雷帕霉素的水解行为及对4种非靶标生物的急性毒性

雷帕霉素为大环内脂类抗生素药剂，对多种人类疾病有效，近年发现其对多种植物病原真菌也有较好的抑制活性，有望开发为微生物源农药用于植物病害的防治，而目前关于雷帕霉素的水解行为及其对非靶标生物的急性毒性还未见报道。为评价雷帕霉素的水解行为及其对非靶标生物的急性毒性，本研究通过室内模拟试验，测定了雷帕霉素在不同pH值、温度、初始浓度及光源中的水解特性，同时测定了其对家蚕、意大利工蜂、斑马鱼及赤子爱胜蚯蚓4种非靶标生物的急性毒性。水解试验结果表明:碱性环境、紫外光照及高温有利于雷帕霉素的水解。当其初始质量浓度为10 mg/L时，半衰期分别为66.63、38.93及77.00 h；初始质量浓度为50 mg/L时，半衰期分别为144.38、105.00及165.00 h。急性毒性试验结果表明:雷帕霉素对家蚕和斑马鱼的96 h-LC₅₀值分别为 386.46和3.50 mg/L (有效成分，下同)；对意大利工蜂的急性经口毒性48 h-LD₅₀值为8.95 μg/bee，急性接触毒性48 h-LD₅₀值为16.79 μg/bee；对赤子爱胜蚯蚓的14 d-LC₅₀值为223. 81 mg/kg。按照 “化学农药环境安全评价准则” (GB/T 31270—2014) 的毒性等级划分标准，雷帕霉素对家蚕、斑马鱼、赤子爱胜蚯蚓的急性毒性分别为 “低毒”、“中毒” 和 “低毒”，对意大利工蜂的急性经口毒性为 “中毒”，急性接触毒性为 “低毒”。研究表明，雷帕霉素属于易降解性药剂，对家蚕、意大利工蜂、斑马鱼及赤子爱胜蚯蚓4种非靶标生物安全。

Hydrolysis behavior of rapamycin and its acute toxicity to four non-target organisms

Rapamycin is a macrolide antibiotic agent, which is effective for many kinds of human diseases. Recently, it has been found that rapamycin has good antibacterial activity against a variety of plant pathogenic fungi. It is expected to become a microbial pesticide for plant diseases. However, there are no reports about the hydrolysis behavior and its acute toxicity to non-target organisms of rapamycin. In order to evaluate the hydrolysis behavior of rapamycin and determine its acute toxicity to non-target organisms, the hydrolysis properties of rapamycin under different pH values, temperatures initial concentrations, and light sources were studied by the indoor simulation test method. Besides, the acute toxicity of rapamycin to four non-target organisms, such as Bombyx mori, Apis melliifera L., Brachydanio rerio and Eisenia foetida were determined. The results showed that alkaline environment,ultraviolet light and high temperature were conducive to the hydrolysis of rapamycin. When the initial mass concentration was 10 mg/L, the hydrolysis half-lives were 66.63, 38.93 and 77.00 h respectively. When the initial mass concentration was 50 mg/L, the hydrolysis half-lives were 144.38, 105.00 and 165.00 h respectively. Acute toxicity test showed that the 96 h-LC₅₀ active ingredients values of rapamycin to B. mori and B. rerio were 386.46 and 3.50 mg a.i./L, respectively. The 14 d-LC₅₀ active ingredients value for E. foetida was 223.81 mg a.i./kg. The acute oral toxicity of 48 h-LD₅₀ active ingredients value to A. melliifera L. was 8.95 μg a.i./bee and acute contact toxicity was 16.79 μg a.i./bee. According to the test guidelines on environmental safety assessment for chemical pesticides (GB/T 31270—2014), The acute toxicity of rapamycin to B. mori, B. rerio, and E. foetida were low toxicity, medium toxicity, and low toxicity respectively. The acute oral toxicity and contact toxicity to A. melliifera L. were medium toxicity and low toxicity respectively. The results showed that rapamycin was a biodegradable agent and was safe to four non-target organisms including: B. mori, A. melliifera L., B. rerio and E. foetida.