在实验动物和人体内的吸收、分布、排泄、代谢和毒物代谢动力学,以及它们对实验动物及人类可能造成的一般毒性、肝脏毒性、神经毒性、心血管毒性、胚胎发育与生殖毒性、遗传毒性与致癌性、免疫毒性等。同时指出,由于种属差异以及一些研究资料的尚不确定性,根据现有资料对PFOA和PFOS进行安全性评价的科学性值得商榷,进一步深入对PFOA和PFOS毒作用敏感指标及毒作用机制的探讨与研究,将成为今后环境科学和预防医学领域的研究重点。     

全氟辛酸和全氟辛烷磺酸的致癌性证据及机制研究进展

全氟辛酸(perfluorooctanoic acid, PFOA)和全氟辛烷磺酸(perfluorooctane sulfonate, PFOS)是使用范围最广的全氟化合物,PFOA和PFOS具有生物蓄积性,半减期较长,生物监测提示其在人类血液中普遍存在,可能与多种潜在不良健康效应有关。本文综述了PFOA和PFOS致癌性相关的研究进展,结果表明二者与人类前列腺癌、膀胱癌和乳腺癌等癌症发生发展的因果关系尚不明确,其可能的致癌作用机制涉及氧化应激、过氧化物酶体增殖物激活受体激活、表观遗传改变等。     

持久性环境污染物全氟辛烷磺酸和全氟辛酸的污染现状研究进展

全氟辛烷磺酸（PFOS）和全氟辛酸（PFOA）是全氟有机化合物（PFCs）家族中两种代表性物质,化学性质稳定,因此被广泛应用于各领域。由于PFOS和PFOA不易挥发,很难被生物系统降解,故在世界范围内广泛存在。研究表明,PFOS和PFOA广泛存在于各类环境介质和生物体内。本文将对近年来PFOS和PFOA在环境和生物体内污染现状的相关研究资料进行综述,为进一步研究提供一些思路。     

《生活饮用水卫生标准(GB5749-2022)》中全氟辛酸与全氟辛烷磺酸标准限值的制定研究

全氟化合物尤其是全氟辛酸(PFOA)与全氟辛烷磺酸(PFOS)在我国水环境中广泛检出。考虑到饮用水暴露途径的潜在健康风险, 我国新颁布的《生活饮用水卫生标准》(GB 5749-2022)中的水质参考指标增加了PFOA和PFOS指标, 限值分别为40和80 ng/L。本研究对确定该卫生标准限值的相关技术内容进行了分析和讨论, 包括PFOA与PFOS的环境存在水平和暴露状况、健康效应、安全基准值的推导和卫生标准限值的确定等, 并提出了未来饮用水标准制定方向的展望。     

全氟辛烷磺酸和全氟辛酸的人群暴露水平和毒性研究进展

以全氟辛烷磺酸(perfluorooctane sulfonate,PFOS)和全氟辛酸(perfluorooctanoic acid,PFOA)为代表的全氟化合物(perfluorinated compounds,PFCs)广泛应用于工业生产和生活消费等各个领域。但随之而来的环境污染、人群暴露和健康危害也备受关注。目前关于全氟化合物的人群暴露以及健康效应研究已成为研究热点,该文综述了全氟化合物人群暴露状况研究以及毒性效应研究,分析了全氟化合物在血液、母乳等人体基质中的暴露水平及其对肝脏、免疫系统、内分泌系统、生殖系统和婴幼儿发育的毒性效应,并提出全氟化合物对婴幼儿及儿童的生长、发育可能存在重要影响,应将婴幼儿及儿童的PFCs暴露与健康的关系作为未来的研究重点。     

沈阳地区成人血清和脐带血中全氟有机物污染现状

目的　了解沈阳地区一般人群血清和脐带血中全氟辛烷磺酸 (PFOS)和全氟辛酸 (Perfluorooctanoicacid,PFOA)污染现状。方法　采用液相色谱 质谱仪联机选择性监测离子法 (PFOS :m z =4 99,PFOA :m z =4 1 3) ,测定脐带血和被调查者血清中PFOS和PFOA浓度。结果　男女血清中PFOS和PFOA浓度几何均数分别为 4 0 73μg L和 4 5 4 6 μg L、1 1 5 3μg L和 8 97μg L- 1 。脐带血中PFOS和PFOA浓度几何均数分别为2 2 1 4 μg L和 0 2 6 4 μg L。成人血清和脐带血中PFOS和PFOA浓度与年龄无关相关性 (p <0 0 5 )。 结论　一般人群体内也存在PFOS污染物 ,而且血清PFOS浓度高于美国人和日本人水平。人类脐带血中也存在PFOS和PFOA污染     

沈阳和重庆人群血清中全氟辛烷磺酸和全氟辛酸的污染水平比较研究

目的阐明沈阳和重庆两地一般人群血清中全氟辛烷磺酸(PFOS)和全氟辛酸(PFOA)污染水平,比较两地人群血清中PFOS和PFOA分布特征。方法采集沈阳和重庆地区无职业性PFOS和PFOA暴露人群血清,采用高压液相色谱-质谱仪联机系统测定血清中PFOS和PFOA含量。结果沈阳地区一般人群血清中PFOS和PFOA浓度中位数分别为22·40μg/L和4·32μg/L,重庆地区分别为7·40μg/L和1·00μg/L。沈阳地区人群血清中PFOS、PFOA浓度明显高于重庆地区(P<0·01)。两地区女性人群血清中PFOS和PFOA浓度均高于男性水平,沈阳地区人群血清中PFOS浓度男、女性别间差异显著(P<0·05)。重庆地区女性人群血清中PFOS、PFOA浓度与年龄呈正相关关系(rPFOS=0·298,rPFOA=0·271),50岁以上女性人群的相关程度大于13岁以下和13~50岁年龄组。结论沈阳和重庆两地人群血清中PFOS和PFOA污染水平具有显著的地区性差异和分布特征,血清中PFOS和PFOA水平与年龄存在相关性。     

全氟丁酸毒性研究进展

全氟丁酸（perfluorobutanoic acid, PFBA）作为全氟辛酸（Perfluorooctanoic acid, PFOA）和全氟辛烷磺酸（perfluorooctane sulfonate, PFOS）的替代物，应用于工业和日用品的生产中，导致近年来在环境中广泛检出PFBA。本文对PFBA的毒理学研究进行了系统综述，目前研究结果提示PFBA肝脏毒性小于PFOA和PFOS，就安全性而言可能是PFOA和PFOS的良好替代物，但仍需更规范完整的毒性数据以评估潜在不良健康效应。     

全氟化合物量子点荧光法检测

全氟化合物(perfluorinated compounds,PFCs)是一种持久性有机污染物,其代表性物质有全氟辛酸(perfluorooctanoic acid,PFOA)和全氟辛烷磺酸基化合物(perfluorooctane sulfonate,PFOS).全球PFCs年排放量中98％存在于水体中,但是自来水处理系统对PFCs影响甚小[1],因而进一步完善PFCs的检测方法具有重要意义.目前,国内外对PFCs的检测主要为高效液相色谱质谱联用法(HPLC/MS),但由于仪器昂贵其应用受到限制.     

固相萃取富集净化-高效液相色谱串联质谱法测定饮用水中全氟化合物

目的建立固相萃取浓缩与高效液相色谱串联质谱法(HPLC-MS/MS)测定饮用水中全氟辛酸(PFOA)、全氟辛烷磺酸(PFOS)、全氟癸酸(PFDA)等全氟化合物的方法。方法样品经C18固相萃取浓缩净化,应用负离子电喷雾电离,检测方式为多级反应离子监测(MRM)模式,高效液相色谱串联质谱法(HPLC-MS/MS)进行测定。结果PFOA、PFOS、PFDA在50~1000pg/ml线性范围内,线性相关系数均>0.99。在8、20.0pg/g添加水平的回收率为65%~111%,相对标准偏差为3.6%~14.6%(n=6),定量检出限为8pg/g。结论该法适用于饮用水中PFOA、PFOS、PFDA等全氟化合物的测定,具有快速、定量准确、检测灵敏等优点。     

Polyfluoroalkyl chemicals in the U.S. population: data from the National Health and Nutrition Examination Survey (NHANES) 2003-2004 and comparisons with NHANES 1999-2000

BACKGROUND: Polyfluoroalkyl chemicals (PFCs) have been used since the 1950s in numerous commercial applications. Exposure of the general U.S. population to PFCs is widespread. Since 2002, the manufacturing practices for PFCs in the United States have changed considerably. OBJECTIVES: We aimed to assess exposure to perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), perfluorononanoic acid (PFNA), and eight other PFCs in a representative 2003-2004 sample of the general U.S. population >or= 12 years of age and to determine whether serum concentrations have changed since the 1999-2000 National Health and Nutrition Examination Survey (NHANES). METHODS: By using automated solid-phase extraction coupled to isotope dilution-high-performance liquid chromatography-tandem mass spectrometry, we analyzed 2,094 serum samples collected from NHANES 2003-2004 participants. RESULTS: We detected PFOS, PFOA, PFHxS, and PFNA in > 98% of the samples. Concentrations differed by race/ethnicity and sex. Geometric mean concentrations were significantly lower (approximately 32% for PFOS, 25% for PFOA, 10% for PFHxS) and higher (100%, PFNA) than the concentrations reported in NHANES 1999-2000 (p < 0.001). CONCLUSIONS: In the general U.S. population in 2003-2004, PFOS, PFOA, PFHxS, and PFNA serum concentrations were measurable in each demographic population group studied. Geometric mean concentrations of PFOS, PFOA, and PFHxS in 2003-2004 were lower than in 1999-2000. The apparent reductions in concentrations of PFOS, PFOA, and PFHxS most likely are related to discontinuation in 2002 of industrial production by electrochemical fluorination of PFOS and related perfluorooctanesulfonyl fluoride compounds.     

Impacts of two perfluorinated compounds (PFOS and PFOA) on human hepatoma cells: cytotoxicity but no genotoxicity?

Perfluorinated compounds (PFCs) and particularly two of them, perfluoroctanoate (PFOA) and perfluorooctanesulfonate (PFOS), have been widely produced and used since 1950. They both persist in the environment and accumulate in wildlife and humans. The toxicity of PFOS and PFOA has been studied extensively in rodents with several adverse effects mainly a hepatocarcinogenic potential. Carcinogenic effects are not highlighted in humans' studies. In this study, we investigated the cytotoxic and genotoxic effects of PFOA and PFOS using human HepG2 cells after 1 or 24h of exposure. The cytotoxic and genotoxic potential was evaluated by MTT assay, single cell gel electrophoresis (SCGE) assay and micronucleus assay respectively. We measured the intracellular generation of reactive oxygen species (ROS) using dichlorofluorescein diacetate to identify a potential mechanism of toxicity. We observed a cytotoxic effect of PFOA and PFOS after 24h of exposure starting from a concentration of 200 μM (MTT: -14.6%) and 300 μM (MTT: -51.2%) respectively. We did not observe an increase of DNA damage with the comet assay or micronucleus with the micronucleus assay after exposure to the two PFCs. After 24h of exposure, both PFOA and PFOS highlight a decrease of ROS generation (-5.9% to -23%). We did not find an effect after an hour of exposure. Our findings show that PFOA and PFOS exert a cytotoxic effect on the human cells line HepG2 but nor PFOA or PFOS could induce an increase of DNA damage (DNA strand breaks and micronucleus) or reactive oxygen species at the range concentration tested. Our results do not support that oxidative stress and DNA damage are relevant for potential adverse effects of PFOA and PFOS. These results tend to support epidemiological studies that do not show evidence of carcinogenicity.     

Polyfluoroalkyl compounds in Texas children from birth through 12 years of age

Background: For > 50 years, polyfluoroalkyl compounds (PFCs) have been used worldwide, mainly as surfactants and emulsifiers, and human exposure to some PFCs is widespread.Objectives: Our goal was to report PFC serum concentrations from a convenience sample of Dallas, Texas, children from birth to < 13 years of age, and to examine age and sex differences in PFC concentrations.Methods: We analyzed 300 serum samples collected in 2009 for eight PFCs by online solid phase extraction–high performance liquid chromatography–isotope dilution–tandem mass spectrometry.Results: Perfluorohexane sulfonic acid (PFHxS), perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), and perfluorononanoic acid (PFNA) were detected in > 92% of participants; the other PFCs measured were detected less frequently. Overall median concentrations of PFOS (4.1 ng/mL) were higher than those for PFOA (2.85 ng/mL), PFNA (1.2 ng/mL), and PFHxS (1.2 ng/mL). For PFOS, PFOA, PFNA, and PFHxS, we found no significant differences (p < 0.05) by sex, significantly increasing concentrations for all four chemicals by age, and significantly positive correlations between all four compounds.Conclusions: We found no significant differences in the serum concentrations of PFOS, PFOA, PFNA, and PFHxS by sex, but increasing concentrations with age. Our results suggest that these 300 Texas children from birth through 12 years of age continued to be exposed to several PFCs in late 2009, years after changes in production of some PFCs in the United States.     

Isomer profiles of perfluorochemicals in matched maternal, cord, and house dust samples: manufacturing sources and transplacental transfer

Background: Perfluorochemicals (PFCs) are detectable in the general population and in the human environment, including house dust. Sources are not well characterized, but isomer patterns should enable differentiation of historical and contemporary manufacturing sources. Isomer-specific maternal–fetal transfer of PFCs has not been examined despite known developmental toxicity of perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) in rodents.Objectives: We elucidated relative contributions of electrochemical (phased out in 2001) and telomer (contemporary) PFCs in dust and measured how transplacental transfer efficiency (TTE; based on a comparison of maternal and cord sera concentrations) is affected by perfluorinated chain length and isomer branching pattern.Methods: We analyzed matching samples of house dust (n = 18), maternal sera (n = 20), and umbilical cord sera (n = 20) by isomer-specific high-performance liquid chromatography tandem mass spectrometry.Results: PFOA isomer signatures revealed that telomer sources accounted for 0–95% of total PFOA in house dust (median, 31%). This may partly explain why serum PFOA concentrations are not declining in some countries despite the phase-out of electrochemical PFOA. TTE data indicate that total branched isomers crossed the placenta more efficiently than did linear isomers for both PFOS (p < 0.01) and PFOA (p = 0.02) and that placental transfer of branched isomers of PFOS increased as the branching point moved closer to the sulfonate (SO₃^–) end of the molecule.Conclusions: Results suggest that humans are exposed to telomer PFOA, but larger studies that also account for dietary sources should be conducted. The exposure profile of PFOS and PFOA isomers can differ between the mother and fetus—an important consideration for perinatal epidemiology studies of PFCs.     

Pilot study on the perfluorooctanesulfonate and perfluorooctanoate exposure of the German general population

Perfluorinated chemicals (PFCs) are used in a wide variety of consumer products. Major fields of application include surfactants, surface protection (e.g., for textiles, carpets, and upholstery), paper treatment (e.g., for food packages), and lubricants. Perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) are raw materials or manufacturing aids for some PFCs and can be released of those by biotic and/or metabolic decomposition. Due to their widespread use, persistence and bioaccumulative properties they are taken up by the general population from different sources. This might be a problem for environmental medicine because in animal studies PFOS and PFOA provoked various types of cancer and showed developmental toxic potential besides other adverse health effects.

We determined the PFOS and PFOA plasma concentrations of 105 non-smokers out of the German general population as a first estimate of the exposure situation in Germany. We employed an analytical method based on serum protein precipitation followed by HPLC with MS/MS-detection. The median plasma concentrations of all participants were 22.3 and 6.8 μg/l, the 95th percentiles 54.3 and 14.6 μg/l for PFOS and PFOA, respectively. These values are comparable with those of other biomonitoring studies. In our study, men were higher burdened both with PFOS (median: 27.1 vs. 19.9 μg/l) and PFOA (median: 8.3 vs. 5.8 μg/l) than women. No significant influence of age on PFOS and PFOA plasma concentrations could be observed. A strong correlation (r=0.82) between PFOS and PFOA plasma levels indicates the same exposure sources. The ubiquitous internal exposure of the general population to PFOS and PFOA must lead to further activities primarily regarding clarification of sources, metabolism, pharmacokinetics, and health effects.     

Excretion of PFOA and PFOS in Male Rats During a Subchronic Exposure

Perfluorinated compounds (PFCs), a class of synthetic surfactants that are widely used, have become global environmental contaminants because of their high persistence and bioaccumulation. An increasing number of studies have described the pharmacokinetics of PFCs following in vivo exposure, however, few papers have focused on the excretion of these compounds during a period of consecutive exposure. In this study, the excretions of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) in male Sprague–Dawley rats gavaged consecutively for 28 days were investigated and compared. The faster elimination rate in urine compared to feces indicated that urinary excretion is the primary clearance route in rats for either PFOA or PFOS. During the first 24 h after administration of PFOA (5 and 20 mg/kg body weight/day), about 24.7–29.6% of the oral dose was excreted through urine and feces, while for PFOS, the excretion amounts were only 2.6–2.8% of the total gavaged doses (5 and 20 mg/kg body weight/day). The excretion rates of both PFCs increased with increasing exposure doses. The higher elimination rate of PFOA through excretion indicated its lower accumulation in rats, thus inducing possible lower toxicities compared to PFOS.     

Levels of Perfluorinated Chemicals in Municipal Drinking Water from Catalonia,Spain: Public Health Implications

In this study, the concentrations of 13 perfluorinated compounds (PFCs) (PFBuS, PFHxS, PFOS, THPFOS, PFHxA, PFHpA, PFOA, PFNA, PFDA, PFUnDA, PFDoDA, PFTDA, and PFOSA) were analyzed in municipal drinking water samples collected at 40 different locations from 5 different zones of Catalonia, Spain. Detection limits ranged between 0.02 (PFHxS) and 0.85 ng/L (PFOA). The most frequent compounds were PFOS and PFHxS, which were detected in 35 and 31 samples, with maximum concentrations of 58.1 and 5.30 ng/L, respectively. PFBuS, PFHxA, and PFOA were also frequently detected (29, 27, and 26 samples, respectively), with maximum levels of 69.4, 8.55, and 57.4 ng/L. In contrast, PFDoDA and PFTDA could not be detected in any sample. The most contaminated water samples were found in the Barcelona Province, whereas none of the analyzed PFCs could be detected in two samples (Banyoles and Lleida), and only one PFC could be detected in four of the samples. Assuming a human water consumption of 2 L/day, the maximum daily intake of PFOS and PFOA from municipal drinking water would be, for a subject of 70 kg of body weight, 1.7 and 1.6 ng/kg/day. This is clearly lower than the respective Tolerable Daily Intake set by the European Food Safety Authority. In all samples, PFOS and PFOA also showed lower levels than the short-term provisional health advisory limit for drinking water (200 ng PFOS/L and 400 ng PFOA/L) set by the US Environmental Protection Agency. Although PFOS and PFOA concentrations found in drinking water in Catalonia are not expected to pose human health risks, safety limits for exposure to the remaining PFCs are clearly necessary, as health-based drinking water concentration protective for lifetime exposure is set to 40 ng/L for PFOA.     

Occurrence of perfluorinated substances in an adult German population in southern Bavaria

Objectives Perfluorinated compounds (PFCs) are a large group of chemicals produced for several decades and widely used for many industrial and consumer applications. Because of their global occurrence in different environmental media, their persistence, and their potential to bioaccumulate in organisms they are of toxicological and public concern. Methods In the present study, the internal exposure to perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) in 356 human plasma samples collected from an adult population in Germany in 2005 is quantified. Results We were able to detect the target analytes in all plasma samples and observed a significant correlation between the PFOS and PFOA concentrations. In female participants, the levels of PFOS and PFOA ranged between 2.5–30.7 (median: 10.9 μg/l) and 1.5–16.2 μg/l (median: 4.8 μg/l), respectively. In males we observed concentrations from 2.1 to 55.0 μg/l (median: 13.7 μg/l) for PFOS and from 0.5 to 19.1 μg/l (median: 5.7 μg/l) for PFOA. A significant correlation between both PFOS and PFOA concentrations and gender was observed. We also found increased levels of the PFCs with increasing age of the participants, but this association reached statistical significance among females only. Conclusions Our data agree well with results of other recent studies in Europe and suggest that the current exposure of the adult German population is lower than the exposure of the US and Canadian population. The sources of human exposure are currently not well understood. Toxicological implications are restricted to animal studies and occupational investigations not adequate for quantitative risk assessment in humans. Overall, more scientific research is necessary to characterize the body burden of PFCs (especially for relevant subsets of the population) and the main sources and routes, which are responsible for human exposure and possible health implications of these compounds.     

The influence of time, sex and geographic factors on levels of perfluorooctane sulfonate and perfluorooctanoate in human serum over the last 25 years

Perfluorooctanesulfonate (PFOS) and perfluorooctanoate (PFOA) are important perfluorochemicals (PFCs) in various applications. Recently, it has been shown that these chemicals are widespread in the environment, wildlife and humans. But the kinds of factors that affect their levels in serum are unclear, and it is also not clear whether exposure to them is increasing or not. To investigate the impacts of time, geographical location and sex on the levels of these chemicals, we measured PFOS and PFOA concentrations in human sera samples collected both historically and recently in Miyagi, Akita and Kyoto Prefectures in Japan. The PFOS and PFOA levels in sera [Geometric Mean (Geometric Standard Deviation)] (microg/L) in 2003 ranged from 3.5 (2.9) in Miyagi to 28.1 (1.5) in Kyoto for PFOS and from 2.8 (1.5) to 12.4 (1.4) for PFOA. Historical samples collected from females demonstrated that PFOS and PFOA concentrations have increased by factors of 3 and 14, respectively, over the past 25 yr. There are large sex differences in PFOS and PFOA concentrations in serum at all locations. Furthermore, there are predominant regional differences for both PFOS and PFOA concentrations. In Kyoto the concentrations of PFOA in dwellers who had lived in the Kinki area for more than 2 yr were significantly higher than in people who had recently moved into the area, in both sexes. This finding suggests that there are sources of PFOA in the Kinki area that have raised the PFOA serum levels of its inhabitants. Further studies are needed to elucidate these sources in the Kinki area of Japan.