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To ensure food safety and facilitate extra-label withdrawal interval (WDI) estimations, a PBPK model for tylosin in broiler chickens and laying hens was developed. The model structure encompassed plasma, crop, gizzard, small intestine, colon, muscle, liver, kidney, fat, rest of body, and an integrated reproductive system consisting of the ovary and oviduct (for hens). This model adequately predicted the pharmacokinetics of tylosin in plasma, tissues, egg yolk, and white under different scenarios in both broilers and layers with determination coefficients of 0.87 and 0.78, respectively. The model was converted to a user-friendly web-based interface. The estimated WDIs were 2.0, 3.0, 4.0, 2.0, and 2.0\u2009d for eggs, kidney, liver, muscle, and fat, respectively, based on FDA tolerance after daily oral administration at 110\u2009mg\/kg tylosin via medicated water for 5 consecutive days in laying hens. This model provides a useful and flexible tool for food safety assessment of tylosin in chickens and lays the groundwork for extrapolating to other drugs in other poultry species.<\/jats:p>","DOI":"10.1093\/toxsci\/kfaf030","type":"journal-article","created":{"date-parts":[[2025,2,27]],"date-time":"2025-02-27T07:57:43Z","timestamp":1740643063000},"page":"279-296","source":"Crossref","is-referenced-by-count":4,"title":["An open-source interactive physiologically based pharmacokinetic model of tylosin in broiler chickens and laying hens"],"prefix":"10.1093","volume":"205","author":[{"given":"Zhicheng","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Environmental and Global Health, College of Public Health and Health Professions, University of Florida , Gainesville, FL 32611,","place":["United States"]},{"name":"Center for Environmental and Human Toxicology, University of Florida , Gainesville, FL 32611,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa A","family":"Mercer","sequence":"additional","affiliation":[{"name":"Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California-Davis , Davis, CA 95616,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa A","family":"Tell","sequence":"additional","affiliation":[{"name":"Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California-Davis , Davis, CA 95616,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8731-8366","authenticated-orcid":false,"given":"Zhoumeng","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Environmental and Global Health, College of Public Health and Health Professions, University of Florida , Gainesville, FL 32611,","place":["United States"]},{"name":"Center for 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