全氟辛烷磺酸和全氟辛酸神经毒性机制研究进展

全氟化合物(Perfluorinated Compounds,PFCs)作为新型持久性有机环境污染物,其对全球生态系统的影响逐渐受到多个研究领域的重视。全氟辛烷磺酸(Perfluorooctane Sulfonate,PFOS)和全氟辛酸(Pe-fluorooctane Acid,PFOA)是目前最受关注的两种典型全氟化合物。本文对近年来PFOS和PFOA对生物体的神经毒性及其可能机制研究作一综述。     

全氟烷基磺酸和全氟烷基羧酸在水生动物体内富集及毒性研究进展

全氟烷基磺酸(perfluoroalkyl sulfonic acids,PFOS)和全氟烷基羧酸(perfluoroalkyl carboxylic acids,PFOA)均属于不易挥发性酸且具有较高的水溶性。进入水环境的PFOS、PFOA易在水生动物肝脏、肌肉和血液中蓄积,对水生动物体的毒性影响日趋加剧。结合近年来国内外毒理学研究进展,该文综述了PFOS、PFOA在水生动物体中的分布及富集规律,以及PFOS、PFOA对水生动物的毒性效应(生长发育、生殖、神经、肝脏、免疫等)和机制,并对其未来PFOS、PFOA的毒性研究方向进行了展望。     

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。     

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。     

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。     

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     

《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。     

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。     

武汉市饮用水中全氟辛烷磺酸和全氟辛酸健康风险评价

目的对武汉市饮用水全氟辛烷磺酸(PFOS)和全氟辛酸(PFOA)含量进行调查和风险评估。方法武汉市9个市政水厂,每个水厂采集水源水、出厂水、末梢水各一份,采用固相萃取-高效液相色谱串联质谱法,测定水样中的PFOS和PFOA含量,实验数据采用SPSS 11.0统计软件进行分析,运用化学污染物风险评价模型进行风险概率评价。结果所有水样均未检出PFOS。饮用水中PFOA含量水源水为18.12~119.31 ng/L,出厂水为17.25~108.98 ng/L,末梢水17.01~112.91 ng/L。PFOA含量水源水与出厂水、末梢水,出厂水与末梢水之间均存在正相关关系(P≤0.01),但水源水、出厂水、末梢水中PFOA浓度分布差异无统计学意义。以汉江和长江为水源地的饮用水中PFOA通过饮水途径对饮用者所致健康危害的个人年风险分别为3.0×10-11和1.2×10-10。结论武汉市饮用水中存在PFOA污染,PFOA通过饮水途径对饮用者所致健康危害的个人年风险低于国际辐射防护委员会(ICRP)推荐的最大可接受水平。     

Phytotoxicity of PFOS and PFOA to Brassica chinensis in different Chinese soils

PFOS and PFOA are potential persistent organic pollutants that have raised many concerns in recent years. Research focusing on phytotoxicity of PFOS and PFOA to higher plants is necessary for their risk assessments. However, few toxicity data exist for PFOS or PFOA and higher plants. Here we investigated phytotoxicity of PFOS and PFOA to Brassica chinensis root growth in six different Chinese soils varying widely in soil properties using a standardized root length assay. The effective concentrations of added PFOS and PFOA causing 50% inhibition (EC₅₀) ranged from 95 to >200 mg kg⁻¹ for PFOS and from 107 to 246 mg kg⁻¹ for PFOA, respectively, representing more than 2.1- and 2.3-fold variation among the tested soils. Regressions of soil PFOS and PFOA toxicity threshold values (EC_x and NOECs) with various soil properties showed that the amount of organic matter was the most significant factor affecting their toxicity to B. chinensis.     

Transplacental exposure of neonates to perfluorooctanesulfonate and perfluorooctanoate: a pilot study

Objectives Perfluorooctanesulfonate (PFOS) and perfluorooctanoate (PFOA) can be released of perfluorinated compounds by biotic and/or metabolic decomposition. Due to their ubiquitous occurrence, persistence and bioaccumulative properties they can be found in blood of the general population all over the world. In animal studies PFOS and PFOA provoked cancer and showed developmental toxic potential besides other adverse health effects. On the basis of the comparison of maternal and umbilical cord plasma sample pairs we wanted to examine whether infants are exposed to PFOS and PFOA via their mothers’ blood. Methods We determined PFOS and PFOA in 11 plasma samples of mothers and the 11 corresponding cord plasma samples of neonates. An analytical method based on plasma protein precipitation followed by HPLC with MS/MS-detection was employed. As internal standards we used 1,2,3,4-¹³C₄-PFOS and 1,2-¹³C₂-PFOA. Results We found PFOS and PFOA in every plasma sample analysed. In maternal plasma samples PFOS concentrations were consistently higher compared to those of the related cord plasma samples (median: 13.0 μg/l vs. 7.3 μg/l). In the case of PFOA we observed only minor differences between PFOA concentrations within the analysed sample pairs (median: 2.6 μg/l vs. 3.4 μg/l for maternal and cord plasma samples, respectively). Discussion For both substances a crossing of the placental barrier could be shown. For PFOS we observed a decrease from maternal to cord plasma concentrations by a factor of 0.41–0.80. To the contrary, PFOA crosses the placental barrier obviously unhindered. These findings show that neonates are exposed to PFOS and PFOA via their mothers’ blood. Given the current situation that only little is known about the consequences of PFOS and PFOA exposure in the early state of development of humans and the fact that in animal studies both substances showed developmental toxic effects further research regarding human health effects is indispensable.     

Combined Effects of PFOS and PFOA on Zebrafish (Danio rerio) Embryos

Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) are two kinds of emerging contaminants most studied in recent years. However, there is limited information about their combined toxicity to aquatic organisms. In the present study, the single and combined toxicity of PFOA and PFOS to zebrafish (Danio rerio) embryos were investigated. PFOS was more toxic than PFOA for the single toxicity. In four mixtures, PFOS and PFOA showed complex interactive effects that changed from additive to synergistic effect, then to antagonistic effect, and at last turnover to synergic effect again, with increased molar ratios of PFOS. Neither the concentration-addition model nor the independent-action model could predict the combined effects when strong interactive effects existed. Although the interactive effects of PFOS and PFOA affected their combined toxicity, the trend of mixture toxicity still showed an increase with increasing molar ratios of PFOS in the mixture.     

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.     

Per- and polyfluoroalkyl substances impact human spermatogenesis in a stem-cell-derived model

Per- and polyfluoroalkyl substances (PFASs) represent a highly ubiquitous group of synthetic chemicals used in products ranging from water and oil repellents and lubricants to firefighting foam. These substances can enter and accumulate in multiple tissue matrices in up to 100% of people assessed. Though animal models strongly identify these compounds as male reproductive toxicants, with exposed rodents experiencing declines in sperm count, alterations in hormones, and DNA damage in spermatids, among other adverse outcomes, human studies report conflicting conclusions as to the reproductive toxicity of these chemicals. Using an innovative, human stem-cell-based model of spermatogenesis, we assessed the effects of the PFASs perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and a mixture of PFOS, PFOA, and PFNA for their impacts on human spermatogenesis in vitro under conditions relevant to the general and occupationally exposed populations. Here, we show that PFOS, PFOA, PFNA, and a mixture of PFOS, PFOA, and PFNA do not decrease in vitro germ cell viability, consistent with reports from human studies. These compounds do not affect mitochondrial membrane potential or increase reactive oxygen species generation, and they do not decrease cell viability of spermatogonia, primary spermatocytes, secondary spermatocytes, or spermatids in vitro under the conditions examined. However, exposure to PFOS, PFOA, and PFNA reduces expression of markers for spermatogonia and primary spermatocytes. While not having direct effects on germ cell viability, these effects suggest the potential for long-term impacts on male fertility through the exhaustion of the spermatogonial stem cell pool and abnormalities in primary spermatocytes.

Abbreviations: CDC: Centers for Disease Control; DMSO: dimethyl sulfoxide; GHR: growth hormone receptor; hESCs: human embryonic stem cells; PFASs: per- and polyfluoroalkyl substances; PFCs: perfluorinated compounds; PFNA: perfluorononanoic acid; PFOS: perfluorooctanesulfonic acid; PFOA: perfluorooctanoic acid; PLZF: promyelocytic leukemia zinc finger; ROS: reactive oxygen species; HILI: RNA-mediated gene silencing 2; SSC: spermatogonial stem cell     

Toxicity of perfluorooctane sulfonic acid and perfluorooctanoic acid on freshwater macroinvertebrates (Daphnia magna and Moina macrocopa) and fish (Oryzias latipes)

Because of their global distribution, persistence, and tendency to bioaccumulate, concerns about perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) are growing. We determined the toxicity of PFOS and PFOA in several freshwater organisms, including two cladocerans, Daphnia magna and Moina macrocopa, and the teleost Oryzias latipes. In general, PFOS is approximately 10 times more toxic than PFOA in these organisms. In M. macrocopa, the median lethal concentration (LC50) was 17.95 mg/L for PFOS and 199.51 mg/L for PFOA. Moina macrocopa exhibited greater sensitivity than D. magna to both perfluorinated compounds in both acute and chronic exposures. In the 48-h acute toxicity test, M. macrocopa was approximately two times more sensitive than D. magna. In the 7-d chronic toxicity test, M. macrocopa showed significant reproductive changes at 0.31 mg/L for PFOS, which was approximately seven times lower than the effect concentrations observed over the 21-d exposure in D. magna. Two-generation fish toxicity tests showed that parental exposure to both compounds affected the performance of offspring. Unexposed progeny-generation (F1) fish exhibited elevated mortality and histopathological changes that were correlated with exposure in the parental generation (F0). Continuous exposure from F0 through F1 generations increased the extent of adverse effects. Considering the persistent nature of PFOS and PFOA, more research is required to determine potential consequences of long-term exposure to these compounds in aquatic ecosystems.     

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.     

Cord serum concentrations of perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) in relation to weight and size at birth

BACKGROUND: Recent studies have reported developmental toxicity among rodents dosed with perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA). OBJECTIVES: We examined the relationship between concentrations of PFOS and PFOA in cord serum (surrogates for in utero exposures) and gestational age, birth weight, and birth size in humans. METHODS: We conducted a hospital-based cross-sectional epidemiologic study of singleton deliveries in Baltimore, Maryland. Cord serum samples (n = 293) were analyzed for PFOS and PFOA by online solid-phase extraction, coupled with reversed-phase high-performance liquid chromatography-isotope dilution tandem mass spectrometry. Maternal characteristics and anthropometric measures were obtained from medical charts. RESULTS: After adjusting for potential confounders, both PFOS and PFOA were negatively associated with birth weight [per ln-unit: beta = -69 g, 95% confidence interval (CI), -149 to 10 for PFOS; beta = -104 g, 95% CI, -213 to 5 for PFOA], ponderal index (per ln-unit: beta = -0.074 g/cm(3) x 100, 95% CI, -0.123 to -0.025 for PFOS; beta = -0.070 g/cm(3) x 100, 95% CI, -0.138 to -0.001 for PFOA), and head circumference (per ln-unit: beta = -0.32 cm, 95% CI, -0.56 to -0.07 for PFOS; beta = -0.41 cm, 95% CI, -0.76 to -0.07 for PFOA). No associations were observed between either PFOS or PFOA concentrations and newborn length or gestational age. All associations were independent of cord serum lipid concentrations. CONCLUSIONS: Despite relatively low cord serum concentrations, we observed small negative associations between both PFOS and PFOA concentrations and birth weight and size. Future studies should attempt to replicate these findings in other populations.     

Fetal growth indicators and perfluorinated chemicals: a study in the Danish National Birth Cohort

Perfluorooctanoate (PFOA) and perfluorooctanesulfonate (PFOS) are widespread persistent organic pollutants that have been associated with reduced birth weight at doses expected in many pregnant populations. The authors randomly selected 1,400 pregnant women and their newborns from the Danish National Birth Cohort (1996-2002) to investigate whether these compounds reduce organ growth. PFOS and PFOA were measured in maternal blood samples taken early in pregnancy. Placental weight, birth length, and head and abdominal circumferences were measured shortly after birth by trained midwives or nurses. Maternal PFOA levels in early pregnancy were associated with smaller abdominal circumference and birth length. For each ng/ml increase in PFOA, birth length decreased by 0.069 cm (95% confidence interval: 0.024, 0.113) and abdominal circumference decreased by 0.059 cm (95% confidence interval: 0.012, 0.106). An inverse association was also observed between PFOA and placental weight and head circumference, and a positive association was observed with newborn ponderal index, but none of these associations was statistically significant. Maternal PFOS levels were not associated with any of the five fetal growth indicators. These findings suggest that fetal exposure to PFOA but not PFOS during organ development may affect the growth of organs and the skeleton.