Toxicological Research

Korean Society of Toxicology & Korea Environmental Mutagen Society (한국독성학회)
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Re-evaluation of a microbiological acceptable daily intake for tylosin based on its impact on human intestinal microflora

  • Min Ji Kim (Pesticide and Veterinary Drug Residues Division, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety) ;
  • Ji Young Kim (Pesticide and Veterinary Drug Residues Division, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety) ;
  • Jang Duck Choi (Pesticide and Veterinary Drug Residues Division, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety) ;
  • Guiim Moon (Pesticide and Veterinary Drug Residues Division, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety)
  • Received : 2022.11.27
  • Accepted : 2023.03.29
  • Published : 2024.01.15
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Abstract

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 ㎍/mL, which was mean 50% minimum inhibitory concentration (MIC50), 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 MIC50 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 frst time in Korea based on the revised microbiological risk assessment guidelines and in providing scientifc rationale for the risk management of veterinary drug residues in food.

Keywords

Acknowledgement

This study was supported by a grant from the Ministry of Food and Drug Safety of Korea for 2021 (No. 21161MFDS361). Special thanks are ofered to members of the expert committees for their commitment.

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