劉娜，金小偉，王業(yè)耀,，呂怡兵，楊琦

1. 中國(guó)地質(zhì)大學(xué)(北京)水資源與環(huán)境學(xué)院，北京 100083 2. 中國(guó)環(huán)境監(jiān)測(cè)總站，北京 100012

我國(guó)地表水中藥物與個(gè)人護(hù)理品污染現(xiàn)狀及其繁殖毒性篩查

劉娜1，金小偉2,*，王業(yè)耀1,2，呂怡兵2，楊琦1

1. 中國(guó)地質(zhì)大學(xué)(北京)水資源與環(huán)境學(xué)院，北京 100083 2. 中國(guó)環(huán)境監(jiān)測(cè)總站，北京 100012

根據(jù)文獻(xiàn)報(bào)道，我國(guó)地表水中已檢出至少144種藥物及個(gè)人護(hù)理用品(pharmaceuticals and personal care products, PPCPs)，包括抗生素、激素、其他藥物、個(gè)人護(hù)理品(personal care products, PCPs) 4大類，其中檢出濃度最高的達(dá)到了μg·L-1量級(jí)，在長(zhǎng)期的污染下有可能對(duì)水生生物產(chǎn)生內(nèi)分泌干擾效應(yīng)或繁殖毒性，進(jìn)而影響到整個(gè)水生生物種群的繁衍變化。因此，有必要根據(jù)我國(guó)地表水中PPCPs的污染水平，篩查出具有潛在生態(tài)風(fēng)險(xiǎn)的PPCPs。由于目前缺乏針對(duì)PPCPs類污染物的篩選體系，以國(guó)內(nèi)外優(yōu)先控制污染物篩選體系為基礎(chǔ)，借鑒基于風(fēng)險(xiǎn)的歐洲獸藥分級(jí)方法，利用風(fēng)險(xiǎn)指數(shù)(risk index, RI)，篩選得出目前我國(guó)的地表水中有16種具有繁殖毒性的PPCPs的RI>1，包括1種抗生素，5種激素類藥物，3種其他藥物和7種PCPs，其中乙炔雌二醇(ethinylestradiol, EE2)的RI最高(115 730)，其次是壬基酚(nonylphenol, NP)(1 796)、鄰苯二甲酸二丁酯(dibutyl phthalate, DBP) (255.31)，對(duì)水生態(tài)環(huán)境有較高的風(fēng)險(xiǎn)的PPCPs需進(jìn)一步進(jìn)行較高層次的風(fēng)險(xiǎn)評(píng)價(jià)。

藥物和個(gè)人護(hù)理用品；篩查方法；繁殖毒性；地表水

藥物與個(gè)人護(hù)理品(pharmaceuticals and personal care products, PPCPs)的概念最早由Christian G. Daughton于1999年提出，其中藥物主要包括人類用藥和獸藥，如β-受體阻滯藥、消炎劑、脂肪調(diào)節(jié)劑、抗生素、止痛藥、鎮(zhèn)靜劑、抗癲癇藥、顯影劑、降壓藥、避孕藥等，個(gè)人護(hù)理品(personal care products, PCPs)主要為香料、化妝品、遮光劑、染發(fā)劑、發(fā)膠、香皂、洗發(fā)水等[1-3]。據(jù)統(tǒng)計(jì)，全世界生產(chǎn)和使用的各類藥物己達(dá)50 000余種，人用藥物年消費(fèi)量約為3 000萬(wàn)t左右，而用作獸藥及添加劑的藥品用量則更為龐大，全球每年僅抗生素類藥物一項(xiàng)的使用量就超過(guò)200萬(wàn)t[4]。我國(guó)是藥物生產(chǎn)和使用大國(guó)之一，藥物產(chǎn)量占世界總產(chǎn)量的20%以上，生產(chǎn)藥物活性成分1 500多種[5]。同時(shí)，我國(guó)PCPs消耗量世界排名第三，占全球消耗量的6.5%，僅次于美國(guó)(19.1%)和日本(9.4%)[6]。由于大量的生產(chǎn)和使用，PPCPs源源不斷地進(jìn)入地表水環(huán)境，形成“假性持續(xù)性”現(xiàn)象[7-9]，其在環(huán)境中的存在已成為一個(gè)社會(huì)問(wèn)題。PPCPs具有較強(qiáng)的生物活性，并且在一般環(huán)境條件下具有一定的持久性和生物累積性等特點(diǎn)，盡管環(huán)境殘留水平較低，但長(zhǎng)期暴露依然會(huì)給人類健康和生態(tài)環(huán)境帶來(lái)潛在風(fēng)險(xiǎn)[10-11]。因此，本研究在充分調(diào)研我國(guó)地表水中PPCPs污染水平的基礎(chǔ)上，綜述國(guó)內(nèi)外優(yōu)先控制污染物篩選體系研究現(xiàn)狀，介紹了篩選體系框架，以及篩選過(guò)程中評(píng)價(jià)因子的確定和計(jì)算方法。并借鑒基于風(fēng)險(xiǎn)的歐洲獸藥分級(jí)方法，利用風(fēng)險(xiǎn)指數(shù)(risk index, RI)，篩選出具有繁殖毒性的PPCPs及其潛在生態(tài)風(fēng)險(xiǎn)，以期為PPCPs管理提供理論依據(jù)及科學(xué)基礎(chǔ)。

1　我國(guó)地表水PPCPs污染水平(Contaminate levels of PPCPs in Chinese surface waters)

據(jù)文獻(xiàn)報(bào)道，目前在我國(guó)河流、湖泊和近岸海域等天然水環(huán)境中檢出的PPCPs有144種，包括70種抗生素，33種激素類藥物，20種其他類藥物和21種PCPs，檢出濃度為ng·L-1～μg·L-1水平。分析最近10年文獻(xiàn)報(bào)道中各類PPCPs最高檢出濃度的分布區(qū)間(見(jiàn)圖1)，抗生素類藥物濃度主要分布在10～100 ng·L-1(占44%)和100～1 000 ng·L-1(占26%)；激素類藥物檢出濃度最低，42%分布在0～10 ng·L-1之間，44%分布在10～100 ng·L-1；其他藥物的最大檢出濃度均大于20 ng·L-1，主要分布在100～1 000 ng·L-1水平區(qū)間(占50%)；PCPs的檢出濃度最高，50%的PCPs檢出濃度大于1 000 ng·L-1。

圖1　各類PPCPs污染水平分析Fig. 1　Contamination levels of PPCPs in Chinese surface waters

(1)抗生素類

在4類PPCPs中，抗生素的檢出頻率與濃度最高，6種抗生素的檢出頻率大于60%[12]，包括磺胺甲噁唑(sulfadiazine, SD)、磺胺嘧啶(sulfamerazine, SM1)、諾氟沙星(norfloxacin, NFX)、氧氟沙星(ofloxacin, OFX)、紅霉素(erythromycin, ERY)和羅紅霉素(roxithromycin, ROX)；11種抗生素的檢出濃度達(dá)到μg·L-1水平(見(jiàn)表1)，占總檢出種類的16%，主要分布在貴陽(yáng)南明河、渤海灣-海河流域和珠江流域。貴陽(yáng)南明河檢出濃度最高，氯霉素(chloramphenicol, CAP)、四環(huán)素(tetracycline, TC)和土霉素(oxytetracycline, OTC)的檢出濃度均>3 μg·L-1，其中CAP高達(dá)19 μg·L-1[13]，遠(yuǎn)遠(yuǎn)高于珠江266 ng·L-1[14]；其次是渤海灣-海河流域，檢出濃度最高的是NFX，為6.8 μg·L-1[15]；珠江流域的抗生素檢出濃度較低，ERY最高為1.54 μg·L-1[18]。

(2)激素類

我國(guó)地表水中激素類藥物主要有雌激素、雄激素、孕激素和糖皮質(zhì)激素4類，目前相關(guān)報(bào)道主要集中在乙炔雌二醇(ethinylestradiol, EE2)、雌酮(estrone, E1)、雌二醇(estradiol, E2)、雌三醇(estriol, E3)、己烯雌酚(diethylstilbestrol, DES)、己烷雌酚(hexoestrol, HES)等6種雌激素。分析檢出濃度較高的3個(gè)地表水水體，大連排污河的污染最嚴(yán)重，6種雌激素均有檢出，且濃度>26.9 ng·L-1，其中EE2的濃度高達(dá)3 471.9 ng·L-1[19]；其次是九龍江，在檢出的E1、E2、E3和DES等4種雌激素中，E1的濃度最大(321.02 ng·L-1)[20]，DES濃度最小(24.9 ng·L-1)[19]；Zhou等[21]在膠州灣檢測(cè)了EE2、E1、E2和E3，濃度分別為94 ng·L-1、180 ng·L-1、134 ng·L-1、24 ng·L-1，污染程度相對(duì)較小。

表1我國(guó)地表水中主要PPCPs的最大濃度及分布特征

Table 1The highest concentration and distribution characteristics of main PPCPs in Chinese surface waters

分類Classification化學(xué)品號(hào)CAS.化學(xué)品名稱Chemical濃度/(ng·L-1)Concentration/(ng·L-1)流域Watershed參考文獻(xiàn)Ref.抗生素Antibiotics56-75-7氯霉素Chloramphenicol,CAP19000貴陽(yáng)南明河Nanmingriver,Guiyang[13]60-54-8四環(huán)素Tetracycline,TC6800貴陽(yáng)南明河Nanmingriver,Guiyang[13]70458-96-7諾氟沙星Norfloxacin,NFX6800渤海灣Bohaibay[15]82419-36-1氧氟沙星Ofloxacin,OFX5100渤海灣Bohaibay[15]80214-83-1羅紅霉素Roxithromycin,ROX3700海河Haiheriver[16]79-57-2土霉素Oxytetracycline,OTC3000貴陽(yáng)南明河Nanmingriver,Guiyang[13]23893-13-2脫水紅霉素Erythromycin-H2O, ERY-H2O1900維多利亞港VictoriaHarbour[17]114-07-8紅霉素Erythromycin,ERY1540石井河Shijingriver[18]57-68-1磺胺二甲基嘧啶Sulfamethazine,SM21390珠江Pearlriver[16]127-79-7磺胺嘧啶Sulfamerazine,SM11080石井河Shijingriver[14]57-62-5金霉素Chlorotetracycline,CTC1036九龍江Jiulongjiangriver[16]激素Hormones57-63-6乙炔雌二醇Ethynylestradiol,EE23471.9大連排污河Drainageriver,Dalian[19]53-16-7雌酮Estrone,E1321.02九龍江Jiulongjiangriver[20]50-28-2雌二醇17β-estradiol,E2134膠州灣Kiaochowbay[21]84-16-2己烷雌酚Hexoestrolum,HES103.7大連排污河Drainageriver,Dalian[19]50-27-1雌三醇Estriol,E394膠州灣Kiaochowbay[21]56-53-1己烯雌酚Diethylstilbestrol,DES28.2大連排污河Drainageriver,Dalian[19]其他藥物Otherdrugs69-72-7水楊酸Salicylicacid,SALA14736珠江Pearlriver[24]73334-07-3碘普羅胺Iopromide,IOP1439珠江Pearlriver[25]58560-75-1布洛芬Ibuprofen,IBU1417珠江Pearlriver[26]298-46-4卡馬西平Carbamazepine,CMP1090長(zhǎng)江Yangtzeriver[27]53-86-1吲哚美辛Indomethacin,IND979長(zhǎng)江Yangtzeriver[28]15307-86-5雙氯芬酸Diclofenac,DIC843長(zhǎng)江Yangtzeriver[29]58-08-2咖啡因Caffeine,CAF824黃浦江Huangpuriver[29]644-62-2甲氯芬那酸Meclofenamicacid,MECA679長(zhǎng)江Yangtzeriver[28]22204-53-1萘普生Naproxen,NAP328珠江Pearlriver[26]882-09-7氯貝酸Clofibricacid,CLOA248珠江Pearlriver[26]

對(duì)于另外3類激素，侯麗萍等[22]檢測(cè)了廣東四會(huì)鄧村河的10種雄激素和孕激素，結(jié)果顯示，1,4-雄烯二酮、反式雄酮、雄酮的最大濃度分別為30.46 ng·L-1、18.93 ng·L-1、12.05 ng·L-1，其他均小于10 ng·L-1；譚麗超等[23]檢測(cè)了南京市地表水中7種糖皮質(zhì)類激素，檢出濃度為2.88～60.76 ng·L-1。

(3) 其他藥物類

我國(guó)地表水中檢出的其他藥物主要是消炎止痛藥、抗驚厥藥、降壓藥和降血脂藥。在檢出濃度最高的10種藥物中，報(bào)道最多的是布洛芬(ibuprofen, IBU)、卡馬西平(carbamazepine, CMP)、雙氯芬酸(diclofenac, DIC)、萘普生(naproxen, NAP)和氯貝酸(clofibric acid, CLOA)，檢出頻率為30%～60%[12]。分析其他類藥物的地域分布，珠江和長(zhǎng)江流域(包括其支流黃浦江)污染最嚴(yán)重，分別有5種藥物檢出，但珠江的污染程度明顯大于長(zhǎng)江。其中水楊酸(SALA)的檢出濃度最高(14.736 μ g·L-1)[24]，遠(yuǎn)遠(yuǎn)高于排名第二的碘普羅胺(IOP)(1.439 μg·L-1)[25]。

(4) PCPs類

PCPs中報(bào)道最多的是具有雌激素效應(yīng)的壬基酚(nonylphenol, NP)和鄰苯二甲酸酯類(phthalic acid esters, PAEs)，其次是三氯生(triclosan, TCS)和三氯卡班(triclocarban, TCC)。分析污染水平達(dá)到μg·L-1的10種PCPs(見(jiàn)表1)，有6種屬于PAEs，其中鄰苯二甲酸二丁酯(dibutyl phthalate, DBP)的檢出濃度最高，為5.6168 μg·L-1[30]，鄰苯二甲酸二(2-乙基己基)酯(di 2-ethylhexyl phthalate, DEHP)、鄰苯二甲酸二甲酯(dimethyl phthalate, DMP)、鄰苯二甲酸二乙酯(diethyl phthalate, DEP)和鄰苯二甲酸二正辛酯(di-n-octyl phthalate, DOP)等4種PAEs的檢出濃度均大于100 μg·L-1；NP在武漢東湖的檢出濃度為179.6 μg·L-1[31]，遠(yuǎn)遠(yuǎn)高于其他地區(qū)的檢出水平(九龍江1.688 μg·L-1[20])；對(duì)羥基苯甲酸丙酯(propylparaben, PP)、對(duì)羥基苯甲酸甲酯(methylparaben, MP)和TCS在珠江的檢出濃度最高。此外，TCC在珠江支流石井河檢出濃度最高(88 ng·L-1[18])，麝香類化學(xué)品在海河的檢出濃度最高，為26.7～34.6 ng·L-1[33]。

2　PPCPs篩選體系研究現(xiàn)狀(Research status on screening system of PPCPs)

由于水環(huán)境中的PPCPs種類繁多，各種PPCPs的理化性質(zhì)及分子結(jié)構(gòu)均不相同，在水環(huán)境中的濃度分布及遷移轉(zhuǎn)化過(guò)程也有很大差別，導(dǎo)致其生態(tài)風(fēng)險(xiǎn)也有所差異。為了正確評(píng)估PPCPs對(duì)水生態(tài)安全性的影響，首先需要建立一套有毒有害PPCPs篩查方法。

2.1篩選體系概況

近年來(lái)，歐美國(guó)家發(fā)展了一些針對(duì)環(huán)境中潛在有毒有害的化學(xué)物質(zhì)以及獸藥的篩選方法[36]。Bu等[37]分析總結(jié)了最近20年國(guó)外各國(guó)政府及科研組研發(fā)的27種優(yōu)先污染物篩選體系，根據(jù)使用目的，將篩選體系分為3類：第一類，通過(guò)篩選體系得到優(yōu)先控制污染物名單，作為政府管理依據(jù)，如Hansen等[38]開(kāi)發(fā)的EURAM；第二類，設(shè)定篩選條件，對(duì)目標(biāo)污染物進(jìn)行分級(jí)或排名，為開(kāi)展下一步工作奠定基礎(chǔ)，如Kool等[39]開(kāi)發(fā)的基于環(huán)境風(fēng)險(xiǎn)的歐洲獸藥分級(jí)方法和Mitchell等[40]開(kāi)發(fā)的用于美國(guó)五大湖的污染物篩查的SCRAM；第三類，直接用來(lái)評(píng)價(jià)化學(xué)品對(duì)環(huán)境的影響或用于指導(dǎo)生命周期評(píng)價(jià)，如美國(guó)環(huán)保局(US EPA)開(kāi)發(fā)的RSEI。

由于評(píng)價(jià)目的和篩選標(biāo)準(zhǔn)不同，各篩選體系之間區(qū)別較大，但篩選體系框架大致相同，主要分為4個(gè)步驟[37]：①根據(jù)商業(yè)生產(chǎn)和使用信息確定待篩選的化學(xué)品清單集；②確定測(cè)試終點(diǎn)和評(píng)價(jià)因子；③賦值計(jì)算；④根據(jù)計(jì)算結(jié)果對(duì)目標(biāo)污染物進(jìn)行排序或分級(jí)，取分值或級(jí)別較高的作為優(yōu)先控制污染物。其中最關(guān)鍵的是評(píng)價(jià)因子的選擇和賦值計(jì)算。

2.2篩選體系關(guān)鍵技術(shù)

(1)評(píng)價(jià)因子

優(yōu)先控制污染物篩選主要考慮化學(xué)品本身的毒性和環(huán)境暴露濃度，此外還要根據(jù)需要考慮其持久存在性和生物累積性，如半衰期(T1/2)、自然降解能力和生物富集系數(shù)(bioconcentration factor, BCF)。

毒性數(shù)據(jù)一般來(lái)自實(shí)驗(yàn)室測(cè)定和數(shù)據(jù)庫(kù)查詢，根據(jù)“可靠性”和“相關(guān)性”原則進(jìn)行選擇。傳統(tǒng)的生物毒性測(cè)試終點(diǎn)包括生存、生長(zhǎng)和繁殖等，用半致死濃度(median lethal concentration, LC50)、半效應(yīng)濃度(median effectl concentration, EC50)、最低觀察效應(yīng)濃度(lowest observed effect concentration, LOEC)和無(wú)觀察效應(yīng)濃度(no observed effect concentration, NOEC)等評(píng)價(jià)化學(xué)品對(duì)生物體暴露的危害。根據(jù)試驗(yàn)暴露時(shí)間，分為急性毒性和慢性毒性，用急性毒性的數(shù)據(jù)來(lái)評(píng)價(jià)短期瞬時(shí)暴露效應(yīng)，用慢性毒性數(shù)據(jù)評(píng)價(jià)長(zhǎng)期持續(xù)暴露效應(yīng)，如果慢性毒性數(shù)據(jù)缺乏也可以用急性毒性數(shù)據(jù)除以一個(gè)安全因子產(chǎn)生慢性基準(zhǔn)值。由于急性毒性試驗(yàn)周期短、成本低，目前關(guān)于PPCPs對(duì)區(qū)域水生態(tài)環(huán)境效應(yīng)的報(bào)道多集中于水生生物的急性毒性[41-42]。

非傳統(tǒng)的測(cè)試終點(diǎn)包括內(nèi)分泌干擾、酶活性的誘導(dǎo)/抑制效應(yīng)、應(yīng)激蛋白誘導(dǎo)效應(yīng)，以及DNA和RNA水平的變化等。由于傳統(tǒng)的毒性測(cè)試方法耗時(shí)長(zhǎng)、花費(fèi)巨大，且因暴露劑量差異和動(dòng)物種屬差異可能導(dǎo)致較大誤差，近年來(lái)國(guó)外將這些新的毒性測(cè)試方法用于化學(xué)品篩選，如高通量篩選技術(shù)(HTS)和有害結(jié)局路徑(AOP)[43-44]。HTS是以分子水平和細(xì)胞水平的實(shí)驗(yàn)方法為基礎(chǔ)建立的藥物篩選技術(shù)體系，可以在同一時(shí)間內(nèi)對(duì)數(shù)以千、萬(wàn)計(jì)的樣品進(jìn)行檢測(cè)[43]；AOP是Ankley等[44]提出的一個(gè)概念框架，用以描述一個(gè)分子起始事件(MIE)與生物不同組織結(jié)構(gòu)層次(細(xì)胞、器官、機(jī)體、群體)出現(xiàn)的毒性效應(yīng)之間的相互聯(lián)系，從而進(jìn)行危害度評(píng)定[45-46]。

環(huán)境暴露指污染物在環(huán)境中的濃度或某一特定受體的暴露劑量[47]，一般用環(huán)境暴露濃度(environmental exposure concentration, EEC)來(lái)表示。在污染物篩選過(guò)程中，環(huán)境暴露濃度優(yōu)先使用實(shí)測(cè)數(shù)據(jù)，當(dāng)缺乏實(shí)測(cè)數(shù)據(jù)時(shí)，使用假設(shè)估算或模型預(yù)測(cè)的方法計(jì)算環(huán)境預(yù)測(cè)濃度(predicted environmental concentration, PEC)。PEC一般根據(jù)藥物的產(chǎn)量、排泄率和污水廠中藥物去除率進(jìn)行估算[48]，該方法簡(jiǎn)單易行，但準(zhǔn)確度較低。實(shí)測(cè)數(shù)據(jù)準(zhǔn)確度高，更接近實(shí)際狀況，缺點(diǎn)是檢測(cè)費(fèi)用高，而且有些情況下無(wú)法進(jìn)行實(shí)測(cè)。隨著檢測(cè)技術(shù)的提高，實(shí)測(cè)數(shù)據(jù)的獲取越來(lái)越容易，例如，以多殘留檢測(cè)方法為基礎(chǔ)，Bruchet等[49]建立了內(nèi)分泌干擾物和PPCPs篩選方法，鐘文玨等[50]建立了酚類化合物篩選方法。

(2) 計(jì)算方法

篩選體系的計(jì)算方法主要有疊置指數(shù)法和商值法，此外還有根據(jù)數(shù)學(xué)模型開(kāi)發(fā)的篩選軟件，如RSEI[37]。

疊置指數(shù)法首先根據(jù)評(píng)價(jià)因子的數(shù)據(jù)范圍確定等級(jí)，對(duì)實(shí)際數(shù)據(jù)進(jìn)行分級(jí)或賦分；然后根據(jù)評(píng)價(jià)因子的重要性確定其權(quán)重，最重要的因子指定最大的權(quán)；最后計(jì)算總分，總分越大風(fēng)險(xiǎn)越大。目前，各篩選體系尚未對(duì)評(píng)價(jià)因子形成統(tǒng)一的分級(jí)方式和賦值權(quán)重。例如，對(duì)于BCF的分級(jí)方式，SCRAM根據(jù)BCF的大小進(jìn)行1～5分賦分[40]，RICH將BCF分為高(≥5 000)、中(100～5 000)、低(<100)3個(gè)等級(jí)[51]；對(duì)于評(píng)價(jià)因子的權(quán)重，SCRAM將所有評(píng)價(jià)因子的分?jǐn)?shù)直接相加，得到綜合分?jǐn)?shù)[52-55]；王朋華等[48]認(rèn)為藥物持久存在性( SP)和藥物毒性( SH)是較重要的因子，將其權(quán)重系數(shù)設(shè)為4，而藥物預(yù)測(cè)含量( SC)的權(quán)重系數(shù)設(shè)為2，總分 S = 2 SC+ 4 SP+ 4 SH。

商值法又稱比率法，是使用最普遍、最廣泛的風(fēng)險(xiǎn)表征方法。計(jì)算方法是將EEC(或PEC)與毒性指標(biāo)值相比較，商值在某一數(shù)值范圍內(nèi)為有風(fēng)險(xiǎn)，小于該數(shù)值則為無(wú)風(fēng)險(xiǎn)。歐洲獸藥分級(jí)方法將PEC與最低效應(yīng)劑量(TDlow)相比，計(jì)算風(fēng)險(xiǎn)指數(shù)RI，然后把233種獸藥的風(fēng)險(xiǎn)分為高(RI>250)、中(50～250)、低(RI≤50)3個(gè)等級(jí)[39]；Victoria等[56]根據(jù)PEC與EC50的對(duì)比，從65種抗癌藥物中篩選出15種比值大于1的優(yōu)先控制藥物。

3　繁殖毒性PPCPs篩查(Screening of PPCPs with reproductive toxicity)

由于PPCPs具有較強(qiáng)的生物活性，部分PPCPs不僅對(duì)水生生物造成個(gè)體死亡，在低劑量長(zhǎng)期污染下還有可能對(duì)其產(chǎn)生內(nèi)分泌干擾效應(yīng)和繁殖毒性效應(yīng)，進(jìn)而影響到整個(gè)水生生物種群的繁衍及變化[57-61]。美國(guó)加州政府環(huán)境健康危害評(píng)估委員會(huì)制定的安全飲用水和毒性強(qiáng)制執(zhí)行法案(第65號(hào)提案)2014年公布的910種致癌或繁殖毒性化學(xué)品清單中，有303種具有繁殖毒性，其中65%以上是PPCPs。研究表明，人工合成雌激素在濃度僅為0.2 ng·L-1的低劑量下就會(huì)干擾魚(yú)類正常的內(nèi)分泌，并引起雄性魚(yú)的卵黃蛋白原(vitellogenin, VTG)增加，出現(xiàn)明顯的雌性化[58]；多環(huán)麝香對(duì)河蚌的生長(zhǎng)和繁殖具有一定程度的抑制作用，并且還可通過(guò)江豚胎盤(pán)轉(zhuǎn)移至胎兒體內(nèi)[59, 62]；環(huán)境激素藥物來(lái)曲唑、它莫昔芬在低劑量下就能夠?qū)η圜汈~(yú)的繁殖和早期發(fā)育產(chǎn)生明顯的影響[60-61]。Jin等[62]比較水生生物不同測(cè)試終點(diǎn)，包括生存、生長(zhǎng)、生物化學(xué)和分子生物學(xué)、繁殖對(duì)NP的敏感性差異，結(jié)果表明，基于繁殖損傷的結(jié)果最為敏感，推導(dǎo)的預(yù)測(cè)無(wú)觀察效應(yīng)濃度PNEC值最低(0.12 μg·L-1)。因此，以繁殖毒性數(shù)據(jù)為基礎(chǔ)進(jìn)行篩選，將有助于進(jìn)一步研究PPCPs對(duì)水生生物的繁殖損傷以及種群影響，為此類污染物的風(fēng)險(xiǎn)評(píng)估提供科學(xué)依據(jù)。

3.1篩查方法

根據(jù)是否考慮環(huán)境暴露濃度，篩選體系分為基于風(fēng)險(xiǎn)的(risk-based)篩選體系和基于危害性的(hazard-based)篩選體系。環(huán)境風(fēng)險(xiǎn)是污染物毒性和環(huán)境暴露的綜合作用結(jié)果，因此，繁殖毒性PPCPs篩選使用基于風(fēng)險(xiǎn)的篩選體系。由于PPCPs的BCF不大，除了布洛芬(14 000～49 000)、安定(1～64 700)和萘普生(500～2 300)，其余均小于2 000[64-66]，根據(jù)歐盟REACH法規(guī)對(duì)具有持久性、生物蓄積性和毒性的物質(zhì)(PBTs)的鑒別判定標(biāo)準(zhǔn)[67]，不屬于持久性污染物。因此，繁殖毒性PPCPs初步篩選可以借鑒基于風(fēng)險(xiǎn)的歐洲獸藥分級(jí)方法，以RI為依據(jù)對(duì)我國(guó)地表水檢出的PPCPs進(jìn)行篩查，不考慮生物累積性和環(huán)境持久性等評(píng)價(jià)因子。

3.2受試物種

由于不同類群生物對(duì)不同化學(xué)物的毒性敏感性存在很大的差異，因此受試物種的選擇非常重要。關(guān)于PPCPs對(duì)水生生物毒性的報(bào)道很多，為了準(zhǔn)確評(píng)價(jià)PPCPs對(duì)整個(gè)水生生態(tài)系統(tǒng)的影響，應(yīng)針對(duì)不同種類的PPCPs選擇最敏感生物類群。研究發(fā)現(xiàn)，對(duì)于抗生素類藥物，藻類最敏感，其次是大型溞、魚(yú)類[68]；對(duì)于激素類藥物，魚(yú)類比無(wú)脊椎動(dòng)物更為敏感[69]。

為了使篩查結(jié)果具有可比性，同類PPCPs盡可能選擇同一敏感物種[70]。例如，當(dāng)魚(yú)類為最敏感物種時(shí)，選擇國(guó)際通用模式魚(yú)類中的青鳉魚(yú)作為受試物種，該種魚(yú)已經(jīng)被OECD認(rèn)定為評(píng)價(jià)內(nèi)分泌干擾類化合物的標(biāo)準(zhǔn)受試物種[71]，具有非常豐富的毒性數(shù)據(jù)庫(kù)，可以保證數(shù)據(jù)的可靠性。當(dāng)缺乏該受試物種毒性數(shù)據(jù)時(shí)，使用同一生物類群的物種，比如用斑馬魚(yú)或虹鱒魚(yú)替代青鳉魚(yú)。

3.3測(cè)試指標(biāo)

傳統(tǒng)的繁殖毒性評(píng)價(jià)指標(biāo)有多代效應(yīng)、受精率、產(chǎn)卵量、孵化率和子代畸形率。另外，性腺指數(shù)(gonadosomatic index, GSI)和VTG水平也常作為生物標(biāo)記物來(lái)評(píng)估污染物對(duì)魚(yú)類繁殖系統(tǒng)的潛在危害[72]，但是對(duì)于這些標(biāo)記物的使用需要防止假陰性現(xiàn)象[73](機(jī)能響應(yīng)與生物標(biāo)記物響應(yīng)不相關(guān))或假陽(yáng)性現(xiàn)象[74](生物標(biāo)記物響應(yīng)未伴隨相應(yīng)的機(jī)能響應(yīng))的出現(xiàn)。Alistair等[75]提出的20個(gè)關(guān)于PPCPs管理需要優(yōu)先研究的重要問(wèn)題之一，就是如何把組織和分子水平的毒性效應(yīng)轉(zhuǎn)化成生存、生長(zhǎng)和繁殖等傳統(tǒng)生物毒性測(cè)試終點(diǎn)。由于篩選水平的評(píng)價(jià)只是對(duì)風(fēng)險(xiǎn)進(jìn)行比較粗略的估計(jì)，可以忽略各評(píng)價(jià)指標(biāo)之間的區(qū)別，在US EPA的ECOTOX數(shù)據(jù)庫(kù)中選擇敏感物種長(zhǎng)時(shí)間暴露條件下繁殖類指標(biāo)的NOEC作為評(píng)價(jià)終點(diǎn)[70,75]，當(dāng)未搜索到NOEC時(shí)，用LOEC來(lái)替代。

表2PPCPs繁殖毒性篩查結(jié)果

Table 2Screening results and risk index of PPCPs with reproductive toxicity

化學(xué)品號(hào)CAS.No.化學(xué)品名稱Chemical環(huán)境濃度/(ng·L-1)EEC/(ng·L-1)受試物種Testspecies測(cè)試指標(biāo)Measurement評(píng)估終點(diǎn)Endpoint濃度/(ng·L-1)Concentration/(ng·L-1)暴露時(shí)間/dDuration/dRI參考文獻(xiàn)Ref.57-63-6乙炔雌二醇Ethynylestradiol,EE23471.9[19]青鳉魚(yú)Oryziaslatipes雌性化FemaleLOEC0.03100115730[77]9016-45-9壬基酚Nonylphenol,NP179600[31]青鳉魚(yú)Oryziaslatipes卵黃蛋白原VTGLOEC100200～2301796[78]84-74-2鄰苯二甲酸二丁酯Dibutylphthalate,DBP5616800[30]九孔鮑Haliotisdiversicolorsupertexta胚胎發(fā)育embryoNOEC220004255.31[79]117-81-7鄰苯二甲酸二(2-乙基己基)酯Di(2-ethylhexyl)phthalate,DEHP1752650[30]九孔鮑Haliotisdiversicolorsupertexta胚胎發(fā)育EmbryoNOEC21000483.46[79]53-16-7雌酮Estrone,E1321.02[20]青鳉魚(yú)Oryziaslatipes雌性化FemaleNOEC811040.13[77]50-28-2雌二醇17β-estradiol,E2134[21]青鳉魚(yú)Oryziaslatipes卵黃蛋白原VTGLOEC5200～23026.8[78]84-66-2鄰苯二甲酸二乙酯Diethylphthalate,DEP381420[30]九孔鮑Haliotisdiversicolorsupertexta胚胎發(fā)育EmbryoNOEC20000419.07[79]15687-27-1布洛芬Ibuprofen,IBU1417[26]青鳉魚(yú)Oryziaslatipes孵化率HatchabilityNOEC10013214.17[80]58-22-0睪酮Testosterone,TTR3.2[81]靜水椎實(shí)螺Greatpondsnail產(chǎn)卵量EggNOEC0.32110.67[82]131-11-3鄰苯二甲酸二甲酯Dimethylphthalate,DMP173420[32]九孔鮑Haliotisdiversicolorsupertexta胚胎發(fā)育EmbryoNOEC2000048.67[79]117-84-0鄰苯二甲酸二正辛酯Di-n-octylphthalate,DOP114760[34]九孔鮑Haliotisdiversicolorsupertexta胚胎發(fā)育EmbryoNOEC2000045.74[79]70458-96-7諾氟沙星Norfloxacin,NFX6800[15]藍(lán)藻Blue-greenalgae生長(zhǎng)GrowthNOEC160064.25[83]3380-34-5三氯生Triclosan,TCS1023[26]菲律賓蛤仔Ruditapesphilippinarum卵黃蛋白原VTGNOEC30073.41[84]15307-86-5雙氯芬酸Diclofenac,DIC843[28]虹鱒魚(yú)Rainbowtrout組織TissueLOEC460211.83[85]298-46-4卡馬西平Carbamazepine,CMP675[27]大型溞Daphniamagna繁殖ReproductionNOEC50061.35[86]50-27-1雌三醇Estriol,E394[23]青鳉魚(yú)Oryziaslatipes雌性化FemaleNOEC751101.25[77]

3.4篩查結(jié)果及分析

為了不漏掉任何有問(wèn)題的化學(xué)品，篩選水平的評(píng)價(jià)結(jié)果通常比較保守[76]，應(yīng)以文獻(xiàn)報(bào)道中最大檢出濃度作為 EEC 。根據(jù)公式(1)，計(jì)算得到RI，若比值大于1，說(shuō)明風(fēng)險(xiǎn)較高，可能對(duì)水生生物產(chǎn)生潛在的繁殖損傷，比值越大毒性越高；若比值小于1，說(shuō)明風(fēng)險(xiǎn)較小。

RI = EEC / NOEC

(1)

計(jì)算結(jié)果表明，有16種PPCPs的RI>1(見(jiàn)表2)，包括1種抗生素，5種激素類藥物，3種其他藥物和7種PCPs。美國(guó)加州第65號(hào)提案清單將其中的EE2、DBP、DEHP和CMP標(biāo)注為繁殖毒性化學(xué)品，E1、E2和睪酮為致癌化學(xué)品。

由表2可知，盡管抗生素類藥物在我國(guó)地表水檢出率較高，但由于其生物敏感性較低[68]，在我國(guó)目前地表水污染水平下，只有NFX對(duì)藍(lán)藻生長(zhǎng)產(chǎn)生抑制作用，對(duì)地表水生態(tài)環(huán)境影響不大。水生生物對(duì)激素類藥物的敏感性最高，EE2的LOEC值僅為0.03 ng·L-1[77]，而我國(guó)地表水中最大濃度為3 471.9 ng·L-1[19]，RI值為115 730，對(duì)青鳉魚(yú)的繁殖影響極大；睪酮對(duì)凈水椎實(shí)螺的產(chǎn)卵量NOEC值為0.3 ng·L-1[82]，因此盡管地表水檢出濃度僅為3.2 ng·L-1[81]，仍然具有一定的生態(tài)風(fēng)險(xiǎn)。3種其他藥物為IBU、DIC和CMP，其中IBU的RI較高(14.17)，在一定程度上影響珠江中魚(yú)類的種群繁殖。PCPs中NP是典型的內(nèi)分泌干擾物，暴露濃度為100 ng·L-1時(shí)就對(duì)青鳉魚(yú)的VTG產(chǎn)生影響[78]，又由于其較高的檢出濃度，RI高達(dá)1 796，危害程度僅次于EE2；5種PAEs的NOEC值差別不大，對(duì)水生生物的影響程度主要取決于地表水殘留濃度，RI值范圍為5.74～255.31。綜上所述，激素類藥物的NOEC明顯較低，而PCPs的檢出濃度相對(duì)較高。因此，在目前我國(guó)地表水污染水平下，二者對(duì)水生態(tài)環(huán)境的風(fēng)險(xiǎn)最大。

4　展望

(1) 國(guó)外對(duì)污染物篩查體系的研究已經(jīng)相對(duì)成熟，并成功應(yīng)用于實(shí)際工作中，而我國(guó)的污染物篩查方法比較簡(jiǎn)單，對(duì)篩查體系研究較少，尤其缺乏對(duì)繁殖毒性及內(nèi)分泌干擾物類污染物篩查體系的研究。因此，有必要建立完善符合我國(guó)區(qū)域特征的繁殖毒性PPCPs篩查體系，為PPCPs類污染物的生態(tài)風(fēng)險(xiǎn)評(píng)價(jià)提供科學(xué)基礎(chǔ)和技術(shù)支撐。

(2) 目前針對(duì)PPCPs的研究工作主要集中在測(cè)試其環(huán)境濃度水平與研究環(huán)境行為方面，關(guān)于其環(huán)境效應(yīng)及生態(tài)風(fēng)險(xiǎn)的研究仍然處于起步階段，尤其是針對(duì)低劑量長(zhǎng)期暴露下的繁殖毒性效應(yīng)和種群動(dòng)態(tài)變化?，F(xiàn)有的PPCPs毒性數(shù)據(jù)來(lái)自國(guó)外毒性數(shù)據(jù)庫(kù)以及不同文獻(xiàn)，受試物種和實(shí)驗(yàn)終值差別較大，因此，應(yīng)通過(guò)不同營(yíng)養(yǎng)級(jí)區(qū)域特征水生生物(魚(yú)，大型溞，浮游植物)的毒性表征，真實(shí)反映區(qū)域水環(huán)境中PPCPs的環(huán)境效應(yīng)和生態(tài)風(fēng)險(xiǎn)。

(3) 針對(duì)PPCPs特別是具有繁殖毒性及內(nèi)分泌干擾效應(yīng)PPCPs污染物的風(fēng)險(xiǎn)管理，目前還沒(méi)有成熟的理論體系。近年來(lái)一些研究報(bào)道采用環(huán)境歸趨預(yù)測(cè)、PBT分?jǐn)?shù)、Stockholm模型等方法進(jìn)行PPCPs的危害評(píng)估和定性風(fēng)險(xiǎn)評(píng)估?？傮w來(lái)說(shuō)，現(xiàn)有PPCPs的篩選以及評(píng)價(jià)的方法都是基于污染物本身的環(huán)境預(yù)測(cè)濃度或數(shù)據(jù)庫(kù)常規(guī)毒性作為依據(jù)，很少考慮到其對(duì)生物種群動(dòng)態(tài)以及區(qū)域整體環(huán)境產(chǎn)生的危害及生態(tài)風(fēng)險(xiǎn)。如何科學(xué)地使用常規(guī)實(shí)驗(yàn)數(shù)據(jù)以及這些非傳統(tǒng)的測(cè)試終點(diǎn)預(yù)測(cè)生物種群發(fā)生變化的無(wú)效應(yīng)濃度水平，建立生物個(gè)體水平污染物劑量-效應(yīng)關(guān)系和種群水平污染物劑量-效應(yīng)關(guān)系，發(fā)展由個(gè)體水平定量評(píng)估到種群水平效應(yīng)評(píng)價(jià)的生態(tài)風(fēng)險(xiǎn)評(píng)估方法需要我們進(jìn)一步的研究。

通訊作者簡(jiǎn)介：金小偉(1985―)，男，博士，中國(guó)環(huán)境監(jiān)測(cè)總站高級(jí)工程師，主要從事生態(tài)毒理以及生態(tài)風(fēng)險(xiǎn)評(píng)價(jià)的研究，已發(fā)表論文30余篇。

[1]胡洪營(yíng), 王超, 郭美婷. 藥品和個(gè)人護(hù)理用品(PPCPs)對(duì)環(huán)境的污染現(xiàn)狀與研究進(jìn)展[J]. 生態(tài)環(huán)境, 2005, 14(6): 947-952

[2]Daughton C G, Ternes T A. Pharmaceuticals and personal care products in the environment: Agents of subtle change [J]. Environmental Health Perspectives, 1999, 107(6): 907-938

[3]安靖, 周啟星. 藥品及個(gè)人護(hù)理用品(PPCPs)的污染來(lái)源、環(huán)境殘留及生態(tài)毒[J]. 生態(tài)學(xué)雜志, 2009, 28(9): 1878-1890

An J, Zhou Q X. Pollution sources, environmental residues, and ecological toxicity of pharmaceuticals and personal care products (PPCPs): A review [J]. Chinese Journal of Ecology, 2009, 28(9): 1878-1890 (in Chinese)

[4]喻崢嶸. 東江下游某市飲用水中藥品和個(gè)人護(hù)理用品分布及凈化[D]. 北京: 清華大學(xué), 2011: 1-2

Yu Z R. Distribution and purification of pharmaceutical and personal care products (PPCPs) in drinking water [D]. Beijing: Tsinghua University, 2011: 1-2 (in Chinese)

[5]Zhou H, Wu C, Huang X, et al. Occurrence of selected pharmaceuticals and caffeine in sewage treatment plants and receiving rivers in Beijing, China [J]. Water Environment Research, 2010, 82(11): 2239-2248

[6]China Industry Research Net (CIRN). Personal care product market development analysis [R]. China Industry Research Net, 2012

[7]Ternes T A, Meisenheimer M, McDowel D, et al. Removal of pharmaceuticals during drinking water treatment [J]. Environmental Science & Technology, 2002, 36: 3855-3863

[8]Sun J, Luo Q, Wang D H, et al. Occurrences of pharmaceuticals in drinking water sources of major river watersheds, China [J]. Ecotoxicology and Environmental Safety, 2015, 117: 132-140

[9]Santos L H, Araujo A N, Fachini A, et al. Ecotoxicological aspects related to the presence of pharmaceuticals in the aquatic environment [J]. Journal of Hazardous Materials, 2010, 175(1-3): 45-95

[10]Sun L W, Zha J M, Spear P A, et al. Toxicity of the aromatase inhibitor letrozole to Japanese medaka ( Oryzias latipes ) eggs, larvae and breeding adults [J]. Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology, 2007, 145(4): 533-541

[11]Sun L W, Zha J M, Spear P A, et al. Tamoxifen effects on the early life stages and reproduction of Japanese medaka ( Oryzias latipes ) [J]. Environmental Toxicology and Pharmacology, 2007, 24(1): 23-29

[12]王丹, 隋倩, 趙文濤, 等. 中國(guó)地表水環(huán)境中藥物和個(gè)人護(hù)理品的研究進(jìn)展[J]. 科學(xué)通報(bào), 2014, 59(9): 743-751

Wang D, Sui Q, Zhao W T, et al. Pharmaceutical and personal care products in the surface water of China: A review [J]. Chinese Science Bulletin, 2014, 59(9): 743-751 (in Chinese)

[13]Liu H, Zhang G P, Liu C Q, et al. The occurrence of chloramphenicol and tetracyclines in municipal sewage and the Nanming River, Guiyang city, China [J]. Journal of Environmental Monitoring, 2009, 11: 1199-1205

[14]Yang J F, Ying G G, Zhao J L, et al. Spatial and seasonal distribution of selected antibiotics in surface waters of the Pearl Rivers, China [J]. Environmental Science and Health, 2011, 46: 272-280

[15]Zou S, Xu W, Zhang R, et al. Occurrence and distribution of antibiotics in coastal water of the Bohai Bay, China: Impacts of river discharge and aquaculture activities [J]. Environmental Pollution, 2011, 159: 2913-2920

[16]Luo Y, Xu L, Rysz M, et al. Occurrence and transport of tetracycline, sulfonamide, quinolone, and macrolide antibiotics in the Haihe river basin, China [J]. Environmental Science & Technology, 2011, 45: 1827-1833

[17]Minh T B, Leung H W, Loi I H, et al. Richardson, antibiotics in the Hong Kong metropolitan area: Ubiquitous distribution and fate in Victoria Harbour [J]. Marine Pollution Bulletin, 2009, 58: 1052-1062

[18]Yang J F, Ying G G, Zhao J L, et al. Spatial and seasonal distribution of selected antibiotics in surface waters of the Pearl Rivers, China [J]. Journal of Environmental Science and Health, Part B, 2011, 46: 272-280

[19]高會(huì), 那廣水, 方小丹, 等. 大連地區(qū)環(huán)境水體中六種雌激素的殘留特征及隨季節(jié)變化情況[J]. 環(huán)境化學(xué), 2011, 30(12): 2041-2046

Gao H, Na G S, Fang X D, et al. Distribution and seasonal variation of six estrogens in environmental water of Dalian [J]. Environmental Chemistry, 2011, 30(12): 2041-2046 (in Chinese)

[20]Zhang X, Zhang D D, Zhang H, et al. Occurrence, distribution, and seasonal variation of estrogenic compounds and antibiotic residues in Jiulongjiang River, South China [J]. Environmental Science and Pollution Research, 2012, 19: 1392-1404

[21]Zhou X, Lian Z R, Wang J T, et al. Distribution of estrogens along Licun river in Qingdao China [J]. Procedia Environmental Sciences, 2011, 10: 1876-1880

[22]侯麗萍, 劉珊, 方展強(qiáng), 等. 廣東四會(huì)鄧村河水體中雌/雄激素物質(zhì)的含量及分布[J]. 農(nóng)業(yè)環(huán)境科學(xué)學(xué)報(bào), 2013, 32(1): 135-140

Hou L P, Liu S, Fang Z Q, et al. Concentrations and distribution of estrogenic and androgenic chemicals in water collected from Dengcun river, Sihui city, Guangdong province [J]. Journal of Agro-Environment Science, 2013, 32(1): 135-140 (in Chinese)

[23]譚麗超. 水環(huán)境中類固醇激素的污染特征及健康風(fēng)險(xiǎn)評(píng)價(jià)研究[D]. 南京: 南京農(nóng)業(yè)大學(xué), 2011: 49-59

Tan L C. Environmental pollution investigations and environmental risk assessment studies of steroid hormones [D]. Nanjing: Nanjing Agricultural University, 2011: 49-58 (in Chinese)

[24]Zhao J L, Ying G G, Liu Y S, et al. Occurrence and a screening-level risk assessment of human pharmaceuticals in the Pearl River system, South China [J]. Environmental Toxicology and Chemistry, 2010, 29: 1377-1384

[25]Yu Y, Huang Q, Wang Z, et al. Occurrence and behavior of pharmaceuticals, steroid hormones, and endocrine-disrupting personal care products in wastewater and the recipient river water of the Pearl River Delta, South China [J]. Journal of Environmental Monitoring, 2011, 13: 871-878

[26]Peng X, Yu Y, Tang C, et al. Occurrence of steroid estrogens, endocrine-disrupting phenols, and acid pharmaceutical residues in urban river water of the Pearl River Delta, South China [J]. Science of the Total Environment, 2008, 397: 158-166

[27]Zhou X F, Dai C M, Zhang Y L, et al. A preliminary study on the occurrence and behavior of carbamazepine (CBZ) in aquatic environment of Yangtze River Delta, China [J]. Environmental Monitoring and Assessment, 2011, 173: 45-53

[28]Yang Y, Fu J, Peng H, et al. Occurrence and phase distribution of selected pharmaceuticals in the Yangtze Estuary and its coastal zone [J]. Journal of Hazardous Materials, 2011, 190: 588-596

[29]王丹, 隋倩, 呂樹(shù)光, 等. 黃浦江流域典型藥物和個(gè)人護(hù)理品的含量及分布特征[J]. 中國(guó)環(huán)境科學(xué), 2014, 34(7): 1897-1904

Wang D, Sui Q, Lv S G, et al. Concentrations and distribution of selected pharmaceuticals and personal care products in Huangpu River [J]. China Environmental Science, 2014, 34(7): 1897-1904 (in Chinese)

[30]陸繼龍, 郝立波, 王春珍, 等. 第二松花江中下游水體鄰苯二甲酸酯分布特征[J]. 環(huán)境科學(xué)與技術(shù), 2007, 21(30): 35-38

[31]Fang X Y, Ying X, Gerd P, et al. Nonylphenol, bisphenol-A and DDTs in lake Donghu, China [J]. Fresenius Environmental Bulletin, 2005, 14(3): 173-180

[32]Shen Y Y, Xu Q, Yin X Y, et al. Determination and distribution features of phthalate esters in Xuanwu Lake [J]. Journal of Southeast University: Natural Science Edition, 2010, 40(6): 1337-1341

[33]Hu Z, Shi Y, Cai Y, et al. Concentrations, distribution, and bioaccumulation of synthetic musks in the Haihe River of China [J]. Chemosphere, 2011, 84: 1630-1635

[34]王軍良, 徐超, 莊曉偉, 等. 水中鄰苯二甲酸酯污染現(xiàn)狀及高級(jí)氧化降解技術(shù)研究[J]. 工業(yè)水處理, 2011, 31(4): 5-13

[35]王春, 李曉東, 史玉坤, 等. 南通市地表水中鄰苯二甲酸酯類污染狀況研究[J]. 南通大學(xué)學(xué)報(bào)(醫(yī)學(xué)版), 2007, 27(3): 167-170

Wang C, Li X D, Shi Y K, et al. Study on pollution condition of phthalate esters in surface water in Nantong city [J]. Jouna1 of Nantong University (Medical Sciences), 2007, 27(3): 167-170 (in Chinese)

[36]Capleton A C, Courage C, Rumsby P, et al. Prioritising veterinary medicines according to their potential indirect human exposure and toxicity profile [J]. Toxicology Letters, 2006, 163(3): 213- 2231

[37]Bu Q W, Wang D H, Wang Z J. Review of screening systems for prioritizing chemical substances [J]. Critical Reviews in Environmental Science and Technology, 2013, 43(10): 1011-1041

[38]Hansen B G,Haelst A G, Leeuwen K, et al. Priority setting for existing chemicals: European Union risk ranking method [J]. Environmental Toxicology and Chemistry, 1999, 18: 772-779

[39]Kools S A E, Boxall A B A, Moltmann J F, et al. A ranking of European veterinary medicines based on environmental risks [J]. Integrated Environmental Assessment and Management, 2008, 4(4): 399-408

[40]Mitchell R R, Summer C L, Blonde S A, et al. SCRAM: A scoring and ranking system for persistent, bioaccumulative, and toxic substances for the North American Great Lakes: Resulting chemical scores and rankings [J]. Human and Ecological Risk Assessment, 2002, 8: 530-537

[41]Nassef M, Matsumoto S, Seki M, et al. Acute effects of triclosan, diclofenac and carbamazepine on feeding performance of Japanese medaka fish ( Oryzias latipes ) [J]. Chemosphere, 2010, 80(9): 1095-1100

[42]Kim J W, Ishibashi H, Yamauchi R, et al. Acute toxicity of pharmaceutical and personal care products on freshwater crustacean ( Thamnocephalus platyurus ) and fish ( Oryzias latipes ) [J]. Toxicological Sciences, 2009, 34(2): 227-232

[43]Ivanov I, Schaab C, Planitzer S, et al. DNA microarray technology and antimicrobial drug discovery [J]. Pharmacogenomics, 2000, 1(2): 169 -178

[44]Ankley G T, Bennett R S, Erickson R J, et al. Adverse outcome pathways: A conceptual framework to support ecotoxicology research and risk assessment [J]. Environmental Toxicology and Chemistry, 2010, 29: 730-741

[45]Caldwell D J, Mastrocco F. An integrated approach for prioritizing pharmaceuticals found in the environment for risk assessment, monitoring and advanced research [J]. Chemosphere, 2014, 115: 4-12

[46]彭雙清. 危險(xiǎn)度評(píng)定中AOP的概念以及關(guān)于其中文譯名的思考[J]. 中國(guó)藥理學(xué)與毒理學(xué)雜志, 2013, 27(1): 305

[47]Arnot J, Mackay D. Policies for chemical hazard and risk priority setting: Can persistence, bioaccumulation, toxicity, and quantity information be combined [J]. Environment Science and &Technology, 2008, 42(13): 4648-4654

[48]王朋華, 袁濤, 李榮, 等. 水環(huán)境中優(yōu)先控制藥物篩選體系的建立與應(yīng)用[J]. 中國(guó)環(huán)境監(jiān)測(cè), 2008, 24(4): 7-13

Wang P H, Yuan T, Li R, et al. Screening the priority control pharmaceuticals in the aquatic environment [J]. Environment and Monitoring in China, 2008, 24(4): 7-13 (in Chinese)

[49]Bruchet A, Prompsy C, Filippi G, et al. A broad spectrum analytical scheme for the screening of endocrine disruptors (EDs), pharmaceuticals and personal care products in wastewaters and natural waters [J]. Water Science and Technology, 2002, 46: 86-97

[50]Zhong W, Wang D, Xu X, et al. Screening level ecological risk assessment for phenols in surface water of the Taihu lake [J]. Chemosphere, 2010, 80 (9): 998-1005

[51]Baun A, Eriksson E, Ledin A, et al. A methodology for ranking and hazard identification of xenobiotic organic compounds in urban stormwater [J]. Science of the Total Environment, 2006, 370(1): 29-38

[52]Snyder E, Snyder S,Giesy J, et al. SCRAM: A scoring and ranking system for persistent, bioaccumulative, and toxic substances for the North American great lakes. Part I: Structure of the scoring and ranking system [J]. Environmental Science and Pollution Research, 2000, 7(1): 52-61

[53]Snyder E, Snyder S,Giesy J, et al. SCRAM: A scoring and ranking system for persistent, bioaccumulative, and toxic substances for the North American Great Lakes. Part II: Bioaccumulation potential and persistence [J]. Environmental Science and Pollution Research, 2000, 7(2): 116-121

[54]Snyder E, Snyder S,Giesy J, et al. SCRAM: A scoring and ranking system for persistent, bioaccumulative, and toxic substances for the North American Great Lakes. Part III: Acute and subchronic or chronic toxicity [J]. Environmental Science and Pollution Research, 2000, 7(3): 176-184

[55]Snyder E, Snyder S,Giesy J, et al. SCRAM: A scoring and ranking system for persistent, bioaccumulative, and toxic substances for the North American Great Lakes. Part IV: Results from representative chemicals, sensitivity analysis, and discriminatory power [J]. Environmental Science and Pollution Research, 2000, 7(4): 220-224

[56]Victoria B, Crispin H, Neville L, et al. Prioritising anticancer drugs for environmental monitoring and risk assessment purposes [J]. Science of the Total Environment, 2014, 3: 159-170

[57]Ishibashi H, Matsumura N, Hirano M, et al.Effects of triclosan on the early life stages and reproduction of medaka Oryzias latipes and induction of hepatic vitellogenin [J]. Aquatic Toxicology, 2004, 67(2): 167-179

[58]Zha J M, Sun L W, Spear P A, et al. Comparison of ethinylestradiol and nonylphenol effects on reproduction of Chinese rare minnows ( Gobiocypris rarus ) [J]. Ecotoxicology and Environmental Safety, 2008, 71(2) : 390-399

[59]Gooding M P, Newton T J, Bartsch M R, et al. Toxicity of synthetic musks to early life stages of the freshwater mussel Lampsilis cardium [J]. Archives of Environmental Contamination and Toxicology, 2006, 51(4): 549-558

[60]United States Environmental Protection Agency (US EPA). National recommended water quality criteria [S]. Washington DC: US EPA, 2006

[61]Ackermann G E, Schwaiger J, Negele R D, et al. Effects of long-term nonylphenol exposure on gonadal development and biomarkers of estrogenicity in juvenile rainbow trout ( Oncorhynchus mykiss ) [J]. Aquatic Toxicology, 2002, 60(3): 203-221

[62]Jin X W, Wang Y Y, Jin W, et al. Ecological risk of nonylphenol in China surface waters based on reproductive fitness [J]. Environmental Science & Technology, 2014, 48: 1256-1262

[63]Nakma H. Occurrence of synthetic musk fragrances in marine mammals and sharks from Japanese coastal waters [J]. Environmental Science & Technology, 2005, 39(10): 3430-3434

[64]Brozinski J M, Lahti M, Oikari A, et al. Identification and dose dependency of ibuprofen biliary metabolites in rainbow trout [J]. Chemosphere, 2013, 93: 1789-1795

[65]Maruya K A, Vidal D E, Bay S M, et al. Organic contaminants of emerging concern in sediments and flatfish collected near outfalls discharging treated wastewater effluent to the southern California Bight [J]. Environmental Toxicology and Chemistry, 2012, 31: 2683-2688

[66]Brozinski J M, Lahti M, Oikari A, et al. Detection of naproxen and its metabolites in fish bile following intraperitoneal and aqueous exposure [J]. Environmental Science and Pollution Research International, 2011, 18: 811-818

[67]REACH法規(guī)對(duì)CMR/PBT物質(zhì)的控制與企業(yè)應(yīng)對(duì)策略[OL]. http://reach.Chem info.gov. cn/hottopic/show.aspx?xh= 566

[68]Ji K, Kim S, Han S, et al. Risk assessment of chlortetracycline,oxytetracycline, sulfamethazine, sulfathiazole, and erythromycin in aquatic environment: Are the current environmental concentrations safe? [J]. Ecotoxicology, 2012, 21(7): 2031-2050

[69]Segner H, Navas J, Schfers C, et al. Potencies of estrogenic compounds in in vitro screening assays and in life cycle tests with zebrafish in vivo [J]. Ecotoxicology and Environmental Safety, 2003, 54(3): 315-322

[70]金小偉, 王業(yè)耀, 王子健, 等. 淡水水生態(tài)基準(zhǔn)方法學(xué)研究: 繁殖/生殖毒性類化合物水生態(tài)基準(zhǔn)探討[J]. 生態(tài)毒理學(xué)報(bào), 2015, 10(1): 31-39

Jin X W, Wang Y Y, Wang Z J, et al. Methodologies for deriving aquatic life criteria (ACL): Discussion of ACL for chemicals causing reproductive toxicity [J]. Asian Joumal of Ecoloxicology, 2015, 10(1): 31-39 (in Chinese)

[71]Ankley G T, Johnson R D. Small fish models for identifying and assessing the effects of endocrine-disrupting chemicals [J]. Ilar Journal,2004, 45(4): 469-483

[72]Bosker T, Munkiitrick K R, Maclatchy D L. Challenges and opportunities with the use of biomarkers to predict reproductive impairment in fishes exposed to endocrine disrupting substances [J]. Aquatic Toxicology, 2010, 100(1): 9-16

[73]Hutchinson T H, Ankley G T, Segner H, et al. Screening and testing for endocrine disruption in fish-biomarkers as “signposts”, not “traffic lights” in risk assessment [J]. Environmental Health Perspectives, 2006, 114: 106-114

[74]Hartung T. Toxicology for the twenty-first century [J]. Nature, 2009, 460(7252): 208-212

[75]Jin X, Wang Y, Jin W, et al. Ecological risk of nonylphenol in China surface waters based on reproductive fitness [J]. Environmental Science & Technology, 2014, 48(2): 1256-1262

[76]周軍英, 程燕. 農(nóng)藥生態(tài)風(fēng)險(xiǎn)評(píng)價(jià)研究進(jìn)展[J]. 生態(tài)與農(nóng)村環(huán)境學(xué)報(bào), 2009, 25(4): 95-99

Zhou J Y, Cheng Y. Advancement in the study of pesticides ecological risk assessment [J]. Journal of Ecology and Rural Environment, 2009, 25(4): 95-99 (in Chinese)

[77]Metcalfe C D, Metcalfe T L, Kiparissis Y, et al. Estrogenic potency of chemicals detected in sewage treatment plant effluents as determined by in vivo assays with Japanese medaka ( Oryzias latipes ) [J]. Environmental Toxicology and Chemistry, 2001, 20(2): 297-308

[78]Tabata A, Kashiwada S, Ohnishi Y, et al. Estrogenic influences of estradiol-17beta, p-nonylphenol and bis-phenol-A on Japanese medaka ( Oryzias latipes ) at detected environmental concentrations [J]. Water Science and Technology, 2001, 43(2): 109-116

[79]Liu Y, Guan Y, Yang Z, et al.Toxicity of seven phthalate esters to embryonic development of the abalone Haliotis diversicolor supertexta [J]. Ecotoxicology, 2009, 18(3): 293-303

[80]Han S, Choi K, Kim J, et al. Endocrine disruption and consequences of chronic exposure to ibuprofen in Japanese medaka ( Oryzias latipes ) and freshwater cladocerans Daphnia magna and Moina macrocopa [J]. Aquatic Toxicology, 2010, 98(3): 256-264

[81]王玲. 環(huán)境中類固醇類內(nèi)分泌干擾物的檢測(cè)技術(shù)及其降解行為研究[D]. 濟(jì)南: 山東大學(xué), 2007: 68

Wang L. Studies on the new analytical technology for steroids and its degradation behavior in the environment [D]. Jinan: Shandong University, 2007: 68 (in Chinese)

[82]Giusti A, Ducrot V, Joaquim-Justo C. Testosterone levels and fecundity in the hermaphroditic aquatic snail Lymnaea stagnalis exposed to testosterone and endocrine disruptors [J]. Environmental Toxicology and Chemistry, 2013, 32(8): 1740-1745

[83]Ando T, Nagase H, Eguchi K. A novel method using cyanobacteria for ecotoxicity test of veterinary antimicrobial agents [J]. Environmental Toxicology and Chemistry, 2007, 26(4): 601-606

[84]Matozzo V, Formenti A, Donadello G. A multi-biomarker approach to assess effects of triclosan in the clam Ruditapes philippinarum [J]. Marine Environmental Research, 2012, 74: 40-46

[85]Mehinto A C, Hill E M, Tyler C R. Uptake and biological effects of environmentally relevant concentrations of the nonsteroidal anti-inflammatory pharmaceutical diclofenac in rainbow trout ( Oncorhynchus mykiss ) [J]. Environmental Science & Technology, 2010, 44(6): 2176-2182

[86]Dietrich S, Ploessl F, Bracher F. Single and combined toxicity of pharmaceuticals at environmentally relevant concentrations in Daphnia magna - A multigenerational study [J]. Chemosphere, 2010, 79(1): 60-66

◆

Pharmaceuticals and Personal Care Products (PPCPs) Caused Reproductive Toxicity in Surface Water of China: A Review

Liu Na1, Jin Xiaowei2, *, Wang Yeyao1, 2, Lv Yibing2, Yang Qi1

1. School of Water Resources and Environment, China University of Geosciences (Beijing), Beijing 100083, China 2. China National Environmental Monitoring Center, Beijing100012, China

23 March 2015accepted 10 June 2015

It was reported that 144 pharmaceuticals and personal care products (PPCPs) have been detected in Chinese surface waters, including hormones, antibiotics, other pharmaceuticals and personal care products (PCPs).The highest exposure concentration which can be detected even reached at μ g·L-1level, which may lead to endocrine disruption or reproductive toxicity, and then affect the population dynamics of aquatic organisms. In present study, the potential ecological risks of PPCPs were screened and ranked using risk index (RI) methods based on reproductive fitness in Chinese surface water. The result showed that 16 kinds of PPCPs have a high risk which with RI>1 in Chinese surface waters, including 5 hormones, 1 antibiotic, 3 other drugs and 7 PCPs, in which ethinylestradiol (EE2) with the highest RI of 115 730, followed by nonylphenol (NP) with RI of 1 796, and dibutyl phthalate (DBP) with RI of 255.31. High tiered ecological risk assessments are needed to get further evaluation for those PPCPs.

PPCPs; screening system; reproductive toxicity; Chinese surface waters

國(guó)家自然科學(xué)青年基金(21307165)；國(guó)家水體污染控制與治理科技重大專項(xiàng)(2013ZX07502001)；環(huán)境模擬與污染控制國(guó)家重點(diǎn)聯(lián)合實(shí)驗(yàn)室(中國(guó)科學(xué)院生態(tài)環(huán)境研究中心)開(kāi)放基金(14K02ESPCR)

劉娜 (1985-)，女，博士研究生，研究方向?yàn)樯鷳B(tài)毒理及風(fēng)險(xiǎn)評(píng)價(jià)研究，E-mail:liuna_1231@163.com

Corresponding author)， E-mail: jxw85@126.com

10.7524/AJE.1673-5897.20150323014

2015-03-23錄用日期：2015-06-10

1673-5897(2015)6-001-12

X171.5

A

劉娜, 金小偉, 王業(yè)耀, 等. 我國(guó)地表水中藥物與個(gè)人護(hù)理品污染現(xiàn)狀及其繁殖毒性篩查[J]. 生態(tài)毒理學(xué)報(bào)，2015, 10(6): 1-12

Liu N, Jin X W, Wang Y Y, et al. Pharmaceuticals and personal care products (PPCPS) caused reproductive toxicity in surface water of China: A review [J]. Asian Journal of Ecotoxicology, 2015, 10(6): 1-12 (in Chinese)