四氯異苯腈、菲克利與益達胺三種農藥之多重混合毒性評估

Evaluation of Imidacloprid, Hexaconazole and Chlorothalonil Three Pesticides Mixture Toxicity Effects

楊俊宏(Chun-Hung Yang) ； 林天宇(Tian-Yu Lin) ； 蔡韙任(Wei-Ren Tsai)

《臺灣農藥科學》 1期 (2016/12) Pp. 1-23

https://doi.org/10.6671/TPS/2016.001.01

摘要

農藥是保護植物、提高農產品產量與發展農業必需的資材，但也面臨著混合多種農藥施用後超量殘留於蔬果的食入風險。而考量這些具高殘留暴露風險農藥間之不同藥物混合暴露是否可能產生藥物混合交互作用，導致對人類之毒性增加，是評估農藥多重殘留風險最重要的課題。先前研究顯示菲克利、四氯異苯腈與益達胺農藥分別具引起肝、腎與神經毒性之潛在風險。因此，本研究擬驗證探討菲克利、四氯異苯腈與益達胺等3 種不同毒性作用機制農藥混合投予大鼠28 天餵食亞急毒性後，對肝、腎或神經毒性可能產生之多重毒性作用。結果顯示，單一處理菲克利150 mg/kg/day ( 約為ADI 值0.0047 mg/kg/day 之30,000 倍)、四氯異苯腈200 mg/kg/day ( 約為ADI 值0.03 mg/kg/day 之6,700 倍) 或益達胺農藥75 mg/kg/day ( 約為ADI 值0.057 mg/kg/day 之1,250 倍)，分別特異性的產生肝脂肪變性 (fatty change in the liver)、ALT 下降與出現顫抖神經症狀之神經毒性表現，而經分別兩兩混合或混合3 種上述農藥之試驗組對於單一農藥所表現出之特異性毒性表現均不會明顯加重其毒性表現，顯示3 種農藥混合不具劑量相加混合效應，更不具毒性加乘協力作用；而只具同時表現其單一農藥產生之特異性毒性表現。可作為多種農藥殘留之食用風險性安全性參考。

關鍵字

交互作用 ； 協力效應 ； 混合物 ； 劑量相加 ； 累積性風險評估 ； 拮抗作用

並列摘要

Pesticides are indispensable to agriculture as they protect plants from disease and improve agricultural production. However, pesticides are associated with cumulative or mixture risks when excessive amounts of mixed pesticide residues are ingested (typically from consuming fruits and vegetables). Therefore, comprehensive risk assessments of pesticide mixtures are critically important. Previous studies have shown that imidacloprid, hexaconazole, and chlorothalonil pesticides can induce neurotoxic, hepatotoxic, and nephrotoxic reactions, respectively. The present study addresses the mixed neurotoxic, hepatotoxic, and nephrotoxic effects of imidacloprid, hexaconazole, and chlorothalonil by combining these three pesticides (which act independently and have different toxicity modes of action) in a 28-day oral subacute toxicity assay. Treating rats with a combination of 75 mg/kg/day imidacloprid (about 1,250 fold of ADI), 150 mg/kg/day hexaconazole (about 30,000 fold of ADI), and 200 mg/kg/day chlorothalonil (about 6,700 fold of ADI) induced simultaneous clinical sign of convulsions, hepatocyte vacuolations (fatty changes), and reductions in ALT levels. However, there is no evidence that exposure to the combination of these three pesticides can aggravate clinical convulsions, hepatocyte vacuolations, or ALT level hepatotoxicity caused by exposure to a single pesticide or different combinations of two pesticides. Our findings demonstrate that the combination of imidacloprid, hexaconazole, and chlorothalonil pesticides do not have dose additive (cumulative) or synergistic effects in rats.

並列關鍵字

interaction ； synergy ； mixtures ； dose additivity ； accumulation risk assessment ； antagonism