人體及生物體內人工合成麝香的全球分布特征

李丹陽,武英欣,汪 濤,鄒紅艷

人體及生物體內人工合成麝香的全球分布特征

李丹陽,武英欣,汪 濤,鄒紅艷*

(天津師范大學,天津市水資源與水環境重點實驗室,天津 300387)

綜述了多種人工合成麝香在全球不同國家和地區人體和生物體內的分布特征,并討論了其生物蓄積性和毒性.結果發現佳樂麝香(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最具代表性的人工合成麝香,這與個人護理產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,人工合成麝香對生物體生長發育有抑制作用,對魚類生命早期產生較高的急性毒性,并且在多種污染存在的情況會導致聯合毒性.在未來的研究中,應該評估低劑量的人工合成麝香長期暴露和復合暴露對生物體的影響,同時還要考慮人工合成麝香代謝產物的毒性,制定環境標準值或生態風險閾值.

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、定香持久已經被廣泛應用于沐浴露、化妝品、洗滌劑、香水等各種個人護理品和日用品中[1].SMs按照化學結構可以分為硝基麝香、多環麝香、大環麝香和脂環麝香四類[2].硝基麝香是開發和應用最早的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),其中應用最多的為二甲苯麝香和酮麝香.20世紀50年代,多環麝香逐漸開始使用,包括佳樂麝香(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,硝基麝香逐漸被多環麝香取代.同時由于對硝基麝香和多環麝香毒性的擔憂,新型SMs即大環麝香和脂環麝香因其與天然麝香結構相似、安全性較高、可降解而逐漸進入市場[4],但由于其成本高、合成難度大、工藝復雜,目前在香料市場中所占份額很少,還沒有被大量的使用.

雖然SMs在產品中所占比例通常低于2%[5],但在全球范圍內使用量較高,且具有難降解性、親脂性、生物積累性,對人體健康和環境造成了潛在的負面影響[6],其中一些SMs已在一些國家被禁止和限制使用.硝基麝香從20世紀90年代開始逐漸減少使用,例如MA由于其神經毒性和對人體潛在的光敏性,在1995年被歐洲委員會禁止使用[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《關于化學品注冊、評估、許可和限制的法規》(即REACH法規)列入限期禁用物質名單[1].我國《中華人民共和國國家標準》(即GB/T 22731-2017)中規定禁止在日用香精中加入萬山麝香(Versalide)、MM、MA、MT、MX[8].在日本,硝基麝香被完全禁止使用,但在美國和加拿大并沒有被完全禁止,例如,它們仍被用于生產美國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和印度用于生產那些價格廉價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屬性,SMs廣泛存在于各種環境介質中.環境中SMs的來源主要包括生活污水的直接排放、以及生活污水與工業廢水的二次排放,從而殘留在廢水中的SMs進入河流、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,會進入污水處理廠的污泥中或沉積到沉積物中[13-15].由于SMs具有較強的親脂性,可富集在脂肪含量高的生物體中,并通過食物鏈進行轉移和積累[16-19].人體中SMs主要通過化妝品和日用品的皮膚接觸和吸收進入體內,另外還會通過呼吸吸入以及攝入污染的食物進入并富集在人體體內[20],長期使用對人體的健康產生影響.自日本學者于1981年首次在日本水域的魚類中檢測出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[34]中頻繁被檢測到.

本文根據已發表文獻,歸納總結并分析了全球范圍內SMs在人體及生物體內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,歸納了其檢測分析方法.針對目前SMs研究中存在的問題,我們進行了分析和討論,并綜合國際法律法規對SMs的管控,對SMs污染研究進行了展望.

1 研究方法

考慮到數據的有效性,本研究收集了關于全球SMs在人體及各生物體內分布的數據,對各種SMs在人體及生物體內的濃度、全球分布特征以及生物蓄積性、毒性和分析方法進行了匯總.文獻主要來源于Web of Science、中國知網、萬方等數據庫,數據發表時間跨度為1981～2021年,數據覆蓋范圍主要包括歐洲、北美洲、亞洲、南極洲.收集的數據按人體、水生生物、哺乳類和植物分類,濃度大部分以ng/g 脂重(lw)計算,血液中的濃度以ng/L計算,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干重數據較多以外,在其他生物體中以脂重為單位的平均濃度數據量占比大.因此,本研究用于繪制全球分布圖和箱線圖時使用統一單位,即平均濃度,ng/g lw.由于大環麝香和脂環麝香的數據非常少,本文主要討論多環麝香和硝基麝香.

2 人體內的人工合成麝香

表1 人體中人工合成麝香的全球分布

續表1

注:a中值濃度;b平均值±標準差;c最大值;dLimit of Detection.n.d.為未檢出.

1993年,Liebl等[35]對德國巴伐利亞州母乳樣品進行了分析,首次在母乳中檢測到SMs.隨著SMs對人體潛在毒性的發現,SMs的人體暴露研究逐漸引起人們的關注,主要集中在母乳、脂肪和血液,其中對母乳中SMs的研究最多,具體見表1.

2.1 母乳

從全球范圍上來看(表1),HHCB的濃度范圍為

具體來說,全球母乳中HHCB濃度最高出現在韓國首爾、平川、安山、濟州地區(<5.00～1346ng/g lw,平均值(299±304) ng/g lw;(見表1),其次為德國慕尼黑(21～1316ng/g lw,平均值115ng/g lw)和美國(<5～917ng/g lw,平均值220ng/g lw).中國的四川和東部長江三角洲與韓國首爾、日本、歐洲國家以及美國母乳中HHCB濃度總體相近[36-41],但中國其他地區母乳中HHCB比韓國、日本、歐洲國家以及美國低大約一個數量級[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,中國四川成都地區母乳中的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、瑞典、丹麥、美國和韓國的母乳中都被檢出,其中德國巴伐利亞州和美國、以及韓國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,一是同一類型的香水產品中SMs的成分和濃度以及使用者使用習慣的地區差異;二是這種濃度的差異可能與不同地區母乳捐贈者存在除皮膚接觸外的其他SMs接觸源,或者與HHCB通過人體皮膚的吸收率可能低于AHTN有關[49].總體上,中國東部地區母乳中麝香化合物濃度高于西南地區,這可能與不同地區的經濟水平和生活方式有關[36,43].

基于全球范圍內對德國的研究最多,在德國母乳中HHCB和AHTN的濃度范圍逐年增加,而MX、MK的中值濃度不斷減少,這與德國較早的對MX和MK實施限制和禁止有關[36,38-39,58].

2.2 脂肪

截止目前對人體脂肪中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最高濃度出現在瑞士(6.7～288ng/g lw),而MK最高濃度出現在德國石勒蘇益格-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到,并且濃度較低.DPMI、AHMI、ATII在人體脂肪中均未被檢測出.對于我國,目前還未有關于脂肪中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、韓國,歐洲的瑞士、德國、奧地利、比利時和美洲的美國、加拿大,樣品采集的時間跨度為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品中使用模式、不同國家的使用習慣和樣品采集時間不同造成的[36,43].研究發現 HHCB和AHTN在個人護理和衛生產品中的含量普遍較高,且HHCB含量高于AHTN[53-55].Lu等人[48]調查了發現在中國82%的個人護理品的分析樣品中發現了SMs,其中HHCB和AHTN分別在73%和65%的樣品中檢測到,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(Kow))比AHTN高,因此人體不同生物基質中SMs的內部暴露差異也與其物理化學性質有關.

此外,有學者還在產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到的HHCB平均濃度比韓國的女性樣本中的濃度低20倍左右[45],同時母體血清濃度也比韓國低得多,中國女性比韓國女性處于更低的SMs暴露率環境中[45,47],這可能與中國女性比韓國女性麝香使用率低有關.另外,在韓國的研究中還發現臍帶血中的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在臍帶血中優先積累,這種積累是在妊娠期間經胎盤轉移到胎兒.因此,產前暴露是新生兒體內麝香的主要來源[45].

3 生物體內的人工合成麝香

由于SMs在日用品中的廣泛和持續使用,使其在水環境中的濃度逐漸升高.由于其親脂性,極易在生物體內累積,并且通過食物鏈傳遞,使其廣泛存在于各生物體中.其中對魚類的檢測最多,其次為雙殼類生物(主要為貽貝、牡蠣、蛤蜊).總體來說,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濃度通常低于檢測限,ADBI、DPMI、AHMI、ATII和OTNE 也較少的在水生生物體內檢測到.

3.1 魚類

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

從全球范圍上來看,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.淡水魚中SMs的濃度高于咸水魚,并且多環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].大部分地區的HHCB和AHTN的濃度比MX和MK高1～2數量級.HHCB和AHTN在較高營養級生物體中被檢出,表明其在環境中比較難降解,并且在哺乳動物等頂級捕食者中富集[74].

具體來說HHCB、AHTN和MX在德國魚類中的平均濃度均高于世界大部分地區.在淡水魚中HHCB濃度最高的是德國石勒蘇益格-荷爾斯泰因鯉魚(高達到160000ng/g lw)[75],其次為德國薩爾河的鯉科魚(18400ng/g lw)[76],這主要是由于薩爾河的集水區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世紀初期SMs產品消耗量的減少.此外,捷克伏爾塔瓦河的鲃魚(2972～10806ng/g lw)[50]和德國薩爾河鯛魚樣本(

在海洋環境中,HHCB和AHTN在海洋魚類中的檢出率高達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自人口稠密的奧斯陸地區,沿海地區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,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最高濃度出現在地中海當地市場的多脂魚類中,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,基于脂質濃度(圖3),HHCB在中國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上海(最高到686ng/g lw)[78].基于濕重濃度時,HHCB和AHTN的最大值分別出現在法國英吉利海峽貽貝[82]和北海貽貝[78]中,濃度分別為14.1和2.5ng/g ww.對于甲殼類生物來說,HHCB的最大脂質濃度在上海基圍蝦中,最高達到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]中也檢測到SMs的存在.

對比不同物種,貽貝中檢測到的SMs濃度要高于魚和蝦.因為貽貝作為底棲生物,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在不同物種體內的濃度差異可能與物種不同的生活習慣和代謝能力相關[83-84].相對于美洲和歐洲國家多基于干重報告SMs的濃度水平,亞洲國家對水生生物的檢測多基于脂重和濕重,由圖3可知,大多數關于亞洲國家的研究中針對HHCB和AHTN濃度的檢測研究較多,而對MX和MK在水生生物體濃度水平分布的關注較少[85].但在中國上海蛤蜊中卻檢測到高濃度的MX和MK,以及在日本貝類中也檢測出低濃度的MX和MK.由此可見,在亞洲地區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硝基麝香在各生物體內的分布特征以及對生物體產生的影響.

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現SMs化合物的殘留.SMs在海洋哺乳動物、陸地哺乳動物、鳥類和卵生動物的殘留普遍較低,這可能是由于SMs在高等營養生物中有更高效的代謝和消除[16-17].HHCB和AHTN是大多數海洋哺乳動物分析樣品中發現的主要化合物(以濕重濃度為主)[17],而MX和MK只在韓國沿海水域中發現[86],其余SMs在生物體中均未檢測到.其中條紋海豚是海洋哺乳動物中HHCB濃度最高的物種,濃度為3.9～ 135ng/g ww,AHTN最高濃度則出現在小須鯨中,為(5.9±3.1) ng/g ww[16].在陸地哺乳動物和鳥類中,只有HHCB和AHTN在生物體內檢測到[17].此外在海龜中也發現了HHCB、AHTN和MK[87].

4 生物蓄積性

根據不同水生生物體和環境介質中SMs的濃度水平可計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物向生物體內的遷移能力[89],進而了解SMs的生物積累性.其中BAFL和BAFw分別指指生物體內以脂質重量和濕重為基礎的濃度與水中自由溶解濃度的比值.BAFL、BAFw數值越大表示SMs更容易在生物體內生物積累.

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,例如在德國北部鯽魚的BAFL為15000～34000[91],中國海河的鯽魚、鯉魚、鰱魚中的BAFL,分別為52370、66030、39400[89],而在美國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HHCB的生物積累性差異性顯著.AHTN的生物積累僅在中國海河中檢測到.而MX、MK分別在德國虹鱒魚[92]和荷蘭的藍鰓太陽魚[93]的BAFL最大,分別是4400、1380.此外,基于濕重來計算.德國石勒蘇益格-荷爾斯泰因聯邦州的一個污水處理廠中MX、MK的BAFw值普遍高于HHCB和AHTN,在鰻魚樣本中MX最大BAFw達到了40000,比該地其他水生生物高1～2數量級[92].在德國赤睛魚中的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在不同物種體內的生物積累程度存在差異.

另外,SMs的代謝產物比其本身更易積累.例如,Biselli等[90]研究了德國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.代謝產物HHCB-lactone的BAFL值(18000～154000)比母體化合物HHCB高一個數量級,這表明HHCB的代謝產物比其母體更容易在生物體內積累.

對于BSAF,相關的研究不多,其中海河鯽魚、鯉魚、鰱魚中HHCB和AHTN的BSAF值略高于太湖、韓國洛東江雙殼類生物和新加坡海峽[32,94-95].根據非離子有機化合物在組織脂質和沉積物有機碳之間的擴散分配,BSAF理論值估計為1.7[96].該值小于1.7表明有機化合物向脂類的分配比預測的少,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解釋,可能是生物富集存在放大效應[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在魚類中的快速轉化和消除有關[76,90].此外,韓國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的SMs主要從沉積物中分離,而不是通過食物鏈進行生物放大[94].而海河地區魚類以及韓國洛東江的部分雙殼類生物的BSAF大于1.7,表明SMs在生物積累的過程中可能存在放大效應.

5 毒性

大量研究表明SMs對生物體有一定的毒性,包括對生物生長發育、內分泌的影響,以及生理毒性(神經毒性)、基因毒性、致癌性、遺傳毒性、光敏性等.在5-d-EC50(半最大效應濃度,EC50)值為0.03～ 0.16mg/L的亞致死濃度下MK、HHCB、AHTN、ADBI對海洋橈足類動物湯氏紡錘水蚤幼蟲發育有強烈的抑制作用,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幼體發育,約比成蟲96-h-LC50(半致死濃度,LC50)值1.9mg/L低100倍,而AHTN對其幼蟲發育沒有影響[100].Qu等[101]研究發現高濃度AHTN(10～400 μg/L)會抑制綠藻生長,從而對海洋生態系統產生潛在威脅.對蚯蚓來說,其死亡率隨HHCB和AHTN暴露濃度和暴露時間的增加而增加,7-d- LC50分別為489.0和573.2μg/g,14-d-LC50分別為392.4和436.3mg/kg.其對蚯蚓的無可見效應濃度(NOEC)分別為105和45μg/g.另外,SMs對蚯蚓繁殖率的抑制作用比生長速率的抑制作用更明顯,對蚯蚓繁殖率NOEC均為30μg/g,最低可見效應濃度(LOEC)均為50μg/g[102].對于魚類,Yamauchi等[103]揭示了幾種SMs對雄性青鳉早期生命階段和肝臟基因表達的影響,表明SMs在其生命早期具有較高的急性毒性.

對于多種污染物存在導致的聯合毒性,目前僅有少數報道.例如,2009年相關研究表明,在無外界因素干擾條件下HHCB和鎘(Cd)對大型水蚤的聯合毒性表現為協同效應[104].此外,Chen等[105]報道了AHTN和Cd對小麥幼苗早期發育的聯合毒性明顯高于單一毒性.

此外,SMs是一種潛在的內分泌干擾物質,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節劑(SERMs),發現一些雌激素受體(ER)具有弱的雌激素活性.之后又發現其在斑馬魚ER的體內和體外有抗雌激素作用[107],在各種細胞系中從0.1μmol/L的濃度開始觀察到抗雌激素作用,但僅在相對較高的濃度(10μmol/L)下才觀察到較弱的雌激素作用.Bitsch等[108]發現,暴露于MX、MK和AHTN可顯著增加人類MCF-7乳腺癌細胞的增殖率,對該乳腺癌細胞的體外試驗顯示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相關,硝基麝香具有弱雌激素作用,并且暴露在硝基麝香中會增加小鼠腫瘤形成的風險.

在動物實驗中發現MX具有致瘤性,這可能是由于基于顯著的肝細胞色素P450酶誘導的非基因毒性機制[110].在麝香酮微核試驗中用人源性肝癌細胞系(Hep G2)研究了MK誘變和共誘變效應,結果表明MK放大了B(a)P在細胞中的遺傳毒性作用,人類接觸MK可能會增加他們對B(a)P和其他多環芳烴的健康危害的易感性[111].

對研究SMs的毒性較為普遍,然而對其副產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測試SMs及其副產品的毒性.Li等[112]首次使用三維定量構效關系的3D-QSAR模型預測SMs轉化副產物的LC50,表明其轉化物比母體更難降解并且具有更高的毒性.因此,日后應重視SMs轉化產物對環境的危害.

6 分析方法

SMs在環境和生物體內廣泛存在,因此其準確定量分析對研究環境、生態、毒性等方面十分重要.生物樣品的組成復雜,且SMs含量水平較低,因此在分析過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個步驟,先從樣品基質中提取分析物,再凈化樣品以去除干擾化合物,最后通過氣相色譜(GC)結合質譜(MS)等儀器進行分離和檢測[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 缺點是消耗溶劑量大[112].SE是一種萃取效率較高的萃取技術.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.但因實驗容器的重復利用,需要大量時間徹底清潔實驗容器,這樣不僅耗時還可能會帶來潛在的污染.因此,SE不適合大量生物樣品的痕量分析[6].PLE是一種先進的溶劑萃取技術.萃取是在高于溶劑沸點的高溫下進行的,從而大大減少了萃取時間和溶劑消耗[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,故需進行凈化處理干擾物.人體樣本通常含有大量蛋白質,所以生物樣品要通過固相萃取(SPE)[52,54,64]、蛋白質沉淀(PPT)[54]或者分散固相萃取(dSPE)[18-19,114]等過程去除樣品中的干擾物.除了SPE和PPT凈化生物樣品之外,也會通過凝膠滲透色譜(GPC),再通過硅膠柱或 SPE小柱進行樣品檢測前的處理[41-42,44,46,51.53,58,61].近幾年有研究者提出用一種結合萃取和凈化的分析方法QuEChERS (快速、簡單、便宜、有效、堅固、安全)技術,該技術可以實現有效萃取,使凈化樣品的時間大大縮短,方法簡便且易于操作,能有效提高樣品處理通量

6.3 檢測方法

由于SMs具有沸點低、半揮發性、熱穩定性的物理性質,因此GC和氣相色譜－質譜聯用(GC－MS)是目前國內外常用的檢測方法[112].

GC常用電子捕獲檢測器(ECD)[57],并且由于硝基麝香含有電負性基團,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,例如僅通過保留時間進行化合物定性,可能造成定性特異性差異.因此,近年來GC在麝香分析中正逐漸被GC－MS所取代[112].

GC－MS是目前SMs分析中應用最廣泛的檢測方法,回收率為60%～ 138%[16-17,41,44,46,51-54,60,61,74,79,90,115].氣相色譜－串聯質譜(GC－MS/MS)在SMs分析中也發揮著重要作用[18,42,64,76,113],串聯質譜的優勢在于:能夠提供足夠的化合物結構信息用于定性分析;特征母離子與子離子一一對應,抗干擾能力強;獨有的多反應監測模式具有選擇性好、信噪比高、檢出限低的特點.因此,串聯質譜在生物樣品復雜基質中痕量SMs分析上的應用日益增加[112].氣相色譜－離子阱串聯質譜(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－高分辨率質譜(GC－HRMS)法測定母乳中3 種麝香化合物(MX, MK, MA),平均回收率為90%～110%,檢測限范圍為2～3ng/glw[116].高分辨率質譜(HRMS)可以提供準確的質量,從而提高選擇性和靈敏度,也已用于合成麝香的分析.

7 結論和展望

7.1 結論

SMs廣泛存在于人體及各種生物體中,其中HHCB、AHTN、MX、MK的檢測率較高.在過去幾十年內,隨著硝基麝香逐漸被HHCB和AHTN等多環麝香取代,濃度(特別是MX和MK)正在下降.在美國和韓國,母乳樣本中合成麝香的水平相對較高,而在中國,血清樣本中合成麝香的水平較高.不同國家人體不同基質以及不同地區生物體中SMs濃度有顯著差異.表明全球不同地區SMs消費模式和習慣不同.在中國人體母乳中硝基麝香MX、MK在整體SMs的檢測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.同樣在雙殼類動物中也得出相似的結論,MX、MK在亞洲分布廣泛度遠遠低于HHCB、AHTN.

7.2 展望

7.2.1 毒性 目前關于SMs毒性研究主要通過相關化合物在動物模型中或實驗室中采用相對較短的暴露時間,很難準確推測SMs對人類及其他生物日常暴露的風險.在未來研究中應評估低劑量SMs長期暴露的影響,評價長期慢性毒性和復合毒性.

此外,大多數的毒理學研究單一SMs對生物的影響,很少考慮污染物之間的相互作用,如協同效應、拮抗效應、濃度依賴效應等.應考慮環境中經常檢測到的污染物與SMs之間的聯合毒性,同時還要考慮SMs代謝產物以及其他新型SMs的毒性,應在與環境相關的暴露水平下對生物體進行更多的研究.

7.2.2 分析檢測方法 當前研究人員所采用的采樣及分析檢測方法存在一定的差異性,報道的生物體內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,不利于進行不同研究之間的橫向對比.因此建立有效的、標準化的取樣、分析檢測方法和數據表征是今后研究中需要解決的問題.并且了解SMs的污染閾值對于促進管理和頒布適當的法律法規非常重要,而大多數研究主要集中在小區域內,很難為國家設定相關的環境標準值或生態風險閾值服務,應深入調查研究SMs的環境影響,采取進一步的環境管理措施.

通過檢測數據表明SMs在生物體內不斷的積累.然而,SMs的生物監測數據仍然匱乏.由于生物樣品的復雜組成、大量大分子化合物如脂肪和蛋白質的存在以及極低水平的SMs對其準確的生物監測提出了巨大的挑戰,這為生物樣品中SMs分析方法的改進提供了更大的空間.為了更好地了解SMs的代謝及其對人類健康的影響,需要在國家甚至全球范圍內對其進行更多的生物監測,生物樣本數量達到數百甚至數千個,這就要求開發更加靈敏、可靠和快速準確處理大量生物樣品的分析方法.

[1] Nakata H, Hinosaka M, Yanagimoto H. Macrocyclic-, polycyclic-, and nitro musks in cosmetics, household commodities and indoor dusts collected from Japan: Implications for their human exposure [J]. Ecotoxicology and Environmental Safety, 2015,111:248-255.

[2] Mónica M, Joaquín B. Determination of synthetic musk fragrances [J]. International journal of environmental analytical chemistry, 2016, 96(11-15):1213-1246.

[3] Posada-Ureta O, Olivares M, Navarro P, et al. Membrane assisted solvent extraction coupled to large volume injection-gas chromatography-mass spectrometry for trace analysis of synthetic musks in environmental water samples [J]. Journal of Chromatography A, 2012,1227(none):38-47.

[4] Hawkins D R, ,Elsom L F, ,Kirkpatrick D, et al. Dermal absorption and disposition of musk ambrette, musk ketone and musk xylene in human subjects [J]. Toxicology Letters, 2002,131:147-151.

[5] 中華人民共和國衛生部.化妝品衛生規范(2007年版) [S]. Ministry of Health of the People's Republic of China. Hygienic code for cosmetics (2007 edition) [S].

[6] Katuri G P, Fan X, Kosarac I, et al. Synthetic Musk Compounds in Human Biological Matrices: Analytical Methods and Occurrence—A Review [J]. Journal of AOAC International, 2020,104:368–383.

[7] European Commission,. Eightieth Commission Directive95/34/EC of 10July 1995adapting to technical progressAnnexes II, III, VI and VII to Council Directive 76/768/ EEC on the approximation of the laws of the Member States relating to cosmetic products. Official Journal of the European Communities L 1995,167:19–21.

[8] 中華人民共和國衛生部.化妝品衛生規范(2017年版) [S]. Ministry of Health of the People's Republic of China. Hygienic code for cosmetics (2017edition) [S].

[9] Taylor K M, Weisskopf M, Shine J. Human exposure to nitro musks and the evaluation of their potential toxicity: an overview [J]. Environmental Health, 2014,13(1):14.

[10] Villa S, Assi L , Ippolito A , et al. First evidences of the occurrence of polycyclic synthetic musk fragrances in surface water systems in Italy: Spatial and temporal trends in the Molgora River (Lombardia Region, Northern Italy) [J]. Science of the Total Environment, 2012,416 (none):137-141.

[11] Sumner N R , Guitart C , Fuentes G , et al. Inputs and distributions of synthetic musk fragrances in an estuarine and coastal environment; a case study [J]. Environmental Pollution, 2010,158(1):215-222.

[12] Hong J H, Lee J Y, Ha H J, et al. Occurrence and Sources of Synthetic Musk Fragrances in the Sewage Treatment Plants and the Han River, Korea [J]. Water, 2021,13(4):392.

[13] Lee I S, Lee S H, Oh J E. Occurrence and fate of synthetic musk compounds in water environment [J]. Water Research, 2010,44(1): 214-222.

[14] Wu S F, Ding W H. Fast determination of synthetic polycyclic musks in sewage sludge and sediments by microwave-assisted headspace solid-phase microextraction and gas chromatography-mass spectrometry [J]. Journal of Chromatography A, 2010,1217(17):2776- 2781.

[15] 王 珺,張曉嵐,郭亞文,等.周.上海城市污水處理廠中合成麝香的分布與來源解析 [J]. 中國環境科學, 2010,30(6):796-801.Wang J, Zhang X L, Guo Y W. Distribbution and source analysis of synthetic musks in Shanghai sewage sludge [J]. China Environmental Science, 2022,42(3):1401-1409.

[16] Nakata H , Sasaki H , Takemura A , et al. Bioaccumulation, temporal trend, and geographical distribution of synthetic musks in the marine environment [J]. Environmental Science & Technology, 2007,41(7): 2216-2222.

[17] Kannan K, Reiner J L, Yun S H, et al. Polycyclic musk compounds in higher trophic level aquatic organisms and humans from the United States [J]. Chemosphere, 2005,61(5):693-700.

[18] Cunha S C, Trabalón L, Jacobs S, et al. UV-filters and musk fragrances in seafood commercialized in Europe Union: Occurrence, risk and exposure assessment [J]. Environmental Research, 2018,161: 399.

[19] Trabalón L, Cano-Sancho G, Pocurull E, et al. Exposure of the population of Catalonia (Spain) to musk fragrances through seafood consumption: Risk assessment [J]. Environmental Research, 2015,143.116-122.

[20] Yan L, Tao Y, Wang W, et al. Concentrations and assessment of exposure to siloxanes and synthetic musks in personal care products from China [J]. Environmental Pollution, 2011,159(12):3522-3528.

[21] Yamagishi T, Miyazaki T, Horii S, et al. Identification of musk xylene and musk ketone in freshwater fish collected from the Tama River, Tokyo [J]. Bulletin of Environmental Contamination & Toxicology, 1981,26(5):656-62.

[22] Lange C, Kuch B, Metzger J W. Occurrence and fate of synthetic musk fragrances in a small German river – ScienceDirect [J]. Journal of Hazardous Materials, 2015,282:34-40.

[23] Zhang H, Bu Q, Wu D, et al. Polycyclic musks in surface water and sediments from an urban catchment in the megacity Beijing, China [J]. Environmental Pollution, 2020,263:114548.

[24] 顧 越,李曉靜,梁高峰,等.淀山湖水、沉積物和魚體中的合成麝香及人體暴露評估 [J]. 環境科學學報, 2017,37(1):388-394. Gu Y, Li X J, Liang G F, et al. Synthetic musk in surface water,sediment,and fish collected from Dianshan Lake and the human exposure assessment [J]. Acta Scientiae Circumstantiae, 2017,37(1): 388-394.

[25] Lyu Y, Ren S, Zhong F, et al. 2021. Synthetic musk fragrances in sediments from a subtropical river-lake system in eastern China: occurrences, profiles, and ecological risks [J]. Environmental Science and Pollution Research, 2020,28(12):14597-14606.

[26] Peck A M, Linebaugh E K, Hornbuckle K C. Synthetic Musk Fragrances in Lake Erie and Lake Ontario Sediment Cores [J]. Environmental Science and Technology, 2006,40(18):5629-5635.

[27] Litz N T, Müller J, B?hmer W. Occurrence of Polycyclic Musks in Sewage Sludge and their Behaviour in Soils and Plants. Part 2: Investigation of Polycyclic Musks in Soils and Plants [J]. Journal of Soils & Sediments, 2007,7(1):36-44.

[28] Ramos S, Homem V, Santos L. Uptake and translocation of UV-filters and synthetic musk compounds into edible parts of tomato grown in amended soils [J]. Science of The Total Environment, 2021,792: 148482.

[29] Balc E, Geniolu M, Sofuoglu S C, et al. Indoor air partitioning of Synthetic Musk Compounds: Gas, particulate matter, house dust, and window film [J]. Science of The Total Environment, 2020,792(10): 138798.

[30] Mcdonough C A, Helm P A, Muir D, et al. Polycyclic Musks in the Air and Water of the Lower Great Lakes: Spatial Distribution and Volatilization from Surface Waters [J]. Environmental Science & Technology, 2016,50(21):11575-11583.

[31] Vallecillos L, Borrull F, Pocurull E. Recent approaches for the determination of synthetic musk fragrances in environmental samples [J]. Trends in Analytical Chemistry, 2015,72:80-92.

[32] Zhang X, Xu Q, Man S, et al. Tissue concentrations, bioaccumulation, and biomagnification of synthetic musks in freshwater fish from Taihu Lake, China [J]. Environmental Science and Pollution Research, 2013,20(1):311-322.

[33] Yao L, Lv Y Z, Zhang L J, et al. Bioaccumulation and risks of 24personal care products in plasma of wild fish from the Yangtze River, China [J]. The Science of the Total Environment, 2019,665 (MAY 15):810-819.

[34] Hu Z, Sm Y, Niu H, et al. Occurrence of synthetic musk fragrances in human blood from 11cities in China [J]. Environmental Toxicology & Chemistry, 2010,29(9):1877-1882.

[35] Liebl B, Ehrenstorfer S. Nitro musks in human milk [J]. Chemosphere, 1993,27(11):2253-2260.

[36] Yin J, Wang H, Zhang J, et al. The occurrence of synthetic musks in human breast milk in Sichuan, China [J]. Chemosphere, 2012,87(9): 1018-1023.

[37] Duedahl-Olesen L, Cederberg T, Pedersen K H, et al. Synthetic musk fragrances in trout from Danish fish farms and human milk [J]. Chemosphere, 2005,61(3):422-431.

[38] Liebl B, Mayer R, Ommer S, et al. Transition of nitro musks and polycyclic musks into human milk [J]. Advances in Experimental Medicine and Biology, 2002,478:289-305.

[39] Rimkus G G, Wolf M. Polycyclic musk fragrances in human adipose tissue and human milk [J]. Chemosphere, 1996,33(10):2033-2043.

[40] Ueno D, Moribe M, Inoue K, et al. Synthetic musk fragrances in human breast milk and adipose tissue from Japan [J]. Interdisciplinary Studies on Environmental Chemistry—Environmental Research in Asia, 2009:247-252.

[41] Lee S, Kim S, Park J, et al. Synthetic musk compounds and benzotriazole ultraviolet stabilizers in breast milk: Occurrence, time– course variation and infant health risk [J]. Environmental research, 2015,140:466-473.

[42] Wang H, Zhang J, Gao F, et al. Simultaneous analysis of synthetic musks and triclosan in human breast milk by gas chromatography tandem mass spectrometry [J]. Journal of Chromatography B, 2011, 879(21):1861-1869.

[43] Yin J, Wang H, Li J, et al. Occurrence of synthetic musks in human breast milk samples from 12provinces in China [J]. Food Additives & Contaminants: Part A, 2016,33(7):1219-1227.

[44] Zhou J, Zeng X, Zheng K, et al. Musks and organochlorine pesticides in breast milk from Shanghai, China: levels, temporal trends and exposure assessment [J]. Ecotoxicology and environmental safety, 2012,84:325-333.

[45] Zhang X, Jing Y, Ma L, et al. Occurrence and transport of synthetic musks in paired maternal blood, umbilical cord blood, and breast milk [J]. International journal of hygiene and environmental health, 2015,218(1):99-106.

[46] Reiner J L, Wong C M, Arcaro K F, et al. Synthetic Musk Fragrances in Human Milk from the United States [J]. Environmental Science & Technology, 2007,41(11):3815-3820.

[47] Kang C S, Lee J H, Kim S K, et al. Polybrominated diphenyl ethers and synthetic musks in umbilical cord serum, maternal serum, and breast milk from Seoul, South Korea [J]. Chemosphere, 2010,80(2): 116-122.

[48] Lu Y, Yuan T, Wang W, et al. Concentrations and assessment of exposure to siloxanes and synthetic musks in personal care products from China [J]. Environmental pollution, 2011,159(12):3522-3528.

[49] Balk F, Ford R A. Environmental risk assessment for the polycyclic musks AHTN and HHCB in the EU: I. Fate and exposure assessment [J]. Toxicology letters, 1999,111(1/2):57-79.

[50] Haj?lová J, ?etková L. Synthetic musks in bioindicators: monitoring data of fish and human milk samples from the Czech Republic [M]//Series Anthropogenic Compounds. Springer, Berlin, Heidelberg, 2004:151-188.

[51] Kuklenyik Z , Bryant X A , Needham L L , et al. SPE/SPME–GC/MS approach for measuring musk compounds in serum and breast milk [J]. Journal of Chromatography B, 2007,858(1/2):177-183.

[52] Helbling K S, Schmid P, Schlatter C. The trace analysis of musk xylene in biological samples: problems associated with its ubiquitous occurrence [J]. Chemosphere, 1994,29(3):477-484.

[53] Schiavone A, Kannan K, Horii Y, et al. Polybrominated diphenyl ethers, polychlorinated naphthalenes and polycyclic musks in human fat from Italy: comparison to polychlorinated biphenyls and organochlorine pesticides [J]. Environmental Pollution, 2010,158(2): 599-606.

[54] Reiner J L, Kannan K. A survey of polycyclic musks in selected household commodities from the United States [J]. Chemosphere, 2006,62(6):867-873.

[55] Roosens L, Covaci A, Neels H. Concentrations of synthetic musk compounds in personal care and sanitation products and human exposure profiles through dermal application [J]. Chemosphere, 2007, 69(10):1540-1547.

[56] Zhang X, Yao Y, Zeng X, et al. Synthetic musks in the aquatic environment and personal care products in Shanghai, China [J]. Chemosphere, 2008,72(10):1553-1558.

[57] Raab U, Preiss U, Albrecht M, et al. Concentrations of polybrominated diphenyl ethers, organochlorine compounds and nitro musks in mother's milk from Germany (Bavaria) [J]. Chemosphere, 2008,72(1): 87-94.

[58] Ott M, Failing K, Lang U, et al. Contamination of Human Milk in Middle Hesse, Germany - A Cross-Sectional Study on the Changing Levels of Chlorinated Pesticides, PCB Congeners and Recent Levels of Nitro Musks [J]. Chemosphere, 1999,38(1):13-32.

[59] Rimkus G, Rimkus B, Wolf M. Nitro musks in human adipose tissue and breast milk [J]. Chemosphere, 1994,28(2):421-432.

[60] Lignell S, Darnerud P O, Aune M, et al. Temporal trends of synthetic musk compounds in mother′ s milk and associations with personal use of perfumed products [J]. Environmental science & technology, 2008, 42(17):6743-6748.

[61] Zhang X, Liang G, Zeng X, et al. Levels of synthetic musk fragrances in human milk from three cities in the Yangtze River Delta in Eastern China [J]. Journal of Environmental Sciences, 2011,23(6):983-990.

[62] Müller S, Schmid P, Schlatter C. Occurrence of nitro and non-nitro benzenoid musk compounds in human adipose tissue [J]. Chemosphere, 1996,33(1):17-28.

[63] Moon H B, Lee D H, Lee Y S, et al. Occurrence and accumulation patterns of polycyclic aromatic hydrocarbons and synthetic musk compounds in adipose tissues of Korean females [J]. Chemosphere, 2012,86(5):485-490.

[64] Katuri G P, Fan X, Siddique S, et al. A selective and sensitive gas chromatography-tandem mass spectrometry method for quantitation of synthetic musks in human serum [J]. Journal of AOAC International, 2020,103(6):1461-1468.

[65] Hutter H P, Wallner P, Moshammer H, et al. Synthetic musks in blood of healthy young adults: relationship to cosmetics use [J]. Science of the total environment, 2009,407(17):4821-4825.

[66] Hutter H P, Wallner P, Hartl W, et al. Higher blood concentrations of synthetic musks in women above fifty years than in younger women [J]. International journal of hygiene and environmental health, 2010,213(2):124-130.

[67] K?fferlein H U, Angerer J. Trends in the musk xylene concentrations in plasma samples from the general population from 1992/1993 to 1998 and the relevance of dermal uptake[J]. International archives of occupational and environmental health, 200177, 74(7): 470-476.

[68] Eisenhardt S, Runnebaum B, Bauer K, et al. Nitromusk compounds in women with gynecological and endocrine dysfunction [J]. Environmental research, 2001,87(3):123-130.

[69] Liu N, Shi Y, Xu L, et al. Occupational exposure to synthetic musks in barbershops, compared with the common exposure in the dormitories and households[J]. Chemosphere, 2013, 93(9): 1804-1810.

[70] Leonards P E G, De Boer J. Synthetic musks in fish and other aquatic organisms [M]//Series Anthropogenic Compounds. Springer, Berlin, Heidelberg, 2004:49-84.

[71] Gatermann R, Hellou J, Hühnerfuss H, et al. Polycyclic and nitro musks in the environment: A comparison between Canadian and European aquatic biota [J]. Chemosphere, 1999,38(14):3431-3441.

[72] Mottaleb M A, Usenko S, O’Donnell J G, et al. Gas chromatography– mass spectrometry screening methods for select UV filters, synthetic musks, alkylphenols, an antimicrobial agent, and an insect repellent in fish [J]. Journal of Chromatography A, 2009,1216(5):815-823.

[73] Klaschka U, Von Der Ohe P C, Bschorer A, et al. Occurrences and potential risks of 16fragrances in five German sewage treatment plants and their receiving waters [J]. Environmental Science and Pollution Research, 2013,20(4):2456-2471.

[74] Nakata H. Occurrence of synthetic musk fragrances in marine mammals and sharks from Japanese coastal waters [J]. Environmental science & technology, 2005,39(10):3430-3434.

[75] Gatermann R, Biselli S, Hühnerfuss H, et al. Synthetic musks in the environment. Part 2: Enantioselective transformation of the polycyclic musk fragrances HHCB, AHTN, AHDI, and ATII in freshwater fish [J]. Archives of environmental contamination and toxicology, 2002,42(4): 447-453.

[76] Rüdel H, B?hmer W, Schr?ter-Kermani C. Retrospective monitoring of synthetic musk compounds in aquatic biota from German rivers and coastal areas [J]. Journal of Environmental Monitoring, 2006,8(8): 812-823.

[77] Subedi B, Du B, Chambliss C K, et al. Occurrence of pharmaceuticals and personal care products in German fish tissue: a national study[J]. Environmental science & technology, 2012, 46(16): 9047-9054.

[78] Zhou J, Wang F, Zeng X, et al. Synthetic Musks in Aquatic Organisms in Shanghai [C]//2011 5th International Conference on Bioinformatics and Biomedical Engineering.

[79] Kallenborn R, Gatermann R, Nygard T, et al. Synthetic musks in Norwegian marine fish samples collected in the vicinity of densely populated area. Fresenius Environmental Bulletin, 2001,10:832-842.

[80] Rimkus G G, Wolf M. Nitro musk fragrances in biota from freshwater and marine environment [J]. Chemosphere, 1995,30(4):641-651.

[81] Shek W M, Murphy M B, Lam J C W, et al. Polycyclic musks in green-lipped mussels (Perna viridis) from Hong Kong [J]. Marine pollution bulletin, 2008,57(6-12):373-380.

[82] Tixier C, Héas-Moisan K, Pollono C, et al. Occurrence of synthetic musks in marine shellfish along French coasts[C]//15th International Conference on Environmental Science and Technology. CEST2017_00909. 2017.

[83] Reiner J L, Kannan K. Polycyclic musks in water, sediment, and fishes from the upper Hudson River, New York, USA[J]. Water, Air,& Soil Pollution, 2011, 214(1): 335-342.

[84] Heberer T. Occurrence, fate, and assessment of polycyclic musk residues in the aquatic environment of urban areas—a review [J]. Acta hydrochimica et hydrobiologica, 2002,30(5/6):227-243.

[85] Yao L, Zhao J L, Liu Y S, et al. Personal care products in wild fish in two main Chinese rivers: bioaccumulation potential and human health risks [J]. Science of the Total Environment, 2018,621:1093-1102.

[86] Moon H B, An Y R, Park K J, et al. Occurrence and accumulation features of polycyclic aromatic hydrocarbons and synthetic musk compounds in finless porpoises (Neophocaena phocaenoides) from Korean coastal waters [J]. Marine pollution bulletin, 2011,62(9):1963- 1968.

[87] Guerranti C, Baini M, Casini S, et al. Pilot study on levels of chemical contaminants and porphyrins in Caretta caretta from the Mediterranean Sea [J]. Marine environmental research, 2014,100:33-37.

[88] Zhang H, Kelly B C. Sorption and bioaccumulation behavior of multi-class hydrophobic organic contaminants in a tropical marine food web [J]. Chemosphere, 2018,199:44-53.

[89] Hu Z, Shi Y, Cai Y. Reprint of: Concentrations, distribution, and bioaccumulation of synthetic musks in the Haihe River of China [J]. Chemosphere, 2011,85(2):262-267.

[90] Biselli S, Gatermann R, Kallenborn R, et al. Biotic and abiotic transformation pathways of synthetic musks in the aquatic environment [M]//Series Anthropogenic Compounds. Springer, Berlin, Heidelberg, 2004:189-211.

[91] Ewald F. Kinetik der Akkumulation und Clearance der polycyclischen Moschus-Duftstoffe Galaxolide und Tonalide in Zebrab?rblingen [D]. Master’s thesis (Diplomarbeit), University of Oldenburg, Germany, 1998.

[92] Rimkus G G, Butte W, Geyer H J. Critical considerations on the analysis and bioaccumulation of musk xylene and other synthetic nitro musks in fish [J]. Chemosphere, 1997,35(7):1497-1507.

[93] Tas J W, Balk F, Ford R A, et al. Environmental risk assessment of musk ketone and musk xylene in the Netherlands in accordance with the EU-TGD [J]. Chemosphere, 1997,35(12):2973-3002.

[94] Lee I S, Kim U J, Oh J E, et al. Comprehensive monitoring of synthetic musk compounds from freshwater to coastal environments in Korea: With consideration of ecological concerns and bioaccumulation [J]. Science of the total environment, 2014,470:1502-1508.

[95] Yamagishi T, Miyazaki T, Horii S, et al. Synthetic musk residues in biota and water from Tama River and Tokyo Bay (Japan)[J]. Archives of environmental contamination and toxicology, 1983, 12(1): 83-89.

[96] ASTM (1997). Standard Test Methods for Measuring the Toxicity of Sediment-associated Contaminants with Freshwater Invertebrates. E1706–95b. In: ASTM Annual Book of Standards (Vol. 11.05, pp. 1138–1220). Philadelphia, PA: American Society for Testing and Materials (ASTM).

[97] Brunson E L, Confield T J, Dwyer E J, et al. Assessing sediments of the upper Mississippi River using field-collected oligochaetes and laboratory-exposed Lumbriculus Variegatus [J]. Archives of Environmental Contamination and Toxicology, 1998,35:191-201.

[98] US EPA. (1998). Methods for Assessing Bioaccumulation of Sediment-associated Contaminants with Freshwa- ter Invertebrates. National Sediment Bioaccumulation Conference Proceedings, United States Environmental Protection Agency (US EPA) 823-R-98–002.

[99] Wollenberger L, Breitholtz M, Kusk K O, et al. Inhibition of larval development of the marine copepod Acartia tonsa by four synthetic musk substances [J]. Science of the Total Environment, 2003,305(1-3): 53-64.

[100]Breitholtz M, Wollenberger L, Dinan L. Effects of four synthetic musks on the life cycle of the harpacticoid copepod Nitocra spinipes [J]. Aquatic Toxicology, 2003,63(2):103-118.

[101]曲玉楹,張彩杰,沈秋岑,等.吐納麝香對東海原甲藻的毒性作用機制 [J]. 中國環境科學, 2022,42(3):1401-1409. Qu Y Y, Zhang C J, Shen Q C, et al. Toxic mechaniam of tonalide on Prorocentrum donghaiense [J]. China Environmental Science, 2022, 42(3):1401-1409.

[102]陳 春,周啟星,劉瀟威,等.多環麝香對蚯蚓的急性和亞急性毒性效應 [J]. 生態毒理學報, 2012,7(4):401-407. Chen C, Zhou Q X, Liu X W, Li S. Acute and Sub-Acute Toxicological Effects of Polycyclic Musks on Earth-worm,Eisenia fetida [J]. Asian Journal of Ecotoxicology, 2012,7(4):401-407.

[103]Yamauchi R, Ishibashi H, Hirano M, et al. Effects of synthetic polycyclic musks on estrogen receptor, vitellogenin, pregnane X receptor, and cytochrome P450 3A gene expression in the livers of male medaka (Oryzias latipes)[J]. Aquatic Toxicology, 2008, 90(4): 261-268.

[104]陳 芳,周啟星.模擬城市徑流中加樂麝香和鎘對大型水蚤的毒性效應 [J]. 中國環境科學, 2009,29(1):58-62.Chen F, Zhou Q X. Toxic effects of galaxolide and cadmium on Daphnia magna under polluting flow conditions containing soil-water interfaces from urban areas [J]. China Environmental Science, 2009, 29(1):58-62.

[105]Chen C, Zhou Q, Cai Z, et al. Effects of soil polycyclic musk and cadmium on pollutant uptake and biochemical responses of wheat (Triticum aestivum) [J]. Archives of environmental contamination and toxicology, 2010,59(4):564-573.

[106]Schreurs R H M M, Quaedackers M E, Seinen W, et al. Transcriptional activation of estrogen receptor ERα and ERβ by polycyclic musks is cell type dependent [J]. Toxicology and Applied Pharmacology, 2002, 183(1):1-9.

[107]Schreurs R H M M, Legler J, Artola-Garicano E, et al. In vitro and in vivo antiestrogenic effects of polycyclic musks in zebrafish [J]. Environmental science & technology, 2004,38(4):997-1002.

[108]Bitsch N, Dudas C, K?rner W, et al. Estrogenic activity of musk fragrances detected by the E-screen assay using human mcf-7cells [J]. Archives of Environmental Contamination and Toxicology, 2002,43 (3):0257-0264.

[109]Taylor K M, Weisskopf M, Shine J. Human exposure to nitro musks and the evaluation of their potential toxicity: an overview [J]. Environmental Health, 2014,13(1):1-7.

[110]Lehman-McKeeman L D, Johnson D R, Caudill D. Induction and inhibition of mouse cytochrome P-450 2B enzymes by musk xylene [J]. Toxicology and applied pharmacology, 1997,142(1):169-177.

[111]Mersch-Sundermann V, Schneider H, Freywald C, et al. Musk ketone enhances benzo (a) pyrene induced mutagenicity in human derived Hep G2cells [J]. Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 2001,495(1/2):89-96.

[112]Li X, Li G, Chen B, et al. 3D-QSAR-aided toxicity assessment of synthetic musks and their transformation by-products [J]. Environmental Science and Pollution Research, 2021,28(41):57530- 57542.

[113]Cunha S C, Fernandes J O, Vallecillos L, et al. Co-occurrence of musk fragrances and UV-filters in seafood and macroalgae collected in European hotspots [J]. Environmental research, 2015,143:65-71.

[114]Angerer J, K?fferlein H U. Gas chromatographic method using electron-capture detection for the determination of musk xylene in human blood samples: Biological monitoring of the general population [J]. Journal of Chromatography B: Biomedical Sciences and Applications, 1997,693(1):71-78.

[115]Saraiva M, Cavalheiro J, Lanceleur L, et al. Synthetic musk in seafood products from south Europe using a quick, easy, cheap, effective, rugged and safe extraction method [J]. Food chemistry, 2016,200:330- 335.

[116]劉洪濤,梁少霞,李夢婷,等.人工合成麝香的分析方法及環境污染現狀 [J]. 分析測試學報, 2017,36(12):1526-1535.

Liu H T, Liang S X, Li M T, Luan T G. Environmental Occurrences of Synthetic Musks and Their Analytical Methods [J]. Journal of Instrumental Analysis, 2017,36(12):1526-1535.

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(1997-),女,河北省邯鄲人,碩士研究生,環境地理學專業.15030065026@163.com.

李丹陽,武英欣,汪 濤,等.人體及生物體內人工合成麝香的全球分布特征 [J]. 中國環境科學, 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

國家自然科學基金資助項目(21906118)

* 責任作者, 副研究員, hongyan.zou@tjnu.edu.cn