台灣風險分析學會

 

 

 2021年第4期

淺談美國環保署對環境內分泌干擾物和人類健康的觀點(下篇)      

 農業藥物毒物試驗所 呂水淵
   Release: Apr 05, 2021

 

圖2.一種基於“證據權重”的文獻回顧，簡化11種EPA、EDSP 第1階篩選試驗的潛在方法，該文獻涉及測試指南方案中有關化學藥品的影響[4;18]。在這種方法中，最初進行了兩次看門(gatekeeper)分析，即黑頭呆魚短期生殖測試和青春期雄大鼠測試。如果這些均為陰性，則無需其他篩選。這取決於魚的檢測，以檢測雌性素和抑制類固醇生成的化學物質。在青春期雄性檢測中檢測到雄性素和抗雄性素以及會改變甲狀腺功能的化學物質。如果任一看門(gatekeeper)分析均為陽性（在無明顯毒性的情況下），則根據作用方式觸發額外的篩選[4; 16; 18]。（縮寫：T1S-EPA，EDSP一級篩選測定組合; AR-雄性素受體; ARTA(androgen receptor transcriptional antagonist assay)-雄性素受體轉錄拮抗劑測定; T (testosterone)-睾丸激素; PPS(preputial separation)-陰莖包皮分離; LH(luteinizing hormone)-黃體生成激素; T4(thyroxine)-甲狀腺素; T3(triiodothyronine)-三碘甲腺氨酸; TSH (thyroid stimulating hormone)–甲狀腺刺激激素； FH(fathead minnow reproduction test) –黑頭呆魚繁殖試驗； PM(pubertal male assay) –青春期雄性測定； E2 – 17β(estradiol-17β)雌二醇； KT(ketotestosterone) –酮睾酮； H295R(cell line used to assess steroidogenesis in vitro) –用於體外評估類固醇生成的細胞系[48]。

 

圖3.Owens等人(2006) [47]，Robaire等人(1979) [30]，Phelps和Okoko等人(2011) [33]和Wolf等人(2002)的脊椎動物生殖組織中的穩健體內NMDR和明顯的LNT劑量反應[32]。左上圖顯示了用丙酸睾丸酮（皮下注射）處理十天後稱重的五個雄性素依賴性組織的劑量相關反應。這些反應在低劑量範圍內似乎都是線性的。數據來自OECD在15個實驗室進行的實驗室間Hershberger分析驗證研究（n = 90，每個實驗室每劑量6隻大鼠）右上方的面板在長期使用睾丸激素（皮下植入）處理後，顯示出睾丸精子計數的非單調劑量反應（NMDR）。睾丸重量也顯示出相似的NMDR，而血清睾丸激素和LH則沒有。左下圖顯示了餵食中甲基睾丸激素對尼羅羅非魚性別比的影響的NMDR。右下面板。在子宮內施用丙酸睾丸激素（皮下注射）會引起NMDR，從而導致雌性大鼠後代的生殖道畸形和死亡。死亡率僅在雌性後代和青春期後才可見[48]。

 

 

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