Food Saf (Tokyo). 2016 Mar 30;4(1):30-31. doi: 10.14252/foodsafetyfscj.2016004s. eCollection 2016 Mar.
The Food Safety Commission of Japan (FSCJ) conducted a risk assessment of an insecticide, abamectin (CAS No. 71751-41-2), based on results from various studies. The insecticide is consisted of avermectin Ba (CAS No. 65195-55-3) and avermectin Bb (CAS No. 65195-56-4), both macrolides having a structure of 16-membered ring. Major adverse effects of abamectin observed are neurological symptoms such as tremor/convulsion and mydriasis. FSCJ considered that abamectin causes tremor/convulsion through the GABA-ergic action with hyperpolarization of nerve/muscle cells. Neither carcinogenicity, reproductive toxicity, developmental neurotoxicity nor genotoxicity was observed. Based on the above results, abamectin and its isomeric 8,9-Z avermectin Ba, a photolytic product of avermectin Ba, were identified as chemicals for the residue definition for dietary risk assessment in agricultural products. The lowest value among the no-observed-adverse-effect levels (NOAELs) and the lowest-observed-adverse-effect levels (LOAELs) obtained in all the studies was the LOAEL of 0.12 mg/kg bw/day in a developmental neurotoxicity study in rats. FSCJ specified an acceptable daily intake (ADI) of 0.0006 mg/kg bw/day, applying a safety factor of 200 (10 for species difference, 10 for individual difference, and additional 2 for the use of LOAEL). The lowest NOAEL for adverse effects that would be likely to be elicited by a single oral administration of abamectin was 0.5 mg/kg bw/day consistently obtained in the acute neurotoxicity study in rats, and in the 18-week subacute toxicity study, the 85-day subacute toxicity study and the one-year chronic toxicity study in dogs. FSCJ specified an acute reference dose (ARfD) of 0.005 mg/kg bw, applying a safety factor of 100 to the NOAEL.
日本食品安全委员会（FSCJ）基于各项研究结果，对杀虫剂阿维菌素（化学物质登记号：71751-41-2）进行了风险评估。该杀虫剂由阿维菌素Ba（化学物质登记号：65195-55-3）和阿维菌素Bb（化学物质登记号：65195-56-4）组成，二者均为具有16元环结构的大环内酯类化合物。观察到的阿维菌素的主要不良反应为震颤/惊厥和瞳孔散大等神经症状。FSCJ认为，阿维菌素通过对神经/肌肉细胞进行超极化作用的γ-氨基丁酸（GABA）能作用引发震颤/惊厥。未观察到致癌性、生殖毒性、发育神经毒性和遗传毒性。基于上述结果，阿维菌素及其异构体8,9-Z阿维菌素Ba（阿维菌素Ba的光解产物）被确定为农产品膳食风险评估残留定义的化学物质。在所有研究中获得的未观察到不良反应水平（NOAELs）和观察到不良反应的最低水平（LOAELs）中的最低值，是大鼠发育神经毒性研究中的LOAEL，为0.12 mg/kg体重/天。FSCJ规定的每日允许摄入量（ADI）为0.0006 mg/kg体重/天，采用了200的安全系数（物种差异为10，个体差异为10，使用LOAEL时额外增加2）。在大鼠急性神经毒性研究以及犬的18周亚急性毒性研究、85天亚急性毒性研究和一年慢性毒性研究中，单次口服阿维菌素可能引发的不良反应的最低NOAEL始终为0.5 mg/kg体重/天。FSCJ采用100的安全系数对该NOAEL进行计算，规定急性参考剂量（ARfD）为0.005 mg/kg体重。
