淡水青鱂魚暴露於抗流感用藥及其代謝物之繁殖效應評估

Reproductive effect assessment of anti-influenza drug metabolites exposure on freshwater medaka (Oryzias latipes)

吳彥廷(Yen-Ting Wu)

指導教授 ： 陳韋妤

高雄醫學大學/生命科學院/生物醫學暨環境生物學系碩士班/碩士(2016年)

摘要

流行性感冒(Influenza)經傳染後常導致季節性流感及流感大流行之疫情發生，世界各國對流感疫情之預防及治療相當重視，於抗流感藥物中克流感(Tamiflu®)長期受到各國的儲備及使用。當人體服用後將代謝物排出於水域環境中，而其代謝物不易分解。先前多數研究僅對水生生物進行克流感代謝物之急性毒試驗，缺乏流感爆發之環境暴露濃度及暴露情境。本研究目的為評估青鱂魚(Oryzias latipes)長期暴露於克流感代謝物下之生殖影響，本研究設計56天長期暴露毒性試驗將青鱂魚暴露於環境相關之4組克流感代謝物濃度(0.06, 0.3, 90及300 µg/L)並與控制組進行比較，觀測其存活率及成長率，再進行生殖試驗以觀測其產卵量，並以不同暴露情境，將各組魚卵進行21天F1子代孵化試驗，以觀測其孵化狀況並量測初孵化仔魚之體長。本研究結果顯示控制組與暴露組(0.06, 0.3, 90及300 µg/L)之親代存活率及每日體重成長率皆無明顯差異。當暴露濃度高於0.3 µg/L則使每對青鱂魚之總產卵量減少(控制組：110顆；暴露組0.06, 0.3, 90及300 µg/L：95, 75, 89及67顆)，此外F1子代孵化結果顯示，300 µg/L之組別總孵化率有下降趨勢(控制組：86.8%；300 µg/L：40%)，而將魚卵孵化於各自親代所處之水域中顯示，子代初孵化之體長則有顯著降低(控制組：4.4925 mm；暴露組0.06, 0.3, 90及300 µg/L：4.4176, 4.4130, 4.4003及4.3755 mm)，綜合以上結論顯示青鱂魚長期暴露於克流感代謝物並不會影響青鱂魚成魚之存活及成長，但若濃度高於0.3 µg/L將會造成產卵量率降低，且影響下一子代的體長，而暴露濃度若高於300 µg/L則亦使孵化率下降，最終將導致青鱂魚族群數量下降。此外從本研究可推論，最佳觀測點為孵化率，其最高不影響濃度為90 µg/L。建議未來研究可針對青鱂魚之下一世代進行暴露實驗，探討克流感代謝物對青鱂魚世代之影響。此外本研究結果可供季節性流感及流感大爆發情形下之生態風險評估參考。

關鍵字

抗流感藥物 ； 青鱂魚 ； 長期暴露 ； 生殖效應 ； 生態毒理

並列摘要

The seasonal and pandemic influenza conditions usually occurs after influenza was spread. The global country pay a lot of attention on prevention and treatment of influenza. Tamiflu® is one of antivirus drugs, and widely used and stored for flu treatment in many countries. When human intake this medicine, the human could excrete Tamiflu metabolites into the water environment, which is hard to remove in the environment. Most of previous studies investigated how Tamiflu metabolites affect the aquatic organisms in acute toxicity exposure. The experiments lack the environmental relevant exposure situation and scenarios. The purpose of this study was to assess the reproduction effect of medaka (Oryzias latipes) posed by long-term Tamiflu metabolites.
Firstly, this study carried out a 56-day long-term toxicity bioassay to observe the survival and growth rates of the medaka under the environmental relevant Tamiflu metabolite exposure (0.06, 0.3, 90, and 300 µg/L). Secondly, this study carried out reproduction bioassays to observe medaka egg production. Finally, this study carried out the 21-day F1 generation hatchability trial bioassays to observe the hatchability and larvae body length of F1 medaka under different incubation conditions (Tamiflu metabolite concentrations). In the result, there are no difference in the survival and weight growth rates of medaka between the control and all exposure groups. When the exposure concentration was higher than 0.3 µg/L, the total egg production of medaka was significantly decreased (Control：110；exposure groups 0.06, 0.3, 90 and 300 µg/L：95, 75, 89 and 67). In the other hand, the result of F1 generation hatchability trial bioassays showed that the hatching rate had a downward trend in exposure group of 300 µg/L (Control：86.6%；300 µg/L：40%). After the eggs hatching in their own parental water, the larvae body length was significantly shorter than the control group (Control：4.4925 mm；exposure groups 0.06, 0.3, 90 and 300 µg/L：4.4176, 4.4130, 4.4003 and 4.3755 mm). In conclusion, the egg production of medaka was decreased when the exposure concentration was higher than 0.3 µg/L, and the hatching probability was decreased when exposure to 300 µg/L of Tamiflu metabolites. In the other side, the larvae body length of exposure groups were shorter than that of control group. These physiological effects might lead to inhibit the population dynamics of medaka. Otherwise, this study determine that the most suitable endpoint is the hatching rate. With this point of view, this study suggest that the lowest observe effect concentration (LOEC) of Tamiflu metabolites on medaka is 90 µg/L. Furthermore, this study suggest that impact of Tamiflu on F1 generation of medaka should be considered further study. This study provided the insights into the ecological risk assessments under seasonal and pandemic influenza outbreak.

並列關鍵字

Anti-influenza drug ； Medaka (Oryzias latipes) ； Long-term exposure ； Reproductive effect ； Ecotoxicology

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