人體及生物體內(nèi)人工合成麝香的全球分布特征

李丹陽(yáng),武英欣,汪 濤,鄒紅艷

人體及生物體內(nèi)人工合成麝香的全球分布特征

李丹陽(yáng),武英欣,汪 濤,鄒紅艷*

(天津師范大學(xué),天津市水資源與水環(huán)境重點(diǎn)實(shí)驗(yàn)室,天津 300387)

綜述了多種人工合成麝香在全球不同國(guó)家和地區(qū)人體和生物體內(nèi)的分布特征,并討論了其生物蓄積性和毒性.結(jié)果發(fā)現(xiàn)佳樂(lè)麝香(HHCB)、吐納麝香(AHTN)、二甲苯麝香(MX)、酮麝香(MK)在各生物體中的檢出率都較高(檢出率范圍為 HHCB:20%～100%、AHTN:7%～100%、MX:6%～95%、MK:3.03%～98%),開許梅龍(DPMI)、薩利麝香(ADBI)、粉檀麝香(AHMI)、特拉斯麝香(ATII)、傘花麝香(MM)、西藏麝香(MT)、葵子麝香(MA)的檢出率低且濃度較低.檢出率較高的4種人工合成麝香在各生物體的濃度水平依次為HHCB>AHTN>MK≈MX,HHCB和AHTN是人體和其他生物體內(nèi)最具代表性的人工合成麝香,這與個(gè)人護(hù)理產(chǎn)品中人工合成麝香的使用模式一致,其次為MX和MK.從生物蓄積性看,人工合成麝香在生物體中的積累和代謝,不同地區(qū)不同物種基于脂重的生物富集因子(BAFL)變化較大.從毒性看,人工合成麝香對(duì)生物體生長(zhǎng)發(fā)育有抑制作用,對(duì)魚類生命早期產(chǎn)生較高的急性毒性,并且在多種污染存在的情況會(huì)導(dǎo)致聯(lián)合毒性.在未來(lái)的研究中,應(yīng)該評(píng)估低劑量的人工合成麝香長(zhǎng)期暴露和復(fù)合暴露對(duì)生物體的影響,同時(shí)還要考慮人工合成麝香代謝產(chǎn)物的毒性,制定環(huán)境標(biāo)準(zhǔn)值或生態(tài)風(fēng)險(xiǎn)閾值.

人體；生物體；人工合成麝香；全球分布

人工合成麝香(SMs)作為天然麝香的替代物,由于其成本低、香味芬芳、定香持久已經(jīng)被廣泛應(yīng)用于沐浴露、化妝品、洗滌劑、香水等各種個(gè)人護(hù)理品和日用品中[1].SMs按照化學(xué)結(jié)構(gòu)可以分為硝基麝香、多環(huán)麝香、大環(huán)麝香和脂環(huán)麝香四類[2].硝基麝香是開發(fā)和應(yīng)用最早的SMs,主要包括二甲苯麝香(MX)、酮麝香(MK)、傘花麝香(MM)、西藏麝香(MT)、葵子麝香(MA),其中應(yīng)用最多的為二甲苯麝香和酮麝香.20世紀(jì)50年代,多環(huán)麝香逐漸開始使用,包括佳樂(lè)麝香(HHCB)、吐納麝香(AHTN)、開許梅龍(DPMI)、薩利麝香(ADBI)、粉檀麝香(AHMI)、特拉斯麝香(ATII),其中HHCB、AHTN使用最多[3].近年來(lái),硝基麝香逐漸被多環(huán)麝香取代.同時(shí)由于對(duì)硝基麝香和多環(huán)麝香毒性的擔(dān)憂,新型SMs即大環(huán)麝香和脂環(huán)麝香因其與天然麝香結(jié)構(gòu)相似、安全性較高、可降解而逐漸進(jìn)入市場(chǎng)[4],但由于其成本高、合成難度大、工藝復(fù)雜,目前在香料市場(chǎng)中所占份額很少,還沒有被大量的使用.

雖然SMs在產(chǎn)品中所占比例通常低于2%[5],但在全球范圍內(nèi)使用量較高,且具有難降解性、親脂性、生物積累性,對(duì)人體健康和環(huán)境造成了潛在的負(fù)面影響[6],其中一些SMs已在一些國(guó)家被禁止和限制使用.硝基麝香從20世紀(jì)90年代開始逐漸減少使用,例如MA由于其神經(jīng)毒性和對(duì)人體潛在的光敏性,在1995年被歐洲委員會(huì)禁止使用[7],MK在2009年也被其添加到化妝品中禁止使用的物質(zhì)清單中,同年IFRA禁止使用持久性和生物累積性化合物MX[6],2011年,MX被歐洲《關(guān)于化學(xué)品注冊(cè)、評(píng)估、許可和限制的法規(guī)》(即REACH法規(guī))列入限期禁用物質(zhì)名單[1].我國(guó)《中華人民共和國(guó)國(guó)家標(biāo)準(zhǔn)》(即GB/T 22731-2017)中規(guī)定禁止在日用香精中加入萬(wàn)山麝香(Versalide)、MM、MA、MT、MX[8].在日本,硝基麝香被完全禁止使用,但在美國(guó)和加拿大并沒有被完全禁止,例如,它們?nèi)员挥糜谏a(chǎn)美國(guó)還未重新配方的非化妝品化合物中,并且某些硝基麝香仍在中國(guó)和印度用于生產(chǎn)那些價(jià)格廉價(jià)的化妝品和日用品中[9].

由于大量使用和其本身的物理化學(xué)屬性,SMs廣泛存在于各種環(huán)境介質(zhì)中.環(huán)境中SMs的來(lái)源主要包括生活污水的直接排放、以及生活污水與工業(yè)廢水的二次排放,從而殘留在廢水中的SMs進(jìn)入河流、湖泊、海洋等地表水體[10-12],還有一部分吸附在顆粒物上的SMs,會(huì)進(jìn)入污水處理廠的污泥中或沉積到沉積物中[13-15].由于SMs具有較強(qiáng)的親脂性,可富集在脂肪含量高的生物體中,并通過(guò)食物鏈進(jìn)行轉(zhuǎn)移和積累[16-19].人體中SMs主要通過(guò)化妝品和日用品的皮膚接觸和吸收進(jìn)入體內(nèi),另外還會(huì)通過(guò)呼吸吸入以及攝入污染的食物進(jìn)入并富集在人體體內(nèi)[20],長(zhǎng)期使用對(duì)人體的健康產(chǎn)生影響.自日本學(xué)者于1981年首次在日本水域的魚類中檢測(cè)出MX和MK之后[21],SMs開始在全球的水體[10,22-23]、沉積物[24-26]、土壤[27-28]、空氣[29-30]、水生生物[31-33]和人體內(nèi)[34]中頻繁被檢測(cè)到.

本文根據(jù)已發(fā)表文獻(xiàn),歸納總結(jié)并分析了全球范圍內(nèi)SMs在人體及生物體內(nèi)的污染水平和分布特征,并且討論了其生物蓄積性及其毒性,歸納了其檢測(cè)分析方法.針對(duì)目前SMs研究中存在的問(wèn)題,我們進(jìn)行了分析和討論,并綜合國(guó)際法律法規(guī)對(duì)SMs的管控,對(duì)SMs污染研究進(jìn)行了展望.

1 研究方法

考慮到數(shù)據(jù)的有效性,本研究收集了關(guān)于全球SMs在人體及各生物體內(nèi)分布的數(shù)據(jù),對(duì)各種SMs在人體及生物體內(nèi)的濃度、全球分布特征以及生物蓄積性、毒性和分析方法進(jìn)行了匯總.文獻(xiàn)主要來(lái)源于Web of Science、中國(guó)知網(wǎng)、萬(wàn)方等數(shù)據(jù)庫(kù),數(shù)據(jù)發(fā)表時(shí)間跨度為1981～2021年,數(shù)據(jù)覆蓋范圍主要包括歐洲、北美洲、亞洲、南極洲.收集的數(shù)據(jù)按人體、水生生物、哺乳類和植物分類,濃度大部分以ng/g 脂重(lw)計(jì)算,血液中的濃度以ng/L計(jì)算,還有一部分研究以濕重(ww)、干重(dw)為單位.由于各研究中使用的濃度單位不同,且除魚類中HHCB和AHTN干重?cái)?shù)據(jù)較多以外,在其他生物體中以脂重為單位的平均濃度數(shù)據(jù)量占比大.因此,本研究用于繪制全球分布圖和箱線圖時(shí)使用統(tǒng)一單位,即平均濃度,ng/g lw.由于大環(huán)麝香和脂環(huán)麝香的數(shù)據(jù)非常少,本文主要討論多環(huán)麝香和硝基麝香.

2 人體內(nèi)的人工合成麝香

表1 人體中人工合成麝香的全球分布

續(xù)表1

注:a中值濃度;b平均值±標(biāo)準(zhǔn)差;c最大值;dLimit of Detection.n.d.為未檢出.

1993年,Liebl等[35]對(duì)德國(guó)巴伐利亞州母乳樣品進(jìn)行了分析,首次在母乳中檢測(cè)到SMs.隨著SMs對(duì)人體潛在毒性的發(fā)現(xiàn),SMs的人體暴露研究逐漸引起人們的關(guān)注,主要集中在母乳、脂肪和血液,其中對(duì)母乳中SMs的研究最多,具體見表1.

2.1 母乳

從全球范圍上來(lái)看(表1),HHCB的濃度范圍為

具體來(lái)說(shuō),全球母乳中HHCB濃度最高出現(xiàn)在韓國(guó)首爾、平川、安山、濟(jì)州地區(qū)(<5.00～1346ng/g lw,平均值(299±304) ng/g lw;(見表1),其次為德國(guó)慕尼黑(21～1316ng/g lw,平均值115ng/g lw)和美國(guó)(<5～917ng/g lw,平均值220ng/g lw).中國(guó)的四川和東部長(zhǎng)江三角洲與韓國(guó)首爾、日本、歐洲國(guó)家以及美國(guó)母乳中HHCB濃度總體相近[36-41],但中國(guó)其他地區(qū)母乳中HHCB比韓國(guó)、日本、歐洲國(guó)家以及美國(guó)低大約一個(gè)數(shù)量級(jí)[42-45].歐洲、美洲母乳中HHCB的濃度普遍高于AHTN[48].但在Yin等[36]和Wang等[42]研究中,中國(guó)四川成都地區(qū)母乳中的AHTN濃度高于HHCB,但其中值濃度偏低,在捷克AHTN的濃度范圍為<10～565ng/g lw,中值濃度(67ng/g lw)大于四川(11.5ng/g lw).MX和MK在德國(guó)、瑞典、丹麥、美國(guó)和韓國(guó)的母乳中都被檢出,其中德國(guó)巴伐利亞州和美國(guó)、以及韓國(guó)首爾母乳樣品中濃度較高[35,46-47].造成全球麝香分布情況有差異的原因有兩點(diǎn),一是同一類型的香水產(chǎn)品中SMs的成分和濃度以及使用者使用習(xí)慣的地區(qū)差異;二是這種濃度的差異可能與不同地區(qū)母乳捐贈(zèng)者存在除皮膚接觸外的其他SMs接觸源,或者與HHCB通過(guò)人體皮膚的吸收率可能低于AHTN有關(guān)[49].總體上,中國(guó)東部地區(qū)母乳中麝香化合物濃度高于西南地區(qū),這可能與不同地區(qū)的經(jīng)濟(jì)水平和生活方式有關(guān)[36,43].

基于全球范圍內(nèi)對(duì)德國(guó)的研究最多,在德國(guó)母乳中HHCB和AHTN的濃度范圍逐年增加,而MX、MK的中值濃度不斷減少,這與德國(guó)較早的對(duì)MX和MK實(shí)施限制和禁止有關(guān)[36,38-39,58].

2.2 脂肪

截止目前對(duì)人體脂肪中SMs的研究較少(表1),人體脂肪中HHCB的濃度均比AHTN的濃度高,其中美國(guó)紐約和錫耶納HHCB的平均濃度是AHTN的3倍左右.歐洲人體脂肪中HHCB和AHTN濃度較高,意大利錫耶納分別達(dá)到了5～ 1435ng/g lw(平均(361±467) ng/g lw)和5～931ng/g lw (平均(132±264) ng/g lw).MX最高濃度出現(xiàn)在瑞士(6.7～288ng/g lw),而MK最高濃度出現(xiàn)在德國(guó)石勒蘇益格-荷爾斯泰因(10～220ng/g lw).MA、MM、MT、ADBI只在瑞士人體的脂肪樣品中檢測(cè)到,并且濃度較低.DPMI、AHMI、ATII在人體脂肪中均未被檢測(cè)出.對(duì)于我國(guó),目前還未有關(guān)于脂肪中SMs的研究.

2.3 血液

Helbling等[52]1994年首次在人體血液中檢測(cè)到SMs,MX在血漿和血脂中的濃度范圍分別為66～270pg/g和12～49ng/g.由表1可知,人體血液中SMs的研究主要集中在亞洲的中國(guó)、韓國(guó),歐洲的瑞士、德國(guó)、奧地利、比利時(shí)和美洲的美國(guó)、加拿大,樣品采集的時(shí)間跨度為1992～2014年.

同上述母乳和脂肪一樣,HHCB和AHTN在人體血液中的濃度和檢出率較高,濃度范圍分別為

人體中這些SMs濃度的差異可能是由這些麝香化合物在各產(chǎn)品中使用模式、不同國(guó)家的使用習(xí)慣和樣品采集時(shí)間不同造成的[36,43].研究發(fā)現(xiàn) HHCB和AHTN在個(gè)人護(hù)理和衛(wèi)生產(chǎn)品中的含量普遍較高,且HHCB含量高于AHTN[53-55].Lu等人[48]調(diào)查了發(fā)現(xiàn)在中國(guó)82%的個(gè)人護(hù)理品的分析樣品中發(fā)現(xiàn)了SMs,其中HHCB和AHTN分別在73%和65%的樣品中檢測(cè)到,其次為HHCB-lactone和MK,且HHCB是最主要的化合物,其濃度占總麝香濃度的52%,AHTN是第二豐富的化合物(占比24%)[48,56].除此之外,HHCB的親脂性(即辛醇-水分配系數(shù)(Kow))比AHTN高,因此人體不同生物基質(zhì)中SMs的內(nèi)部暴露差異也與其物理化學(xué)性質(zhì)有關(guān).

此外,有學(xué)者還在產(chǎn)婦血和臍帶血中檢出了SMs的存在.例如,Zhang等[45]和Kang等[47]分別研究了上海和韓國(guó)女性母體和臍帶血清中的SMs,上海女性臍帶血清樣本中檢測(cè)到的HHCB平均濃度比韓國(guó)的女性樣本中的濃度低20倍左右[45],同時(shí)母體血清濃度也比韓國(guó)低得多,中國(guó)女性比韓國(guó)女性處于更低的SMs暴露率環(huán)境中[45,47],這可能與中國(guó)女性比韓國(guó)女性麝香使用率低有關(guān).另外,在韓國(guó)的研究中還發(fā)現(xiàn)臍帶血中的SMs濃度明顯高于母體血液,在上海臍帶血清中HHCB的平均濃度大約是母體血清中濃度的2倍,表明HHCB在臍帶血中優(yōu)先積累,這種積累是在妊娠期間經(jīng)胎盤轉(zhuǎn)移到胎兒.因此,產(chǎn)前暴露是新生兒體內(nèi)麝香的主要來(lái)源[45].

3 生物體內(nèi)的人工合成麝香

由于SMs在日用品中的廣泛和持續(xù)使用,使其在水環(huán)境中的濃度逐漸升高.由于其親脂性,極易在生物體內(nèi)累積,并且通過(guò)食物鏈傳遞,使其廣泛存在于各生物體中.其中對(duì)魚類的檢測(cè)最多,其次為雙殼類生物(主要為貽貝、牡蠣、蛤蜊).總體來(lái)說(shuō),HHCB和AHTN在魚類中濃度最高、變化范圍大,雙殼類生物中的貽貝次之,在鳥類中濃度最低.MA、MM、MT濃度通常低于檢測(cè)限,ADBI、DPMI、AHMI、ATII和OTNE 也較少的在水生生物體內(nèi)檢測(cè)到.

3.1 魚類

1981年Yamagishi等[21]首次在日本東京的淡水魚中發(fā)現(xiàn)MX和MK.迄今為止,SMs已經(jīng)在世界上大多數(shù)地方的水生生物體內(nèi)被廣泛檢出,包括亞洲、歐洲、美洲以及南極洲,其中歐洲關(guān)于SMs的研究最多(圖1).水生生物體內(nèi)最具代表性的SMs為HHCB和AHTN,其次為MX和MK,其他SMs只在少數(shù)樣品中檢測(cè)到,而且濃度較低.

從全球范圍上來(lái)看,基于脂重單位(圖2),歐洲魚類樣本中SMs的濃度普遍高于其他地區(qū).淡水魚中SMs的濃度高于咸水魚,并且多環(huán)麝香的濃度普遍高于硝基麝香.SMs之間的濃度差異在淡水物種中通常更大,主要是由于淡水環(huán)境受污水處理廠出水影響較大,靠近污水處理廠的生物中可檢測(cè)到高濃度的SMs[70],因此,污水處理廠廢水中的水生生物含有的麝香含量明顯更高[22,50,71-73].大部分地區(qū)的HHCB和AHTN的濃度比MX和MK高1～2數(shù)量級(jí).HHCB和AHTN在較高營(yíng)養(yǎng)級(jí)生物體中被檢出,表明其在環(huán)境中比較難降解,并且在哺乳動(dòng)物等頂級(jí)捕食者中富集[74].

具體來(lái)說(shuō)HHCB、AHTN和MX在德國(guó)魚類中的平均濃度均高于世界大部分地區(qū).在淡水魚中HHCB濃度最高的是德國(guó)石勒蘇益格-荷爾斯泰因鯉魚(高達(dá)到160000ng/g lw)[75],其次為德國(guó)薩爾河的鯉科魚(18400ng/g lw)[76],這主要是由于薩爾河的集水區(qū)有大量的污水處理廠,但在之后幾年中,薩爾河的麝香殘留量明顯下降,在2003年下降到6680ng/g lw[76],下降的主要原因是21世紀(jì)初期SMs產(chǎn)品消耗量的減少.此外,捷克伏爾塔瓦河的鲃魚(2972～10806ng/g lw)[50]和德國(guó)薩爾河鯛魚樣本(

在海洋環(huán)境中,HHCB和AHTN在海洋魚類中的檢出率高達(dá)100%.此外,奧斯陸峽灣的大西洋鱈魚中HHCB和AHTN濃度最高分別為132～1510和81～380ng/g lw,這主要由于大西洋鱈魚樣本來(lái)自人口稠密的奧斯陸地區(qū),沿海地區(qū)受到挪威家庭和城市污水排放的影響較大[79].基于干重濃度時(shí),歐洲意大利北海海域比目魚的HHCB干重濃度最大,為12.3～414.4ng/g dw (平均濃度58.8ng/g dw)[18],而AHTN最高濃度出現(xiàn)在地中海當(dāng)?shù)厥袌?chǎng)的多脂魚類中,為

圖1 魚類中人工合成麝香的全球分布(ng/g lw)

圖2 魚類中人工合成麝香的全球分布箱線圖

3.2 雙殼類生物

在雙殼類生物中,基于脂質(zhì)濃度(圖3),HHCB在中國(guó)香港的貽貝樣本中濃度最高(247～6080ng/g lw)[81],AHTN和MK在加拿大蛤蜊樣本中測(cè)得的濃度最高,分別為1100和17700ng/g lw[71],而MX的最高濃度分布在中國(guó)上海(最高到686ng/g lw)[78].基于濕重濃度時(shí),HHCB和AHTN的最大值分別出現(xiàn)在法國(guó)英吉利海峽貽貝[82]和北海貽貝[78]中,濃度分別為14.1和2.5ng/g ww.對(duì)于甲殼類生物來(lái)說(shuō),HHCB的最大脂質(zhì)濃度在上?；鶉r中,最高達(dá)到798ng/g lw,AHTN在龍蝦中的濃度最大為419ng/g lw[78].另外,在淡水螺[78]和章魚[18]中也檢測(cè)到SMs的存在.

對(duì)比不同物種,貽貝中檢測(cè)到的SMs濃度要高于魚和蝦.因?yàn)橘O貝作為底棲生物,受沉積物污染程度影響較大,沉積物中麝香濃度普遍高于地表水[78].此外,SMs在不同物種體內(nèi)的濃度差異可能與物種不同的生活習(xí)慣和代謝能力相關(guān)[83-84].相對(duì)于美洲和歐洲國(guó)家多基于干重報(bào)告SMs的濃度水平,亞洲國(guó)家對(duì)水生生物的檢測(cè)多基于脂重和濕重,由圖3可知,大多數(shù)關(guān)于亞洲國(guó)家的研究中針對(duì)HHCB和AHTN濃度的檢測(cè)研究較多,而對(duì)MX和MK在水生生物體濃度水平分布的關(guān)注較少[85].但在中國(guó)上海蛤蜊中卻檢測(cè)到高濃度的MX和MK,以及在日本貝類中也檢測(cè)出低濃度的MX和MK.由此可見,在亞洲地區(qū)硝基麝香在水生生物中仍然存在.因此,在今后的研究中仍不能忽視亞洲地區(qū)硝基麝香在各生物體內(nèi)的分布特征以及對(duì)生物體產(chǎn)生的影響.

圖3 雙殼類生物中人工合成麝香的全球分布圖(ng/g lw))

3.3 其他生物

在處于食物鏈頂端的生物體中也可以發(fā)現(xiàn)SMs化合物的殘留.SMs在海洋哺乳動(dòng)物、陸地哺乳動(dòng)物、鳥類和卵生動(dòng)物的殘留普遍較低,這可能是由于SMs在高等營(yíng)養(yǎng)生物中有更高效的代謝和消除[16-17].HHCB和AHTN是大多數(shù)海洋哺乳動(dòng)物分析樣品中發(fā)現(xiàn)的主要化合物(以濕重濃度為主)[17],而MX和MK只在韓國(guó)沿海水域中發(fā)現(xiàn)[86],其余SMs在生物體中均未檢測(cè)到.其中條紋海豚是海洋哺乳動(dòng)物中HHCB濃度最高的物種,濃度為3.9～ 135ng/g ww,AHTN最高濃度則出現(xiàn)在小須鯨中,為(5.9±3.1) ng/g ww[16].在陸地哺乳動(dòng)物和鳥類中,只有HHCB和AHTN在生物體內(nèi)檢測(cè)到[17].此外在海龜中也發(fā)現(xiàn)了HHCB、AHTN和MK[87].

4 生物蓄積性

根據(jù)不同水生生物體和環(huán)境介質(zhì)中SMs的濃度水平可計(jì)算出水生生物生物富集因子(BAFs)以及生物-沉積物富集因子(BSAFs)[88],其反映了沉積物中有機(jī)物向生物體內(nèi)的遷移能力[89],進(jìn)而了解SMs的生物積累性.其中BAFL和BAFw分別指指生物體內(nèi)以脂質(zhì)重量和濕重為基礎(chǔ)的濃度與水中自由溶解濃度的比值.BAFL、BAFw數(shù)值越大表示SMs更容易在生物體內(nèi)生物積累.

不同物種基于脂重的BAFL變化較大,這可能是由于不同生物之間積累模式不同和組織類型的影響[83,88-90].HHCB在鯽魚、鯉魚和鰱魚這些魚類中有較高的BAFL,例如在德國(guó)北部鯽魚的BAFL為15000～34000[91],中國(guó)海河的鯽魚、鯉魚、鰱魚中的BAFL,分別為52370、66030、39400[89],而在美國(guó)紐約州的哈德遜河上游的貽貝、淡水石首魚、鯰魚中有較低的BAFL(即261～7060)[83],表明不同物種對(duì)HHCB的生物積累性差異性顯著.AHTN的生物積累僅在中國(guó)海河中檢測(cè)到.而MX、MK分別在德國(guó)虹鱒魚[92]和荷蘭的藍(lán)鰓太陽(yáng)魚[93]的BAFL最大,分別是4400、1380.此外,基于濕重來(lái)計(jì)算.德國(guó)石勒蘇益格-荷爾斯泰因聯(lián)邦州的一個(gè)污水處理廠中MX、MK的BAFw值普遍高于HHCB和AHTN,在鰻魚樣本中MX最大BAFw達(dá)到了40000,比該地其他水生生物高1～2數(shù)量級(jí)[92].在德國(guó)赤睛魚中的HHCB、AHTN、MX、MK的生物積累因子都最低,分別是20、40、290、60[92].由此可見,SMs在不同物種體內(nèi)的生物積累程度存在差異.

另外,SMs的代謝產(chǎn)物比其本身更易積累.例如,Biselli等[90]研究了德國(guó)北部某污水池中生物群的BAFL,其中生物體中HHCB的BAFL范圍為1700～59000.代謝產(chǎn)物HHCB-lactone的BAFL值(18000～154000)比母體化合物HHCB高一個(gè)數(shù)量級(jí),這表明HHCB的代謝產(chǎn)物比其母體更容易在生物體內(nèi)積累.

對(duì)于BSAF,相關(guān)的研究不多,其中海河鯽魚、鯉魚、鰱魚中HHCB和AHTN的BSAF值略高于太湖、韓國(guó)洛東江雙殼類生物和新加坡海峽[32,94-95].根據(jù)非離子有機(jī)化合物在組織脂質(zhì)和沉積物有機(jī)碳之間的擴(kuò)散分配,BSAF理論值估計(jì)為1.7[96].該值小于1.7表明有機(jī)化合物向脂類的分配比預(yù)測(cè)的少,代表可能存在生物稀釋作用,而大于1.7則表明該化合物的吸收不能僅用分配理論來(lái)解釋,可能是生物富集存在放大效應(yīng)[97-98].在太湖、新加坡海峽的魚類中BSAF值均低于1.7,這可能與HHCB和AHTN在魚類中的快速轉(zhuǎn)化和消除有關(guān)[76,90].此外,韓國(guó)洛東江的雙殼類生物中BSAF值也低于1.7,表明雙殼類生物體內(nèi)的SMs主要從沉積物中分離,而不是通過(guò)食物鏈進(jìn)行生物放大[94].而海河地區(qū)魚類以及韓國(guó)洛東江的部分雙殼類生物的BSAF大于1.7,表明SMs在生物積累的過(guò)程中可能存在放大效應(yīng).

5 毒性

大量研究表明SMs對(duì)生物體有一定的毒性,包括對(duì)生物生長(zhǎng)發(fā)育、內(nèi)分泌的影響,以及生理毒性(神經(jīng)毒性)、基因毒性、致癌性、遺傳毒性、光敏性等.在5-d-EC50(半最大效應(yīng)濃度,EC50)值為0.03～ 0.16mg/L的亞致死濃度下MK、HHCB、AHTN、ADBI對(duì)海洋橈足類動(dòng)物湯氏紡錘水蚤幼蟲發(fā)育有強(qiáng)烈的抑制作用,具有極高的毒性[99].此外,HHCB在0.02mg/L濃度下影響哈氏橈足類Nitocra spinipes幼體發(fā)育,約比成蟲96-h-LC50(半致死濃度,LC50)值1.9mg/L低100倍,而AHTN對(duì)其幼蟲發(fā)育沒有影響[100].Qu等[101]研究發(fā)現(xiàn)高濃度AHTN(10～400 μg/L)會(huì)抑制綠藻生長(zhǎng),從而對(duì)海洋生態(tài)系統(tǒng)產(chǎn)生潛在威脅.對(duì)蚯蚓來(lái)說(shuō),其死亡率隨HHCB和AHTN暴露濃度和暴露時(shí)間的增加而增加,7-d- LC50分別為489.0和573.2μg/g,14-d-LC50分別為392.4和436.3mg/kg.其對(duì)蚯蚓的無(wú)可見效應(yīng)濃度(NOEC)分別為105和45μg/g.另外,SMs對(duì)蚯蚓繁殖率的抑制作用比生長(zhǎng)速率的抑制作用更明顯,對(duì)蚯蚓繁殖率NOEC均為30μg/g,最低可見效應(yīng)濃度(LOEC)均為50μg/g[102].對(duì)于魚類,Yamauchi等[103]揭示了幾種SMs對(duì)雄性青鳉早期生命階段和肝臟基因表達(dá)的影響,表明SMs在其生命早期具有較高的急性毒性.

對(duì)于多種污染物存在導(dǎo)致的聯(lián)合毒性,目前僅有少數(shù)報(bào)道.例如,2009年相關(guān)研究表明,在無(wú)外界因素干擾條件下HHCB和鎘(Cd)對(duì)大型水蚤的聯(lián)合毒性表現(xiàn)為協(xié)同效應(yīng)[104].此外,Chen等[105]報(bào)道了AHTN和Cd對(duì)小麥幼苗早期發(fā)育的聯(lián)合毒性明顯高于單一毒性.

此外,SMs是一種潛在的內(nèi)分泌干擾物質(zhì),有一定的雌激素和抗雌激素作用.Schreurs等[106]將 AHTN和 HHCB作為選擇性雌激素受體調(diào)節(jié)劑(SERMs),發(fā)現(xiàn)一些雌激素受體(ER)具有弱的雌激素活性.之后又發(fā)現(xiàn)其在斑馬魚ER的體內(nèi)和體外有抗雌激素作用[107],在各種細(xì)胞系中從0.1μmol/L的濃度開始觀察到抗雌激素作用,但僅在相對(duì)較高的濃度(10μmol/L)下才觀察到較弱的雌激素作用.Bitsch等[108]發(fā)現(xiàn),暴露于MX、MK和AHTN可顯著增加人類MCF-7乳腺癌細(xì)胞的增殖率,對(duì)該乳腺癌細(xì)胞的體外試驗(yàn)顯示MK、MX和MX的主要代謝物(pamino-MX)具有雌激素活性.Taylor等[109]研究表明血液中硝基麝香的水平與黃體激素水平呈負(fù)相關(guān),硝基麝香具有弱雌激素作用,并且暴露在硝基麝香中會(huì)增加小鼠腫瘤形成的風(fēng)險(xiǎn).

在動(dòng)物實(shí)驗(yàn)中發(fā)現(xiàn)MX具有致瘤性,這可能是由于基于顯著的肝細(xì)胞色素P450酶誘導(dǎo)的非基因毒性機(jī)制[110].在麝香酮微核試驗(yàn)中用人源性肝癌細(xì)胞系(Hep G2)研究了MK誘變和共誘變效應(yīng),結(jié)果表明MK放大了B(a)P在細(xì)胞中的遺傳毒性作用,人類接觸MK可能會(huì)增加他們對(duì)B(a)P和其他多環(huán)芳烴的健康危害的易感性[111].

對(duì)研究SMs的毒性較為普遍,然而對(duì)其副產(chǎn)物的毒性研究極為有限.因此需要一種可靠且具有成本效益的方法來(lái)測(cè)試SMs及其副產(chǎn)品的毒性.Li等[112]首次使用三維定量構(gòu)效關(guān)系的3D-QSAR模型預(yù)測(cè)SMs轉(zhuǎn)化副產(chǎn)物的LC50,表明其轉(zhuǎn)化物比母體更難降解并且具有更高的毒性.因此,日后應(yīng)重視SMs轉(zhuǎn)化產(chǎn)物對(duì)環(huán)境的危害.

6 分析方法

SMs在環(huán)境和生物體內(nèi)廣泛存在,因此其準(zhǔn)確定量分析對(duì)研究環(huán)境、生態(tài)、毒性等方面十分重要.生物樣品的組成復(fù)雜,且SMs含量水平較低,因此在分析過(guò)程中需要清除生物樣品中的干擾物.SMs分析一般程序包括3個(gè)步驟,先從樣品基質(zhì)中提取分析物,再凈化樣品以去除干擾化合物,最后通過(guò)氣相色譜(GC)結(jié)合質(zhì)譜(MS)等儀器進(jìn)行分離和檢測(cè)[6].

6.1 樣品提取

生物樣品的處理方法采用不同的萃取方法,如液液萃取(LLE)、索氏萃取(SE)、加壓液體萃取(PLE)又稱加速溶劑萃取(ASE)等方法.

LLE因其簡(jiǎn)單、多用途而成為生物樣品中SMs提取最常用的方法之一,SMs化合物的極性較小,故需使用的極性較弱的萃取溶劑,LLE 缺點(diǎn)是消耗溶劑量大[112].SE是一種萃取效率較高的萃取技術(shù).例如,采用SE從脂肪、魚類、雙殼類生物樣本中提取SMs[16-17,51,53,74,78,81].回收率為60%～138%,脂肪、魚類和雙殼檢出限分別為1.0～5.0ng/g ww、0.1～ 0.8ng/g ww、0.1～ 19.0ng/g lw.但因?qū)嶒?yàn)容器的重復(fù)利用,需要大量時(shí)間徹底清潔實(shí)驗(yàn)容器,這樣不僅耗時(shí)還可能會(huì)帶來(lái)潛在的污染.因此,SE不適合大量生物樣品的痕量分析[6].PLE是一種先進(jìn)的溶劑萃取技術(shù).萃取是在高于溶劑沸點(diǎn)的高溫下進(jìn)行的,從而大大減少了萃取時(shí)間和溶劑消耗[42,75,113].

6.2 樣品凈化

由于生物樣品含有較多的脂肪和大分子化合物,故需進(jìn)行凈化處理干擾物.人體樣本通常含有大量蛋白質(zhì),所以生物樣品要通過(guò)固相萃取(SPE)[52,54,64]、蛋白質(zhì)沉淀(PPT)[54]或者分散固相萃取(dSPE)[18-19,114]等過(guò)程去除樣品中的干擾物.除了SPE和PPT凈化生物樣品之外,也會(huì)通過(guò)凝膠滲透色譜(GPC),再通過(guò)硅膠柱或 SPE小柱進(jìn)行樣品檢測(cè)前的處理[41-42,44,46,51.53,58,61].近幾年有研究者提出用一種結(jié)合萃取和凈化的分析方法QuEChERS (快速、簡(jiǎn)單、便宜、有效、堅(jiān)固、安全)技術(shù),該技術(shù)可以實(shí)現(xiàn)有效萃取,使凈化樣品的時(shí)間大大縮短,方法簡(jiǎn)便且易于操作,能有效提高樣品處理通量

6.3 檢測(cè)方法

由于SMs具有沸點(diǎn)低、半揮發(fā)性、熱穩(wěn)定性的物理性質(zhì),因此GC和氣相色譜－質(zhì)譜聯(lián)用(GC－MS)是目前國(guó)內(nèi)外常用的檢測(cè)方法[112].

GC常用電子捕獲檢測(cè)器(ECD)[57],并且由于硝基麝香含有電負(fù)性基團(tuán),采用ECD能靈敏地檢出,大大降低了分析方法的檢出限.Angerer等[114]選用ECD分析了血液中MX,結(jié)果顯示,該方法檢出限為0.1ng/L.但GC也存在局限,例如僅通過(guò)保留時(shí)間進(jìn)行化合物定性,可能造成定性特異性差異.因此,近年來(lái)GC在麝香分析中正逐漸被GC－MS所取代[112].

GC－MS是目前SMs分析中應(yīng)用最廣泛的檢測(cè)方法,回收率為60%～ 138%[16-17,41,44,46,51-54,60,61,74,79,90,115].氣相色譜－串聯(lián)質(zhì)譜(GC－MS/MS)在SMs分析中也發(fā)揮著重要作用[18,42,64,76,113],串聯(lián)質(zhì)譜的優(yōu)勢(shì)在于:能夠提供足夠的化合物結(jié)構(gòu)信息用于定性分析;特征母離子與子離子一一對(duì)應(yīng),抗干擾能力強(qiáng);獨(dú)有的多反應(yīng)監(jiān)測(cè)模式具有選擇性好、信噪比高、檢出限低的特點(diǎn).因此,串聯(lián)質(zhì)譜在生物樣品復(fù)雜基質(zhì)中痕量SMs分析上的應(yīng)用日益增加[112].氣相色譜－離子阱串聯(lián)質(zhì)譜(GC-IT-MS/MS)也在雙殼類樣品中定量分析SMs中使用,回收率范圍為 47%～ 117%[19].

采用氣相色譜－高分辨率質(zhì)譜(GC－HRMS)法測(cè)定母乳中3 種麝香化合物(MX, MK, MA),平均回收率為90%～110%,檢測(cè)限范圍為2～3ng/glw[116].高分辨率質(zhì)譜(HRMS)可以提供準(zhǔn)確的質(zhì)量,從而提高選擇性和靈敏度,也已用于合成麝香的分析.

7 結(jié)論和展望

7.1 結(jié)論

SMs廣泛存在于人體及各種生物體中,其中HHCB、AHTN、MX、MK的檢測(cè)率較高.在過(guò)去幾十年內(nèi),隨著硝基麝香逐漸被HHCB和AHTN等多環(huán)麝香取代,濃度(特別是MX和MK)正在下降.在美國(guó)和韓國(guó),母乳樣本中合成麝香的水平相對(duì)較高,而在中國(guó),血清樣本中合成麝香的水平較高.不同國(guó)家人體不同基質(zhì)以及不同地區(qū)生物體中SMs濃度有顯著差異.表明全球不同地區(qū)SMs消費(fèi)模式和習(xí)慣不同.在中國(guó)人體母乳中硝基麝香MX、MK在整體SMs的檢測(cè)濃度中占比小于歐洲和美洲.魚類中硝基麝香MK主要分布在歐洲和北美洲,而其在亞洲分布較少,HHCB、AHTN在全球的分布都很廣泛.同樣在雙殼類動(dòng)物中也得出相似的結(jié)論,MX、MK在亞洲分布廣泛度遠(yuǎn)遠(yuǎn)低于HHCB、AHTN.

7.2 展望

7.2.1 毒性 目前關(guān)于SMs毒性研究主要通過(guò)相關(guān)化合物在動(dòng)物模型中或?qū)嶒?yàn)室中采用相對(duì)較短的暴露時(shí)間,很難準(zhǔn)確推測(cè)SMs對(duì)人類及其他生物日常暴露的風(fēng)險(xiǎn).在未來(lái)研究中應(yīng)評(píng)估低劑量SMs長(zhǎng)期暴露的影響,評(píng)價(jià)長(zhǎng)期慢性毒性和復(fù)合毒性.

此外,大多數(shù)的毒理學(xué)研究單一SMs對(duì)生物的影響,很少考慮污染物之間的相互作用,如協(xié)同效應(yīng)、拮抗效應(yīng)、濃度依賴效應(yīng)等.應(yīng)考慮環(huán)境中經(jīng)常檢測(cè)到的污染物與SMs之間的聯(lián)合毒性,同時(shí)還要考慮SMs代謝產(chǎn)物以及其他新型SMs的毒性,應(yīng)在與環(huán)境相關(guān)的暴露水平下對(duì)生物體進(jìn)行更多的研究.

7.2.2 分析檢測(cè)方法 當(dāng)前研究人員所采用的采樣及分析檢測(cè)方法存在一定的差異性,報(bào)道的生物體內(nèi)SMs的濃度水平基于不同的單位(干重、濕重、脂重),所采取的生物體組織樣品也有所不同,不利于進(jìn)行不同研究之間的橫向?qū)Ρ?因此建立有效的、標(biāo)準(zhǔn)化的取樣、分析檢測(cè)方法和數(shù)據(jù)表征是今后研究中需要解決的問(wèn)題.并且了解SMs的污染閾值對(duì)于促進(jìn)管理和頒布適當(dāng)?shù)姆煞ㄒ?guī)非常重要,而大多數(shù)研究主要集中在小區(qū)域內(nèi),很難為國(guó)家設(shè)定相關(guān)的環(huán)境標(biāo)準(zhǔn)值或生態(tài)風(fēng)險(xiǎn)閾值服務(wù),應(yīng)深入調(diào)查研究SMs的環(huán)境影響,采取進(jìn)一步的環(huán)境管理措施.

通過(guò)檢測(cè)數(shù)據(jù)表明SMs在生物體內(nèi)不斷的積累.然而,SMs的生物監(jiān)測(cè)數(shù)據(jù)仍然匱乏.由于生物樣品的復(fù)雜組成、大量大分子化合物如脂肪和蛋白質(zhì)的存在以及極低水平的SMs對(duì)其準(zhǔn)確的生物監(jiān)測(cè)提出了巨大的挑戰(zhàn),這為生物樣品中SMs分析方法的改進(jìn)提供了更大的空間.為了更好地了解SMs的代謝及其對(duì)人類健康的影響,需要在國(guó)家甚至全球范圍內(nèi)對(duì)其進(jìn)行更多的生物監(jiān)測(cè),生物樣本數(shù)量達(dá)到數(shù)百甚至數(shù)千個(gè),這就要求開發(fā)更加靈敏、可靠和快速準(zhǔn)確處理大量生物樣品的分析方法.

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Global distribution of synthetic musks in organisms and human bodies.

LI Dan-yang, WU Ying-xin, WANG Tao, ZOU Hong-yan*

(Tianjin Key Laboratory of Water Resources and Environment, Tianjin Normal University, Tianjin 300387, China)., 2023,43(8)：4267～4279

The distribution patterns of various synthetic musks in humans and organisms around the world are summarized and the associated bioaccumulation and toxicity are discussed. Galaxolide (HHCB), tonalide (AHTN), musk xylene (MX) and musk ketone (MK) often have the highest detection frequencies in all organisms (HHCB: 20～100%; AHTN: 7～100%; MX: 6～95%; MK: 3～98%) while other synthetic musks such as cashmeran (DPMI), celestolide (ADBI), phantolide (AHMI), traseolide (ATII), musk moskene (MM), musk tibetene (MT) and musk ambrette (MA) have lower detection frequencies and concentrations. Being the most representative synthetic musks in humans and other organisms, the levels of HHCB and AHTN were consistent with their use patterns. The lipid-weight based bioaccumulation factor (BAFL) varied greatly among different species in different regions, caused by different metabolisms and tissue sampled. Meanwhile, synthetic musks could impose inhibitory effects on the growth and development of organisms, have acute toxicity in the early life of fish and produce synergic toxicity in the presence of multiple contaminants. Future studies might focus on the evaluation of long-term toxicity and combined exposures to these low-concentration synthetic musks on organisms. More attention should be also taken on the toxicity of metabolites. Furthermore, it is necessary to develop the relevant environmental criteria or ecological risk thresholds.

human body；living organisms；synthetic musks；global distribution

X503

A

1000-6923(2023)08-4267-13

李丹陽(yáng)(1997-),女,河北省邯鄲人,碩士研究生,環(huán)境地理學(xué)專業(yè).15030065026@163.com.

李丹陽(yáng),武英欣,汪 濤,等.人體及生物體內(nèi)人工合成麝香的全球分布特征 [J]. 中國(guó)環(huán)境科學(xué), 2023,43(7):4267-4279.

Li D Y, Wu Y X, Wang T, et al. Global distribution of synthetic musks in organisms and human bodies [J]. China Environmental Science, 2023,43(7):4267-4279.

2023-01-16

國(guó)家自然科學(xué)基金資助項(xiàng)目(21906118)

* 責(zé)任作者, 副研究員, hongyan.zou@tjnu.edu.cn