Kim Min Ji, Kim Ji Young, Choi Jang Duck, Moon Guiim
Pesticide and Veterinary Drug Residues Division, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, 187 Osongsaengmyeong 2-ro, Osong, Cheongju, Chungcheongbuk-do 28159 Republic of Korea.
Toxicol Res. 2023 Aug 2;40(1):23-30. doi: 10.1007/s43188-023-00179-z. eCollection 2024 Jan.
As veterinary drugs available for fish is very restricted, there is growing trials for repurposing livestock drugs as aquatic animal drugs. Tylosin is one of the most effective antibiotics to treat bacterial infections approved for livestock, and would be used in fish. Hence, we investigated the toxicological and microbiological aspects of tylosin to establish health-based guidance value (HBGV) and maximum residue limit (MRL) in fishes, and reevaluated the microbiological acceptable daily intake (mADI) based on updated relevant data and international guildeline. Lastly, exposure assessment was performed to confirm the appropriateness of MRL. By investigating available microbiologcial studies on tylosin, the microbiological point of departure was determined as 0.308 μg/mL, which was mean 50% minimum inhibitory concentration (MIC), obtained from the Food Safety Committee of Japan (FSCJ) evaluation report. Furthermore, as a factor for the derivation of mADI, the volume of colon content was recently changed to 500 mL in compliance with the International Cooperation on Harmonization of Technical Requirements for Registration of Veterinary Medicinal Products (VICH) guidelines. This was previously defined as the mass of colon content (220 g). We applied correction factor 0.224 to the mean MIC for tylosin in the equation of mADI, since the drug is transformed to metabolites with reduced activity prior to entering the colon and bound to fecal materials within the colon of human. The mADI was evaluated as 0.01 mg/kg bw/day. Finally, the hazard index, calculated by dividing the estimated chronic dietary exposure by mADI, did not exceed 100%, suggesting that chronic dietary exposure to tylosin residues from veterinary use was unlikely to be a public health concern. Overall, this study contributes significantly in updating HBGV by application of the concept of mADI for the first time in Korea based on the revised microbiological risk assessment guidelines and in providing scientific rationale for the risk management of veterinary drug residues in food.
The online version contains supplementary material available at 10.1007/s43188-023-00179-z.
由于可用于鱼类的兽药非常有限，将家畜用药重新用作水产动物药物的试验越来越多。泰乐菌素是一种被批准用于家畜治疗细菌感染的最有效的抗生素之一，也将用于鱼类。因此，我们研究了泰乐菌素的毒理学和微生物学方面，以确定鱼类基于健康的指导值（HBGV）和最大残留限量（MRL），并根据最新的相关数据和国际准则重新评估微生物学可接受每日摄入量（mADI）。最后，进行暴露评估以确认MRL的适宜性。通过调查有关泰乐菌素的现有微生物学研究，微生物学出发值被确定为0.308μg/mL，这是从日本食品安全委员会（FSCJ）评估报告中获得的平均50%最小抑菌浓度（MIC）。此外，作为推导mADI的一个因素，根据《兽药注册技术要求国际协调会（VICH）指南》，结肠内容物体积最近改为500 mL。这之前被定义为结肠内容物质量（220 g）。由于该药物在进入结肠之前会转化为活性降低的代谢物并与人类结肠内的粪便物质结合，我们在mADI方程中对泰乐菌素的平均MIC应用了校正因子0.224。mADI评估为0.01 mg/kg体重/天。最后，通过将估计的慢性膳食暴露量除以mADI计算得出的危害指数未超过100%，这表明来自兽医用途的泰乐菌素残留的慢性膳食暴露不太可能成为公共卫生问题。总体而言，本研究通过首次在韩国基于修订后的微生物风险评估指南应用mADI概念显著更新了HBGV，并为食品中兽药残留的风险管理提供了科学依据。
在线版本包含可在10.1007/s43188-023-00179-z获取的补充材料。
