韦荣国;张银凤;秦占芬;

• 1:中国科学院生态环境研究中心环境化学和生态毒理学国家重点实验室

摘要(Abstract)：

全氟化合物(PFCs)在工业生产和生活中广泛应用,已成为环境中一类普遍的污染物。由于PFCs污染表现出全球性、持久性和富集性等特征,其毒性备受关注。近期研究结果显示,PFCs除对肝脏、免疫系统和生殖内分泌系统等有明显影响外,还具有发育神经毒性。在总结了近年来PFCs发育神经毒性的研究进展基础上,讨论了PFCs发育神经毒性可能的几个机制,并且分析该领域研究存在的问题,提出应该加强环境相关剂量下PFCs发育神经毒性研究,关注PFCs与其他神经毒物复合暴露的发育神经毒性,以推进对实际环境中PFCs所产生的神经损伤的认识。

关键词(KeyWords)： 全氟化合物;发育神经毒性;环境相关剂量

Abstract:

Keywords:

基金项目(Foundation): “863”计划课题(2010AA065105);; 国家自然科学基金项目(21077125);; 环保公益专项(201109048)

作者(Author): 韦荣国;张银凤;秦占芬;

Email:

参考文献(References)：

• [1]Paul A G,Jones K C,Sweetman A J.A first global pro-duction,emission,and environmental inventory for perfluorooctane sulfonate[J].Environmental Science&Technology,2009,43(2):386-392
• [2]Kannan K,Choi J W,Iseki N,et al.Concentrations of perfluorinated acids in livers of birds from Japan and Korea[J].Chemosphere,2002,49(3):225-231
• [3]Ostertag S K,Chan H M,Moisey J,et al.Historic diet-ary exposure to perfluorooctane sulfonate,perfluorinat-ed carboxylates,and fluorotelomer unsaturated carbox-ylates from the consumption of store-bought and res-taurant foods for the Canadian population[J].Journal of Agricultural and Food Chemistry,2009,57(18):8534-8544
• [4]Martin J W,Asher B J,Beesoon S,et al.PFOS or Pre-FOS?Are perfluorooctane sulfonate precursors(Pre-FOS)important determinants of human and environ-mental perfluorooctane sulfonate(PFOS)exposure?[J].Journal of Environmental Monitoring,2010,12(11):1979-2004
• [5]Renner R.The long and the short of perfluorinated re-placements[J].Environmental Science&Technology,2006,40(1):12-13
• [6]Cassone C G,Vongphachan V,Chiu S,et al.In ovo effects of perfluorohexane sulfonate and perfluorohex-anoate on pipping success,development,mRNA ex-pression,and thyroid hormone levels in chicken embry-os[J].Toxicological Sciences,2012,127(1):216-224
• [7]Wilhelm M,Bergmann S,Dieter H H.Occurrence of perfluorinated compounds(PFCs)in drinking water of North Rhine-Westphalia,Germany and new approach to assess drinking water contamination by shorter-chained C4-C7PFCs[J].International Journal of Hy-giene and Environmental Health,2010,213(3):224232
• [8]Butenhoff J L,Ehresman D J,Chang S C,et al.Gesta-tional and lactational exposure to potassium perfluo-rooctanesulfonate(K+PFOS)in rats:Developmental neurotoxicity[J].Reproductive Toxicology,2009,27(3-4):319-330
• [9]Huang H,Huang C,Wang L,et al.Toxicity,uptake ki-netics and behavior assessment in zebrafish embryos following exposure to perfluorooctane sulphonic acid(PFOS)[J].Aquatic Toxicology,2010,98(2):139-147
• [10]Wang M,Chen J,Lin K,et al.Chronic zebrafish PFOS exposure alters sex ratio and maternal related effects in F1offspring[J].Environmental Toxicology&Chemis-try,2011,30(9):2073-2080
• [11]Johansson N,Fredriksson A,Eriksson P.Neonatal ex-posure to perfluorooctane sulfonate(PFOS)and perflu-orooctanoic acid(PFOA)causes neurobehavioural de-fects in adult mice[J].Neurotoxicology,2008,29(1):160-169
• [12]Lau C,Thibodeaux J R,Hanson R G,et al.Exposure to perfluorooctane sulfonate during pregnancy in rat and mouse.II:Postnatal evaluation[J].Toxicological Sci-ences,2003,74(2):382-392
• [13]Fuentes S,Colomina M T,Vicens P,et al.Influence of maternal restraint stress on the long-lasting effects induced by prenatal exposure to perfluorooctane sulfonate(PFOS)in mice[J].Toxicology Letters,2007,171(3):162-170
• [14]Onishchenko N,Fischer C,Wan Ibrahim W N,et al.Prenatal exposure to PFOS or PFOA alters motor func-tion in mice in a sex-related manner[J].Neurotoxicity Research,2011,19(3):452-461
• [15]Luebker D J,Case M T,York R G,et al.Two-genera-tion reproduction and cross-foster studies of perfluo-rooctanesulfonate(PFOS)in rats[J].Toxicology,2005,215(1-2):126-148
• [16]Fuentes S,Vicens P,Colomina M T,et al.Behavioral effects in adult mice exposed to perfluorooctane sulfon-ate(PFOS)[J].Toxicology,2007,242(1-3):123-129
• [17]Pinkas A,Slotkin T A,Brick-Turin Y,et al.Neurobe-havioral teratogenicity of perfluorinated alkyls in an a-vian model[J].Neurotoxicology and Teratology,2010,32(2):182-186
• [18]Slotkin T A,MacKillop E A,Melnick R L,et al.De-velopmental neurotoxicity of perfluorinated chemicals modeled in vitro[J].Environmental Health Perspec-tives,2008,116(6):716-722
• [19]Liao C Y,Li X Y,Wu B,et al.Acute enhancement of synaptic transmission and chronic inhibition of synap-togenesis induced by perfluorooctane sulfonate through mediation of voltage-dependent calcium channel[J].Environmental Science&Technology,2008,42(14):5335-5341
• [20]Peden-Adams M M,Stuckey J E,Gaworecki K M,et al.De-velopmental toxicity in white leghorn chickens following in ovo exposure to perfluorooctane sulfonate(PFOS)[J].Re-productive Toxicology,2009,27(3-4):307-318
• [21]Zhang L,Li Y Y,Zeng H C,et al.Perfluorooctane sulfonate induces apoptosis in N9microglial cell line[J].International Journal of Toxicology,2011,30(2):207-215
• [22]Johansson N,Eriksson P,Viberg H.Neonatal exposure to PFOS and PFOA in mice results in changes in pro-teins which are important for neuronal growth and syn-aptogenesis in the developing brain[J].Toxicological Sciences,2009,108(2):412-418
• [23]Zeng H C,Zhang L,Li Y Y,et al.Inflammation-like glial response in rat brain induced by prenatal PFOS ex-posure[J].Neurotoxicology,2011,32(1):130-139
• [24]Zeng H C,Li Y Y,Zhang L,et al.Prenatal exposure to perfluorooctanesulfonate in rat resulted in long-lasting changes of expression of synapsins and synaptophysin[J].Synapse,2011,65(3):225-233
• [25]Li Y,Jin Y H.Effects of perfluorooctane sulfonylsulfonate on glutamate concentration of central nervous system in rats[J].Journal of Health Toxicology,2004,18(4):232-234
• [26]王柯,金一和,于棋麟,等.全氟辛烷磺酸对小鼠大脑谷氨酸含量和蛋白激酶活性的影响[J].中华预防医学杂志,2007,41(6):466-470Wang K,Jin Y H,Yu Q L,et al.Effects of perfluo-rooctane sulfonate on Glu,PKC and PKA activities in mouse brain[J].Zhonghua Yu Fang Yi Xue Za Zhi,2007,41(6):466-470.
• [27]Liu C,Yu K,Shi X,et al.Induction of oxidative stress and apoptosis by PFOS and PFOA in primary cultured hepatocytes of freshwater tilapia(Oreochromis nilotic-us)[J].Aquatic Toxicology,2007,82(2):135-143
• [28]Hu X Z,Hu D C.Effects of perfluorooctanoate and perfluorooctane sulfonate exposure on hepatoma HepG2cells[J].Archives of Toxicology,2009,83(9):851-861
• [29]Lee H G,Lee Y J,Yang J H.Perfluorooctane sulfonate induces apoptosis of cerebellar granule cells via a ROS-dependent protein kinase C signaling pathway[J].Neu-rotoxicology,2012,33(3):314-320
• [30]Shi X,Du Y,Lam P K,et al.Developmental toxicity and alteration of gene expression in zebrafish embryos exposed to PFOS[J].Toxicology and Applied Pharma-cology,2008,230(1):23-32
• [31]Shi X,Yeung L W,Lam P K,et al.Protein profiles in zebrafish(Danio rerio)embryos exposed to perfluo-rooctane sulfonate[J].Toxicological Sciences,2009,110(2):334-340
• [32]Yang H,Dong H S,Lin Y L,et al.Research progress of protein kinase C in neuroprotection[J].Medical Reca-pitulate,2009,15(18):2736-2738
• [33]刘冰,于麒麟,金一和,等.全氟辛烷磺酸对大鼠海马神经细胞内钙离子浓度的影响[J].毒理学杂志,2005,19(S1):225
• [34]Liu X,Liu W,Jin Y,et al.Effects of subchronic perflu-orooctane sulfonate exposure of rats on calcium-de-pendent signaling molecules in the brain tissue[J].Ar-chives of Toxicology,2010,84(6):471-479
• [35]Liao C Y,Cui L,Zhou Q F,et al.Effects of perfluo-rooctane sulfonate on ion channels and glutamate-acti-vated current in cultured rat hippocampal neurons[J].Environmental Toxicology and Pharmacology,2009,27(3):338-344
• [36]Liu X,Jin Y,Liu W,et al.Possible mechanism of per-fluorooctane sulfonate and perfluorooctanoate on the release of calcium ion from calcium stores in primary cultures of rat hippocampal neurons[J].Toxicology in Vitro,2011,25(7):1294-1301
• [37]Haddow J E,Palomaki G E,Allan W C,et al.Maternal thyroid deficiency during pregnancy and subsequent neu-ropsychological development of the child[J].New Eng-land Journal of Medicine,1999,341(8):549-555
• [38]Zoeller R T,Crofton K M.Mode of action:develop-mental thyroid hormone insufficiency--neurological ab-normalities resulting from exposure to propylthiouracil[J].Critical Reviews in Toxicology,2005,35(8-9):771-781
• [39]Austin M E,Kasturi B S,Barber M,et al.Neuroendo-crine effects of perfluorooctane sulfonate in rats[J].Environmental Health Perspectives,2003,111(12):1485-1489
• [40]Chang S C,Thibodeaux J R,Eastvold M L,et al.Thy-roid hormone status and pituitary function in adult rats given oral doses of perfluorooctanesulfonate(PFOS)[J].Toxicology,2008,243(3):330-339
• [41]Wang F,Liu W,Jin Y,et al.Interaction of PFOS and BDE-47co-exposure on thyroid hormone levels and TH-related gene and protein expression in developing rat brains[J].Toxicological Sciences,2011,121(2):279-291
• [42]Vongphachan V,Cassone C G,Wu D,et al.Effects of perfluoroalkyl compounds on mRNA expression levels of thyroid hormone-responsive genes in primary cul-tures of avian neuronal cells[J].Toxicological Sciences,2011,120(2):392-402
• [43]Myers J P,Zoeller R T,vom Saal F S.A clash of old and new scientific concepts in toxicity,with important implications for public health[J].Environmental Health Perspectives,2009,117(11):1652-1655
• [44]Andrade A J,Grande S W,Talsness C E,et al.A dose-response study following in utero and lactational expo-sure to di-(2-ethylhexyl)-phthalate(DEHP):Non-mon-otonic dose-response and low dose effects on rat brain aromatase activity[J].Toxicology,2006,227(3):185-192
• [45]Narita S,Goldblum R M,Watson C S,et al.Environmental estrogens induce mast cell degranulation and enhance IgE-mediated release of allergic mediators[J].Environmental Health Perspectives,2007,115(1):48-52
• [46]Lau C,Thibodeaux J R,Hanson R G,et al.Effects of perfluorooctanoic acid exposure during pregnancy in the mouse[J].Toxicological Sciences,2006,90(2):510-518
• [47]Jacquet N,Maire M A,Landkocz Y,et al.Carcinogenic potency of perfluorooctane sulfonate(PFOS)on Syrian hamster embryo(SHE)cells[J].Archives of Toxicolo-gy,2012,86(2):305-314
• [48]Dorts J,Kestemont P,Marchand P A,et al.Ecotoxi-coproteomics in gills of the sentinel fish species,Cottus gobio,exposed to perfluorooctane sulfonate(PFOS)[J].Aquatic Toxicology,2011,103(1-2):1-8
• [49]Birnbaum L S.Applying research to public health ques-tions:timing and the environmentally relevant dose[J].Environmental Health Perspectives,2009,117(11):1652-1655
• [50]Newsted J L,Beach S A,Gallagher S P,et al.Acute and chronic effects of perfluorobutane sulfonate(PFBS)on the mallard and northern bobwhite quail[J].Archives of Environmental Contamination and Toxicology,2008,54(3):535-545
• [51]Wolf C J,Takacs M L,Schmid J E,et al.Activation of mouse and human peroxisome proliferator-activated re-ceptor alpha by perfluoroalkyl acids of different func-tional groups and chain lengths[J].Toxicological Sci-ences,2008,106(1):162-171
• [52]Foreman J E,Chang S C,Ehresman D J,et al.Differ-ential hepatic effects of perfluorobutyrate mediated by mouse and human PPAR-alpha[J].Toxicological Sci-ences,2009,110(1):204-211
• [53]Calafat A M,Wong L Y,Kuklenyik Z,et al.Polyflu-oroalkyl chemicals in the U.S.population:Data from the National Health and Nutrition Examination Survey(NHANES)2003-2004and comparisons with NHANES1999-2000[J].Environmental Health Perspectives,2007,115(11):1596-1602
• [54]Naile J E,Wiseman S,Bachtold K,et al.Transcription-al effects of perfluorinated compounds in rat hepatoma cells[J].Chemosphere,2012,86(3):270-277
• [55]Scialli A R,Iannucci A,Turim J.Combining perfluoro-alkane acid exposure levels for risk assessment[J].Reg-ulatory Toxicology and Pharmacology,2007,49(3):195-202
• [56]Fromme H,Albrecht M,Angerer J,et al.Integrated exposure assessment survey(INES)exposure to persistent and bioaccumulative chemicals in Bavaria,Germany[J].International Journal of Hygiene and Environmental Health,2007,210(3-4):345-349
• [57]Wei Y,Shi X,Zhang H,et al.Combined effects of polyfluorinated and perfluorinated compounds on pri-mary cultured hepatocytes from rare minnow(Gobio-cypris rarus)using toxicogenomic analysis[J].Aquatic Toxicology,2009,95(1):27-36
• [58]Dorne J L C M,Bordajandi L R,Amzal B,et al.Com-bining analytical techniques,exposure assessment and biological effects for risk assessment of chemicals in food[J].Trends in Analytical Chemistry,2009,28(6):695-707
• [59]Nakayama K,Iwata H,Tao L,et al.Potential effects of perfluorinated compounds in common cormorants from Lake Biwa,Japan:An implication from the he-patic gene expression profiles by microarray[J].Envi-ronmental Toxicology&Chemistry,2008,27(11):2378-2386
• [60]Fei C,Olsen J.Prenatal exposure to perfluorinated chemicals and behavioral or coordination problems at age7years[J].Environmental Health Perspectives,2011,119(4):573-578
• [61]Wang F,Liu W,Jin Y,et al.Transcriptional effects of prenatal and neonatal exposure to PFOS in developing rat brain[J].Environmental Science&Technology,2010,44(5):1847-1853
• [62]Kozul C D,Ely K H,Enelow R I,et al.Low-dose arse-nic compromises the immune response to influenza an infection in vivo[J].Environmental Health Perspec-tives,2009,117(9):1441-1447
• [63]Bardullas U,Limon-Pacheco J H,Giordano M,et al.Chronic low-level arsenic exposure causes gender-spe-cific alterations in locomotor activity,dopaminergic systems,and thioredoxin expression in mice[J].Toxi-cology and Applied Pharmacology,2009,239(2):169-177