摘要
环境内分泌干扰物对人和动物的影响已成为国际性热门问题,尤其是环境雌激素通过与雌激素受体结合或影响细胞信号传导途径或其他方式模仿和干扰内源性雌激素作用,发挥拟雌激素样效应,对人类和动物造成很大的危害。双酚A(BPA)是制造环氧树脂、聚碳酸酯树脂、聚苯乙烯树脂的主要原料,又用于酚醛树脂、杀菌剂、抗氧化剂、聚氯乙烯、染料等的稳定剂。烷基酚壬基酚(NP)、辛基酚(OP)被广泛地用作塑料增塑剂、工业用洗涤剂、农药乳化剂、纺织行业的整理剂。
人们生活中广泛用到以BPA、NP和OP为原料生产的物品,BPA、NP和OP会被迁移,污染人们的日常生活环境,尤为严重的是在食品包装中加入的BPA、NP和OP会溶入食品,而直接进入人体,危害人类健康。我国是BPA、NP和OP的使用大国,如果不严格控制,由BPA、NP和OP造成的污染问题将会非常严重。为了更好地保护我国人群健康以及国家的产业利益,本文对罐装食品中BPA、NP和OP的检测技术、尿液中的生物标志物和塑料制品的迁移等进行了较系统的研究,同时对人群摄入BPA、NP和OP的暴露进行评估。
(1)罐装食品中BPA、NP和OP的检测方法建立与应用
运用固相萃取、液液萃取等前处理方法,结合超高压液相色谱—质谱/质谱(UPLC—MS/MS)或高效液相色谱—荧光检测(HPLC—FLD)分析手段,建立检测罐装食品中BPA、NP和OP含量的方法。固体样品经甲醇超声提取、蒸干,溶解于碱性溶液中,酸化,用二氯甲烷萃取、浓缩。液体样品的分析采用NH_2柱浓缩、富集和净化。UPLC采用的色谱柱是粒径为1.7μm的AcquityUPLCT~(TM) BEH,C_(18)柱;甲醇-水作为流动相梯度洗脱,质谱仪采用三重四极杆质量分析器定性定量分析。该方法BPA、NP和OP在蔬菜、鱼和肉罐头样品中的检出限范围为0.22-0.35μg/kg、0.031-0.050μg/kg和0.08-0.12μg/kg,定量限分别为0.55-0.80μg/kg、0.10-0.94μg/kg和0.20-0.30μg/kg。BPA、NP和OP的加标回收率分别为70.0-120%、70.2-120%和71.2-133%;BPA、NP和OP的相对标准偏差分别为7.06-17.6%、4.49-18.9%和6.91-19.2%。
HPLC使用的色谱柱是Waters Xterra MS(?)C18柱,采用荧光检测,甲醇-水作为流动相梯度洗脱。采用荧光检测,激发波长:225nm;发射波长:310nm。该方法BPA、NP和OP的检出限分别为0.52-0.91μg/kg、0.10-0.52μg/kg和0.14-0.53μg/kg,定量限分别为1.18-2.70μg/kg、0.28-2.15μg/kg和0.35-1.87μg/kg。BPA、NP和OP的加标回收率分别为70.1-90.2%、80.1-122%和72.1-126%;BPA、NP和OP的相对标准偏差分别为5.61-11.2%、2.35-8.88%和5.61-12.3%。
本研究分别采用以上两种检测方法,对北京市售的30份食品进行了检测。两种方法均实现了BPA、NP和OP三种物质的同时测定,HPLC—FL法具有较高的灵敏度、准确度、精密度和特异性,符合食品中BPA、NP和OP的痕量分析要求,但应采用UPLC-MS/MS方法进行确证
(2)人尿中BPA、NP和OP代谢产物的检测方法建立与应用
双酚A、壬基酚和辛基酚在尿中的代谢产物主要是葡萄糖苷结合物和硫酸酯结合物及少量原型。本文在建立相应的检测方法的基础上,对普通人群的尿液中BPA、NP和OP含量进行检测。
采用β-葡萄糖酸酐酶、硫酸酯酶水解人尿液中的结合型BPA、NP和OP,酶解后溶液采用OASIS HLB固相萃取柱浓缩、富集和净化。处理后的样品采用UPLC—MS/MS或HPLC-FL检测,建立了检测尿液中BPA、NP和OP含量的方法。
UPLC—MS/MS方法BPA、NP和OP的检测限分别为0.41μg/L、0.20μg/L和0.50μg/L;定量限分别为1.02μg/L、0.85μg/L和1.28μg/L;加标回收率分别为72.3-109%、71.2-114%和76.6-116%;相对标准偏差分别为12.5-14.1%、10.0-14.0%和7.12-15.5%。
HPLC-FL方法BPA、NP和OP的检测限分别为3.71μg/L、4.90μg/L和7.50μg/L;定量限分别为11.9μg/L、15.7μg/L和21.3μg/L;加标回收率分别为70.2-95.7%、73.2-108%和76.3-109%;相对标准偏差分别为8.81-10.7%、9.31-14.5%和6.65-15.5%。
采用这两种检测方法,对健康人群的60份尿液进行了检测。
(3)塑料制品的迁移实验研究
双酚A、壬基酚和辛基酚可用于生产非离子表面活性剂、增塑剂、聚碳酸酯、环氧树脂、聚砜树脂、聚苯醚树脂、不饱和聚酯树脂等高分子材料,被广泛用于制造塑料制品、食具、涂层等。国内外有文献报道,从这类制品中溶出微量BPA、NP和OP,对人体健康及环境污染造成威胁,直接影响道人的身体健康。
本文建立了塑料制品中辛基酚、壬基酚和双酚A迁移量的UPLC—MS/MS测定方法。该方法的BPA、NP和OP检出限分别为0.25-0.38μg/L、0.10-0.22μg/L和0.20-0.30μg/L;定量限为0.70-1.01μg/L、0.50-0.74μg/L和0.75-0.80μg/L。BPA、NP和OP的加标回收率分别为80.1-105%、80.8-112%和80.5-110%,相对标准偏差分别为5.02-10.9%、4.66-13.5%和4.73-10.4%。
同时也建立了塑料制品中辛基酚、壬基酚和双酚A迁移量的HPLC—FL测定方法。该方法的BPA、NP和OP出限分别为1.55-2.75μg/L、1.00-1.60μg/L和1.00-1.84μg/L;定量限为4.03-5.00μg/L、2.85-3.41μg/L和2.75-4.05μg/L。BPA、NP和OP的加标回收率分别为80.9-107%、80.4-108%和80.4-107%,相对标准偏差分别为4.24-11.5%、4.93-12.4%和3.64-9.88%。
用以上方法分别考察了不同条件下的迁移情况,包括不同浸泡液:蒸馏水、3%醋酸、4%醋酸、15%乙醇、20%乙醇、65%乙醇、正己烷;不同温度:室温、水浴40℃、60℃、80℃、100℃;不同浸泡时间:12h、24h和48h。结果表明,当模拟物为65%乙醇,60℃水浴浸泡3小时时,检测到BPA、NP和OP迁移量最大。因此,选用模拟物65%乙醇,60℃沸水浴浸泡3小时为迁移检测条件。
(2)BPA、NP和OP的测定及其暴露评估
30份罐装食品(10份蔬菜罐头、10份鱼罐头、10份肉罐头)中11份检出BPA,其含量水平为0.180-12.3μg/kg;27份检出了NP,其含量水平为1.35-100μg/kg;6份检出了OP,其含量水平为0.05-23.5μg/kg。此结果表明,壬基酚NP广泛存在于罐装食品中。
在被检的60人份尿样中,8份检出BPA,占13.3%,暴露水平为0.515-49.5ng/ml;29份检出NP,占48.3%,暴露水平为2.32-28.5 ng/ml;17份检出OP,占28.3%,暴露水平为0.720-15.2ng/ml。女性检出率高于男性检出率,但不同年龄组间检出率差别不大。
被检的塑料饭盒、奶瓶、水杯、油壶等15种塑料制品中,13份检出BPA,其迁移量为10.3-1004ng/L;14份检出NP,其迁移量为103-9875ng/L;5份检出。应考虑累积的环境暴露是伤害我们健康的OP,其迁移量为1.02-12.1ng/L。此结果表明,塑料制品存在双酚A、壬基酚和辛基酚的迁移。迁移条件(温度、溶剂和贮存时间)不同,迁移量也不同。
虽然在众多样品中检出了双酚A、壬基酚和辛基酚,暴露水平远低于文献报道的毒性阀值。但是,由于双酚A、壬基酚和辛基酚广泛存在于各种环境介质中,累积的环境暴露对我们的健康仍然存在较大的风险。
The influence of environment endocrine(内分泌)interference to the person and the animal was becoming an international popular problem.Particularly,the environment estrogen(雌激素)initiated and interfered endogenesis estrogen by combining with estrogenic receptor or influencing the way of cell signal conduction or the other ways,which has esteogen-like action,brings hazard to the mankind and the animal.BPA was key raw material of making epoxide resin、polycarbonate、polystyrene resin,which was used to the stabilizing of agent phenol formaldehyde resin、bactericidal agen、antioxidanK polyvinyl chloride、dye.The alkylphenol NP、OP was widely used to elasticizer、technica grade abstergent、pesticide emulsifies、trimming Iin the spinning and weaving,ect.
People usually use some articles,whose raw material was BPA、NP and OP, BPA、NP and OP were often migrated and contaminate living environment .Especially,BPAn、NP and OP were migrated to food when food packing has BPA、NP and OP,enter a human body directly,endanger mankind's health.Our country is important country using BPA、NP and OP,if we didn't control strictly,the pollution problem of the BPA,NP and OP would be very serious.For the sake of the protection our country people health and the industry benefits of the nations, we carried on detection technique、organism marker and migration of plastic products of BPA、NP and OP,and make a comprehensive comment to the BPA,NP and OP in the meantime,mainly include several aspects as follows:
(1)The detection technique of the BPA,NP and OP in the canned food
In this study,the comprehensive analytical methods based on Ultra-high Pressure Liquid Chromatography-mass/mass(UPLC-MS/MS)or high performance liquid chromatography fluorescence detection(HPLC-FLD)with solid phase extraction,Liquid liquid Extraction before have been established for determination of BPA,NP and OP in food samples
BPA,NP and OP was extracted with methanol,the residue was dissolved in alkaline solution,acidized,extracted by dichloroacetamide from the foods and the extract was concentrated.Clean-up of samples was performed on an NH_2 column solid extraction cartridges.
The UPLC separation was performed on a Acquity UPLC~(TM) BEH,C_18 column(particle diameter 1.7μm) with a gradient elution system of methanol-water as the mobile phase.triple-quadrupole mass spectrometry analyzer was performed for the qualitative and quantitative analyse of LC-MS/MS system.The limit of detection of BPA、NP and OP was 0.22-0.35μg/kg、0.031-0.05Oμg/kg and 0.08-0.12μg/kg;The limit of quantification of BPA,、NP and OP was0.55-0.80μg/kg、0.10-0.94μg/kg and 0.20-0.30μg/kg;The Recoveries of BPA,NP and OP were 70.0-123%,70.2-125%and 71.2-133%;The precision was 7.06-17.6%,3.98-18.9%and 6.91-19.2%,respectively.
The HPLC separation was performed on Waters XTerra~? MS C_18 column with a gradient elution system of methanol-water as the mobile phase and fluorescence detector with the excitation and emission wavelength at 225 nm and 310nm respectively were used for the determination..The limit of detection of BPA、NP and OP was 0.52-0.91μg/kg、0.10-0.52μg/kg and 0.14-0.53μg/kg;The limit of quantification of BPA、NP and OP was 1.18-2.70μg/kg、0.28-2.15μg/kg and 0.35-1.87μg/kg;The Recoveries of BPA、NP and OP were 70.1-90.2%、80.1-122%and 72.1-126%;The precision was 5.61-11.2%、2.35-8.88%and 5.61-12.3%,respectively.
The two methods both may detect the BPA,NP and OP at the time,The results showed that the method is with high sensitivity、accuracy、precision、specificity.the method is suitable for the determination of BPA、NP and OP in can food.30 food samples from Beijing's markets were determined by using the improved methods,the method is simple,the result is accurate、credibility.
(2)The study of biomarker-human urine The BPA,NP and OP is esteogen-like "endocrine chemical materials".the general people contacted with the BPA,NP and OP through using plastics packing material、the can food、abstergent,ect.The metabolic product in urine is mainly glucoside conjugate and sulphate conjugate.In this study,we detected BPA,NP and OP in the urine of health crowd.
The urine samples was de-conjugated by addingβ-glucuronidase and sulfatase,after the enzymatic treatment,the samples was subjected to the OASIS HLB column solid extraction cartridges to Clean-up and concentrate.
A comprehensive analytical method based on Ultra-high Pressure Liquid Chromatography-mass/mass(UPLC-MS/MS)or high performance liquid chromatography fluorescence detection(HPLC-FLD) has been established for the determination of BPA,NP and OP in urine.
UPLC-MS/MS:The limit of detection of BPA、OP and NP was 0.41、0.20 and 0.50μg/L;The limit of quantification of BPA、OP and NP was 1.02、0.85 and 1.28μg/L;The Recoveries of BPA、OP and NP were 72.3-109%、71.2-114%、76.6-116%;The precision was 12.5-14.1%、10.0-14.0%、7.12-15.5%,respectively.
HPLC-FL:The limit of detection of BPA、OP and NP was 3.71、4.90 and 7.50μg/L;The limit of quantification of BPA、OP and NP was 11.9、15.7 and 21.3μg/L;The Recoveries of BPA、OP and NP were 70.2-95.7%、73.2-108%and 76.3-109%;The precision was 8.81-10.7%、9.31-14.5%and 6.65-15.5% respectively.
60 urine samples were determined by using these two methods,the method is sensitivity,selectivity and good reproducibility.
(3) The migration experiment research of the plastics product BPA、OP and NP were one kind of environment estrogen,which were used to make non-ion surface activity agent、elasticizer、polycarbonate、epoxy resin、polysulfone resin、polyphenyl Ether resin、selectron,ect.They were generally used to make plastic products、tableware、coating,ect.According to documents,many plastic products may dissolute a little BPA、OP and NP,brought threat to the human body health and pollute the environment,influence directly the person's healthy.
This study investigated migration circumstance,respectively,under different test conditions:the different simulant:Distilled water、3%acetic acids、4%acetic、 acids、15%alcohol、20%alcohol、65%alcohol、hexane;the different temperature: 25°C、40°C、60°C、80°C、100°C;The Different soaks time:12h、24h and 48h.The result show,when the simulant is 65%alcohol、at 60°C、soak for 3 hours,the amount of migration is greatest.
A UPLC-MS/MS method was developed for quantifying levels of BPA、OP and NP in plastic products.The limit of detection of BPA、OP and NP was 0.25-0.38μg/L、0.10-0.22μg/Land 0.20-0.30μg/L;The limit of quantification of BPA、OP and NP was 0.70-1.01μg/L.0.50-0.74μg/L and 0.75-0.80μg/L;The Recoveries of BPA、OP and NP were 80.1-105%、80.8-112%and 80.5-110%.The precision was 5.02-10.9%.4.66-13.5%and 4.73-10.4%respectively.
A HPLC-FL method was developed for detecting levels of BPA、OP and NP in plastic products.The limit of detection of BPA、OP and NP was 1.55-2.75μg/L、1.00-1.60μg/Land 1.00-1.84μg/L;The 1imit of quantification of BPA、OP and NP was 4.03-5.00μg/L、2.85-3.41μg/L and 2.75-4.05μg/L;The Recoveries of BPA、OP and NP were 80.9-107%、80.4-108%and 80.4-107%.The precision was 4.24-11.5%、4.93-12.4%and 3.64-9.88%respectively.
The experiment showed that the amount of migration is greatest when the sample was soaked in 65%alcohol(60°C)for 3 hours.The method was sensitivity、selectivity、accurate and credibility.
(4) The determination and the exposure assessment of the BPA,NP and OP Using the improved methods established in this work,the BPA,NP and OP in vegetable,fish,meat can food samples from Beijing's markets were determined.We collect 30 can food samples(10 vegetable samples、10 vegetable samples and 10 vegetable samples).11 samples of the total were found to contain BPA,its level is 0.180-12.3μg/kg;27 samples of the total were found to contain NP,its level is 1.35-100μg/kg;6 samples of the total were found to contain OP,its level is 0.05 -23.5μg/kg.The results demonstrated the widespread occurrence of NP in can food.
60 urine samples were determined by using the method,the method is sensitivity、selectivity and good reproducibility.8 samples of the total were found to contain BPA(13.3%),its level is0.515-49.5μg/ml;29 samples of the total were found to contain NP(48.3%),its level is 2.32-28.5 ng/m1;17 samples of the total were found to contain NP(28.3%),its level is 0.720-15.2ng/ml.The female detection ratios was higher the male detection ratios.The detection ratios increased with the age increase.
15 plastics product samples(plastics box、baby's bottle、water cup and lubricator)were determined 13 samples of the total were found to contain BPA,its level is 10.3-1004ng/L;14 samples of the total were found to contain NP,its level is 103 -9875ng/L;5 samples of the total were found to contain OP,its level is 1.02-12.1 ng/L.
The results demonstrated many samples contained BPA,NP and OP,and NP was resided widely in can food and plastic products.
引文
[1]逄兵,吴向东,任道风,等.双酚A对大鼠睾丸Leyding细胞的毒性作用[J].卫生毒理学杂志,2000,14(3):173-174
[2]靳翠红,赵剑,金一和,等.双酚A对雄性小鼠生殖系统的影响[J].卫生毒理学杂志,2002,16(1):39-42
[3]董黎,杨晓燕,刘继文.辛基酚对雄性大鼠性腺和血清性激素的影响[J].新疆医科大学学报.2004,27(3):231-233
[4]Effects of endocrine disruptors on prosobranch snail(Mollusca:Gastropoda)in the laboratory.Part I:Bisphenol A and octylphenol as xenoestrogens[J].Ecotoxicology,2000,9:383-397
[5]邓茂先,吴德生,陈祥贵,等.双酚A雄性生殖毒性的体内外实验研究[J].中华预防医学杂志,2004,38(6):383-387
[6]邓茂先,吴德生,詹立.环境雌激素双酚A的生殖毒理研究[J].环境与健康杂志,2001,18(3):134-136
[7]Mohammad A,Awal,Masamichi Kurohmaru,etal.Effect of Bisphenol-A on the Sertoli Cell Culture from Prepubertal Male Wistar Rats.Asian[J].Net work for Scientific in formation,2002,2(1):19-23
[8]段志文,张玉敏,崔金山.双酚A对雄性大鼠睾丸组织某些生化指标的影响[J].毒理学杂志,2005,19(3,增刊):189-190
[9]Ddds EC.Lawson W.Molecular structure in relation to oestrogenic activity.Compounds without a phenathrene nucleus[J].Proc Roy Soc B,1938,125:222-232
[10]Anonymous.Reproductive toxicology.Bisphenol A[J].Environ Health Perspect,1997,105(1):273-274
[11]Matthews JB,Twomey K,Zacharewski TR.In vitro and in vivo interaction of bisphenol A and its metabolite,bisphenol A glucuronide,with estrogen receptors alpha and beta[J].Chem Res Toxicol,2001,14(2):149-157
[12]Hardin BD.Bond GP.Sikon MR,etal.Testing of select workplace chemicals for teratogenic potential.[J].Scand J Wwork Environ Health,1981,7(4):66-75
[13]Akita M,Yokoyama A,Shimizu S,etal.Effects ofBisphenol A on cultured rat embryos[J].Teratology,2000,62(3):15A
[14]Masaharu Akita,Atsushi Yokoyama,Yukiaki Kuroda.Study of Altematives to Testing for Endocrine Disrupters in Rat Whole Embryo Culturetes[J].Forth World Congress,2002,8:11-15
[15]龙鼎新,李小玲,李勇,等.应用全胚胎培养模型研究双酚A的胚胎毒性[J].美国中华临床医学杂志,2002,4(4):264-266
[16]Tomohiro Oka,Naoki Adati,Tadashi Shinkai,etal.Bisphenol A induces apoptosis in central cells during early development of Xenopus laevis[J].Biochemical and Biophysical Research Communication,2003,312(4):877-882
[17]李勇,裴新荣,龙鼎新,等.双酚A对植入后大鼠、小鼠胚胎致畸性的体外实验研究[J].卫生研究,2003,32(2):89-92
[18]生育健康杂志,2003,14(1):34-37
[19]李勇,龙鼎新,裴新荣.采用微团培养技术探讨双酚A的体外发育毒性[J].卫生研究,2002,31(3):178-179
[20]龙冬梅,程薇波,张浩,等.围生期双酚A暴露对断乳期雄性子代脑芳香化酶表达的影响[J].西南国防医药,2005,15(2):123-125
[21]龙冬梅,张浩,程薇波,等.围生期双酚A暴露对F1雄性子代大鼠脑发育的影响[J].环境与健康杂志,2005,22(4):258-261
[22]TabataA,etal.[J]Water Sci Technol,2001,43(2):109-116
[23]Mosconi G,Carnevali O,Franzoni MF,etal.Environmental estrogens and reproductive biology in amphibians.[J]Gen Comp Endocrinol,2002,126(2):125 129.
[24]范奇元,李卫华,申立军,等.壬基酚对S D雄性大鼠生殖功能的影响[J].卫生毒理学杂志,2001,15(4):225 226.
[25]De Jager C,Bornman MS,Oosthuizen JM.The effect of pnonylphenol on the fertility potential of male rats after gestational,lactational and direct exposure.[J]Andrologia,1999,31(2):107-113.
[26]Lauren zana EM,Bala subrama nian G,Weis C,etal.Effect of nonylphenol on serum test oster one levels and testicular steroid ogenic enzyme activity in neonatal,pubertal,and adult rats.[J]Chem Biol Interact,,2002,139(1):23 41.
[27]Laurenzanz EM,Weis CC,Bryant CW.etal.Effect of dietary administration of genisein,nonylphenol or ethinylestradiolon hepatic test osterone metabolism,cytochrome P450enzymes,and estrogen recepe oral pha expression[J]Food Chem Toxicol,2002,.40(1):53-63.
[28]崔金山,张玉敏,段志文,等.双酚A与壬基酚混合染毒对小鼠生精功能的影响[J].工业卫生与职业病,2004,30(5):289-292
[29]张玉敏,崔金山,段志文,等.环境雌激素双酚A对小鼠生精功能的影响[J].工业卫生与职业病,2004,30(5):296-299
[30]Gronen S,etal.[J]Environ Health Perspect,1999,107(5):385 390.
[31]Bayley M,etal.[J]Ecotoxicol Environ Saf,l999,43(1):668 733.
[32]Yoshida M,etal.[J]Toxicol Lett,2001,121(1):21 33.
[33]Murono EP,etal.[J]Reprod Toxicol,1999,13(6):451 462.
[34]Boockfor FR,etal.[J]FundamAppl Toxicol,1997,36:361.
[35]Bicknell RJ,etal.[J].Steroid Biochem Mol Biol 1995,54:7-9.
[36]CharlesA,etal.[J].Toxicol Pharmacol,1997,216(3):446 451.
[37]Katsuda S,etal.[J].Toxicol Pharmacol,2000,165:217-226.
[38]Yoshida M,etal.[J].Toxicol Lett,2000,116(12):89-101.
[39]鲁英,杨晓燕,刘继文.辛基酚对雌性大鼠生殖能力的影响[J].新疆医科大学学报 2005,28(5):394-398
[40]NTP.Carcinogenesis bioassay of bisphenol A(CAS No.80-05-7)in F344 rats and B6C3F1mice(feed study)[J].National Toxicology Program,Technical Report Series,1982,215:1-116
[41]Samuelsen M,Olsen C,Holme JA,etal.Estrogen-like properties of brominated analogs of bisphenol A in the MCF-7 human breast cancer cell line][J].Cell Bio Toxicol,2001,17:139.151
[42]马春艳,郭丽丽,梁前进,等.双酚-A和17b-雌二醇对人乳腺癌细胞生长的影响[J].中国环境科学2002,22(5):408-411
[43]余增丽,张立实,程微波,等.双酚A对PE04卵巢癌细胞凋亡的影响及其作用机制研究[J].西部医学,2003,1(1):3-4
[44]郑继翠,肖现民,刘江斌,等.双酚A对人神经母细胞瘤SK-N-SH细胞增殖的影响[J].中华小儿外科杂志,2006,27(2):90-92
[45]Lois A,Haighton,Jason J.An Evaluation of the Possible Carcinogenicity of Bisphenol A to Humans[J].Regulatory Toxicology and Pharmacology,2002,35(2):238-254
[46]Okai Y,etal.[J]F EMS Microbiol Lett,2000,185(1):65-70.
[47]余楠,舒为群,朱毅.环境雌激素辛基酚对人MCF-7细胞凋亡调控基因bcl-2mRNA表达的影响[J].环境与健康杂志,2002,19(5):358-360
[48]彭俊华,糜漫天,朱俊东,等.辛基酚和三羟异黄酮对二甲基苯蒽诱发大鼠乳腺肿瘤的影响[J]第三军医大学学报2005,27(23):2317-2320
[49]王斌,糜漫天,彭俊华,等.辛基酚和三羟异黄酮对大鼠乳腺癌发生及细胞增殖影响的研究[J]第三军医大学学报,2005,27(2):119-122
[50]朱毅,舒为群,田怀军,等.辛基酚体外类雌激素效应观察[J]第三军医大学 学报,2003,25(8).:673-675
[51]Katsuda S,etal.[J]Jpn J cancer Res,,2002,93(2):117-124.
[52]As cheng rauA,etal.[J]Am J Ind Med,1998,34(1):6-14.
[53]余增丽,张立实,吴德生,等.双酚A等化学物对耗尽内源性雌激素诱导T 47 D细胞凋亡的影响[J].中华预防医学杂志,2003,37(6):3-4
[54]朱毅,舒为群,田怀,等.壬基酚体外类雌激素活性评价及其作用.[J]西南国防医药2003,13(2):119-123
[55]Refetoff S,Weiss RE,Usala SJ,etal,The syndromes of resistance to thyroid hormone[J].Endocr Rev,1993,14:348-399
[56]Kenji Moriyama,Tetsuya Tagami,Takashi Akamizu,etal.Thyroid Hormone Action Is Disrupted by Bisphenol A as an Antagonist[J].Clin Endocrinology,2002,87(11):5185-5190
[57]R.Thomas Zoeller,Ruby Bansal,Colleen Parris.Bisphenol A,An environmental Contaminant that Acts as a Thyroid Hormone Receptor Antagonist In Vitro,Increases Serum Thyroxine and Alters RC3/Neurogranin Expression in the Developing Rat Brain[J].Endocrinology,2005,146(2):607-612
[58]Sakazaki H,etal.[J]Toxicol Lett,2002,133(23):221-229.
[59]Kazuma Y,etal.[J]Health Sci,2003,49(3):195-204.
[60]庄惠生,杨光.双酚A对鲤鱼急性和亚急性毒性的研究[J].环境化学,2005,24(6):682-683
[61]Jolanki R,Kanerva L,Estlander T.Occupational allergic contact dermatitis caused by epoxy diacrylate in ultraviolet-light-cured paint,and Bisphenol A in dental composite resin[J].Contact Dermatitis,1995,33(2):94-99
[62]Latendresse JR,etal.[J]Toxicol Sci,2001,62(1):140-147.
[63]Joyce U,etal.[J]Toxicol Appl Pharmacol,1996,139:437-444.
[64]Zou E,Fingerman M.[J]Ecotoxicol Environ Saf,1999,42(2):185-190.
[65]Zou E,Fingerman M.[J]Ecotoxicol Environ Saf,1997,38(3):281-285.
[66]Ruh MF,etal.[J]Endocrine,1998,9(2):207-211.
[67]Ruehlmanaa D,etal.[J]FASEBJ,1998,12(7):613-619.
[68]Nimrod AC,Benson WH.[J]Crit Rew Toxicol,1996,2(3):335-364.
[69]石峻岭,杨水莲,肖国兵,郑力行等.普通人群血清双酚A水平的测定.[J]环境与职业医学,2004,621(3):190-194
[70]肖全伟,黎源倩,张浩,等.高效液相色谱法测定大鼠血清中4-壬基酚和双酚A.[J]四川大学学报(医学版),2004,35(2):271-273
[71]王玉飞,陈衡平,陈晖.桶装饮用水中双酚A的溶出及GC/MS分析.[J]中国卫生检验杂志2003,13(5):581-582
[72]郑力行,石峻岭,周志俊.高效液相色谱法测定血清中的双酚A.[J]中华预防医学杂志2003,37(11):450-451
[73]Jin X,Jiang G,Huang G,etal.Determination of 4-tert-octylphenol,4-nonylphenol and bisphenol A in surface waters from the Haihe River in Tianjin by gas chromatography-mass spectrometry with selected ion monitoring.[J]Chemosphere.2004 Sep;56(11):1113-9
[74]Jin XL,Huang GL,Jiang GB,etal.Simultaneous determination of 4-tert-octylphenol,4-nonylphenol and bisphenol A in Guanting Reservoir using gas chromatography-mass spectrometry with selected ion monitoring.[J]J Environ Sci(China).2004;16(5):825-8
[75]吴同俊,郑力行,吴强恩等.酶水解.高效液相色谱法测定人血清中双酚A.[J]中国工业医学杂志,2006,19(2):70-74
[76]Zafra A,del Olmo M,Suarez B,etal.Gas chromatographic-mass spectrometric method for the determination of bisphenol A and its chlorinated derivatives in urban wastewater.[J]Water Res.2003 Feb;37(4):735-42
[77]堀江正一.LC/MS法测定听装饮料中的双酚A.[J]分析化学,1999,48(6).:579-587
[78]张海峰,胡建英,常红等.SPE-LC-MS法检测杭州地区饮用水水源及自来水中的双酚A.[J]环境化学E 2004.23(5):584-586
[79]Ye X,Kuklenyik Z,Needham LL,etal..Measuring environmental phenols and chlorinated organic chemicals in breast milk using automated on-line column-switching-high performance liquid chromatography-isotope dilution tandem mass spectrometry.[J]J Chromatogr B Analyt Technol Biomed Life Sci.2006 Feb 2;831(1-2):110-5
[80]Soren N.Pedersen,Christian Lindholst.Quantification of the xenoestrogens 4-tert-octylphenol and bisphenol A in water and in fish tissue based on microwave assisted extraction,solid-phase extraction and liquid chromatography-mass spectrometry.[J]Journal of Chromagraphy A,1999,864:17-24
[81]Kang JH,Kito K,Kondo F.Factors influencing the migration of bisphenol A from cans.[J]J Food Prot.2003 Aug;66(8):1444-7
[82]R.Carabias-Martinez,E.Rodrigue,etal.Determination of weakly acidic endocrine-disrupting compounds by liquid chromatography-mass spectrometry with post-column base addition.[J]J Chromatogr A.,2004,1056:131-138
[83]Basheer C,Lee HK.Analysis of endocrine disrupting alkylphenols,chlorophenols and bisphenol-A using hollow fiber-protected liquid-phase microextraction coupled with injection port-derivatization gas chromatography-mass spectrometry.[J]J Chromatogr A.2004 Nov 19;1057(1-2):163-9
[84]Arthur C L,Pawliszyn J.Solid Phase Microextraction with Thermal Desorption Using Fused Silica Optical Fibers.[J]Analytical Chemisry,1990,62:2145-2148
[85]del Olmo M,Zafra A,Suarez B,etal.Use of solid-phase microextraction followed by on-column silylation for determining chlorinated bisphenol A in human plasma by gas chromatography-mass spectrometry.[J]J Chromatogr B Analyt Technol Biomed Life Sci.2005 Mar 25;817(2):167-72
[86]Kawaguchi M,Ito R,Endo N,etal.Liquid phase microextraction with in situ derivatization for measurement of bisphenol A in river water sample by gas chromatography-mass spectrometry [J]J ChromatogrA.2006 Mar 31;1110(1-2):1-5
[87]Barker S A et al.,J.Chromatogr,1989,475(1):353-361
[88]Braunrath R,Podlipna D,Padlesak S,etal.Determination of bisphenol A in canned foods by immunoaffinity chromatography,HPLC,and fluorescence detection.[J]J.Agric.Food Chem.2005,53,8911-8917
[89]邵兵,高迎新,韩灏,基质固相分散萃取—液相色谱—质谱/质谱测定牛奶和鸡蛋中的烷基酚和双酚A.[J]环境化学,2005,24(4):483-484
[90]Lee HB,Peart TE.Determination of bisphenol A in sewage effluent and sludge by solid-phase and supercritical fluid extraction and gas chromatography/mass Spectrometry.[J]J AOAC Int.2000 Mat-Apr;83(2):290-7
[91]Kawaguchi M,Sakui N,Okanouchi N,etal.Stir bar sorptive extraction with in situ denvatization and thermal desorption-gas chromatography-mass spectrometry for measurement of phenolic xenoestrogens in human urine samples.[J]J Chromatogr B Analyt Technol Biomed Life Sci.2005 Jun 5;820(1):49-57
[92][118]Inolle K,Kawaguchi M,Funakoshi Y,etal.Size-exclusion flow extraction of bisphenol A in human urine for liquid chromatography-mass spectrometry.[J]J Chromatogr B Analyt Technol Biomed Life Sci.2003 Dec 5;798(1):17-23
[93][119]Kawaguchi M,Inoue K,Yoshimura M,etal.Trace analysis of phenolic xenoestrogens in water samples by stir bar sorptive extraction with in situ derivatization and thermal desorption-gas chromatography-mass spectrometry.[J]J Chromatogr A.2004 Jul 2;1041(1-2):19-26
[94][120]Kawaguchi M,Ito R,Endo N,etal..Liquid phase microextraction with in situ derivatization for measurement of bisphenol A in river water sample by gas chromatography-mass spectrometry.[J]J ChromatogrA.2006 Mar 31;1110(1-2):1-5
[95][121]Thomson BM,Grounds PR.Bisphenol A in canned foods in New Zealand:an exposure assessment.[J]Food Addit Contam.2005 Jan;22(1):65-72
[96]Kuklenyik Z,Ekong J,Cutchins CD,etal.Simultaneous measurement ofurinary bisphenol A and alkylphenols by automated solid-phase extractive derivatization gas chromatography/mass spectrometry.[J]Anal Chem.2003 Dec 15;75(24):6820-5
[97]周益奇,许宜平,马梅,等 柱前衍生/气相色谱-质谱法同时测定壬基酚方法研究[J]分析测试学报,2005,24(1):49-52
[98]Moeder M,Martin C,Harynuk J,etal.Identmcation ofisomeric 4-nonylphenol strucntures by gas chromatography-tandem mass spectrometry combined with cluster analysis.[J]Chromatogr A,2006,1102(1-2):245-255
[99]Smith E,etal.[J]J Environ Monit,2001,3(6):616-620
[100]Pedersen SN,etal.[J]J Chromatogra,1999,864(1):17-24
[101]Careri M,Elviri L,Mangia A.Development and validation of a memod using on-line solid-phase extraction and liquid chrOmatography with ultraviolet detection for me determination ofbisphenol A,octylphenol,and nonylphenolin ground water.[J]AOAC Int,2001,84(5):1383-1392
[102]SunY,Irie M,Kishikawa N,etal.Determination of bisphenol A in human breast milk by HPLC with column-switching and fluorescence detection.[J]Biomed Chromatogr 2004 Oct;18(8):501-7
[103]Chu S,Haffner GD,Letcher RJ.Simultaneous determination of tetrabromobisphenol A,tetrachlorobisphenol A,bisphenol A and other halogenated analogues in sediment and sludge by high performance liquid chromatography-electrospray tandem mass spectrometry.[J]J ChromatogrA.2005 Dec 2;1097(1-2):25-32
[104]Kawaguchi M,Takahashi S,Seshimo F,etal.Determination of 4-tert.-octylphenol and 4-nonylphenol in laboratory animal feed sample by stir bar sorptive extraction followed by liquid desorption and column-switching liquid chromatography-mass spectrometry with solid-phase extraction.[J]J ChromatogrA.2004 Aug 13;1046(1-2):83-8
[105]Meyer J,etal.[J]AnaI Chem,2003,75(4):922-926
[106]邵兵,韩灏一,李冬梅等.加速溶剂萃取—液相色谱、质谱/质谱法分析动物组织中的壬基酚、辛基酚和双酚A.[J]色谱,2005,23(4):362-365
[107]韩灏,邵兵,马亚鲁等.高效液相色谱法测定饮料类食品中的类雌激素.[J]色谱,2005,23(2):176-179
[108]R.Braunrath,D.Podlipna,S.Padlesak.etal.Determination of BPA in canned foods by immunoaffinity chromatography,HPLC,and fluorescence detection.[J]J.Agric.Food Chem.2005,53,8911-8917
[109]Stroheker T,etal.[J]Reprod Toxicol,2003,17(4):421-432
[110]范奇元,申立军,丁训诚等.用子宫增重试验检测壬基酚的雌激素样作用.[J]劳动医学,2000,17(4):196-197
[111]张玉敏,李海山,崔金山.采用子宫增重法检测壬基酚、双酚A雌激素样活性及其联合作用.[J]中国工业医学杂志,2006,19(5):269-272
[112]Paris F,etal.[J]Mol Cell Endofinol,2002,193(1-2):43-49.
[113]GutendorfB,etal.[J]Toxicol,2001,166(1-2):79-89.
[114]Koda T,etal.[J]Environ Toxicol Chem,2002,21(12):2536-2541.
[115]梁志坚,刘艳和,刘贵明等.塑料制品中双酚A高压液相色谱测定.[J]中国公共卫生,2005,21(9):1146-1147
[116]Kang JH.Kondo F.Bisphenol A migration from cans containing coffee and caffeine.[J]Food Addit Contain.2002 Sep;19(9):886-90
[117]Munguia-Lopez EM,Peralta E,Gonzalez-Leon A,etal.Migration of bisphenol A(BPA)from epoxy can coatings to jalapeno peppers and an acid food simulant.[J]J Agric Food Chem.2002 Dec 4;50(25):7299-302
[118]Munguia-Lopez EM,Gerardo-Lugo S,Peralta E,etal.Migration of bisphenol A(BPA)from can coatings into a fatty-food simulant and tuna fish.[J]Food Addit Contam.2005Sep;22(9):892-8
[119]Naylor,C.G.,.Proceeding of the CESIO 4th World surfurcant congress,BarcelOna,spain;European Conlmittee on surfancants and detergents;Brussels,Belgium,1996,378-391
[120]Field,JA.;Reed,R L.;Nonylphenol polyethoxy carboxylate metabolites of nonionic surfactants in US paper mill effluents,mllnicipal sewage treatment plant emuents,and river waters.Environ.Sci.Technol.1996,30:3544-3550.
[121]Department of the environment.Uses,fate and entry to the environment of nonylphenol ethoxvlates.Firlal report.Consultants in Environmental sciences limited. 1993
[122]Nakamura,Y.;J.Jpn.Soc.Water Environ.1998,21:192-196
[123]黄宏周,化学产品手册:212业表面活性剂,化学工业出版社,北京,1998
[124]Blackburn,M A.;Waldock,M J.;Concentrations of Alkylphenols in River and Estuaries in England and Wales.Water Res.1995,29:1623-1629
[125]Dachs J,Van Ry DA,Eisenreich SJ.Occurrence of estrogenic nonylphenols in the urban and coastal atmosphere of the Lower Hudson River Estuary.[J]Environ Sci Technol,1999,33:2676-2679
[126]Van Ry DA,Dachs J,Gigliotti CL,et a1.Atmospheric seasonal trends and environmental fate of alkylphenols in the Lower Hudson River Esruary.[J]Environ Sic Technol.2000,34:2410-2417
[127]27 Silvia B,Georg S,Reimer H.Development and validation of a method for determination of trace levels of alkylphenols and bisphenol A in atmospheric samples.[J]Chemosphere,2004,54:575-584
[128]Khim JS,Lee KT,Kannan K,etal.Trace orgamic contaminants in sediment and water from Ulsan Bay and its Vicinity,Korea(J)Arch EnViron Contam Toxic01,2001,40:141-150
[129]Heemken OP.Reincke H,Stachel B,et al.The occurrence of xenoe strogens in the Elbe river and the Nonh Sea(J).Chermosphere,2001,45:245-259
[130]梁增辉,何世华,孙成均,等.引起青蛙畸形的环境内分泌干扰物的初步研究[J].环境与健康杂志.2002,19(6):419-421
[131]Blackbum MA,WaldockMJ.Concentration sofalkyl phenolsin rivers and estaries in England and Wales.[J].Wat Res,1995,29(7):1623-1629.
[132]Ahel M,Giger W,SchaffnerC.behavipuro falkylphenol polyethoxylate surfactants in the aquaticenvironment II.Occurrencea and trans formation in the rivers[J]..Wat Res,,1994,28(5):1143-1152.
[133]Naylor CG,Mieure JP,Adams wJ,etal.Alkylphenol ethoxylates in the environment[J]J Am OilChem Soc,1992,69(7):695-703.
[134]胡建英,等.[J].净水技术,2001,20(3):36.
[135]Ekelund RA,Bergma A,Granmo A,etal.Bioaccumulation of 4-Nonylphenol in marine animals.[J]Environ Pollution,1990,64(2):107 120.
[136]Jeannot R,etal.[J]J Chromatogr A,2002,974(1-2):143-159
[137]Koh CH,etal.[J]Environ Toxicol Chem,2002,21(9):1796-1803
[138]Petrick G,Schulz-Bull DE,Duinker JCZ-Analyses of polychlorinated-biphenyls and organic contaminants in drinking-wateL[J]Wasser-Acta Hydroc.1992,25:115-121
[139]Kuch HM,etal.[J]Environ Sci Technol,2001,35(15):3201-3206
[140]Li Z,Li D,Oh JR,etal.Seasonal and spatial distribution of nonylphenol in Shihwa Lake,Korea.[J]Chemosphere.2004 Aug;56(6):611-8
[141]Isobe T,Takada H,Kanai M,etal.Distriution of Polycyclic Aromatic Hydrocarbons (PAHs)and phenolic endocrine disrupting chemicals in South and Southeast Asian rnussels.[J]Environ Monit Assess.2007,17
[142]范奇元,金泰,将学之,等.我国部分地区环境中壬基酚的检测.[J]中国公共卫生,2002,18(11):1372-1373
[143]rsuda T,etal.[J]J Chrimatogr B Biomed Sci Appl,1999,723(1-2):273-279
144 Ferrata F,etal.[J]Environ Sci Technol,2001,35(15):3109-3112
145 Schonfelder G,Wittfoht W,Hopp H,etal.Parent bisphenol A accumulation in me human maternal fetal placental unit[J].Environ Health perspect,2002,110:A 703 A707
146Off.J.Eur.Communities 2004,L71(19/EC),8-21
147 European commission,Scientific Commitree on food,Opinion of the Scientific Committee on Food on Bisphenol A,SCF/CS/PM3936 Final 3 May 2002,EC,Brussel,Belgium;see also (http://www.europa.eu.in/comm./food/fs/sc/scf/index.en.html)
148 Thomson BM,Grounds PR.Bisphenol A in canned foods in new Zealand:an exposure assessment.[J]Food Addit Contam.2005,22(1):65-72
149 Guenther K.,Heinke V.,Thiele B.el al.Endocrine disrupting nonylphenols are ubiquitous in food.[J]Environ.Sci.Technol.2002,36:1676-1680
150 Petrovic M.Barcelo D.Determination of phenolic xenoestrogens in environmental samples by liquid chromatography with mass spectrometric detection.[J]J AOAC Int.2001Jul-Aug84(4);1074-85
1 R.Carabias-Martinez,E.Rodrigue,etal,Determination of weakly acidic endocrine-disrupting compounds by liquid chromatography-mass spectrometry with post-column base addition.[J]J ChromatogrA.,2004.1056:131-138
[1]del Olmo M,Zafra A,Suarez B,etal.Use of solid-phase microextraction followed by On-column silylation for determining chlorinated bisphenol A in human plasma by gas chromatography-mass spectrometry.[J]J Chromatogr B Analyt Technol Biomed Life Sci.2005 Mar 25;817(2):167-72
[3]石峻岭,杨水莲,肖国兵,郑力行等.普通人群血清双酚A水平的测定.[J]环境与职业医学,2004,621(3):190-194
[4]Inoue K,Kawaguchi M,Funakoshi Y,etal.Size-exclusion flow extraction of bisphenol A in human urine for liquid chromatography-mass spectrometry.[J]J Chromatogr B Analyt Technol Biomed Life Sci.2003 Dec 5;798(1):17-23
[5]Ye X,Kuklenyik Z,Needham LL,etal..Measuring environmental phenols and chlorinated organic chemicals in breast milk using automated on-line column-switching-high performance liquid chromatography-isotope dilution tandem mass spectrometry.[J]J Chromatogr B Analyt Technol Biomed Life Sci.2006 Feb 2;831(1-2):110-5
[1]Consolidated TEXT produced by the CONSLEG system of the Office for Official Publications of the European Communities:1982L0711-01/09/1997
[1]Ekelund RA,Bergma A,Granmo A,etal.Bioaccumulation of 4-Nonylphenol in marine animals.[J]Environ Pollution,1990,64(2):107 120.
[2]Mountfort KA,Kelly J,Jickells SM,etal.Investigations into the potential degradation of polycarbonate baby bottles during sterilization with consequent release of bisphernol A(J).Food Addit Contam,1997,14:737-740
[3]Nakagomi M,etal.[J]Teratog Carcinog Mutagen,2001,21(6):453-462.
[4]NTP.Carcinogenesis bioassay of bisphenol A(CAS No.80-05-7)in F344 rats and B6C3F1mice(feed study)[J].National Toxicology Program,Technical Report Series,1982,215:1-116
[5]Lois A,Haighton,Jason J.An Evaluation of the Possible Carcinogenicity of Bisphenol A to Humans[J].Regulatory Toxicology and Pharmacology,2002,35(2):238-254
[6]Naylor CG,Mieure JP,Adams WJ,etal.Alkylphenol ethoxylates in the environment[J].J Am Oil Chem Soc,1992,69(7):695-703.
[7]建英,等.[J].净水技术,2001,20(3):36.