Progress 09/01/23 to 08/31/24
Outputs
Target Audience:The target audience for FARAD includes veterinarians, extension specialists, government and industry regulators as well as producers throughout all parts of the food animal industries. Veterinarians may submit questions for expert mediated consultations by FARAD via a nationwide toll-free hotline (1.888.873.2723) or through an internet based online submission portal. The data bank, which is updated and maintained regularly, is readily searchable and allows for curated information to be accessed and considered by trained FARAD experts who provide guidance in response to inquiries from veterinarians about potential residue problems associated with situations involving contaminant exposure or legal extralabel drug therapy in food producing animal species. In addition, online and mobile-friendly apps (VetGRAM) provide access to a database of FDA-approved drug uses in animals. Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided?
Nothing Reported
How have the results been disseminated to communities of interest?The web-based resources developed and maintained by UF FARAD are readily available to the public through our websites. We also work on a daily basis with collaborating institutions to compile and update the data bank that is utilized by trained FARAD experts to provide guidance in response to inquiries from veterinarians regarding potential residue issues associated with contaminants or legal extralabel drug use in food producing species. Papers were published in peer reviewed journals to disseminate FARAD-generated data to target audiences in the veterinary and scientific communities, and interactive web-based PBPK models were published online and are freely available for other researchers or industry personnel to utilize. What do you plan to do during the next reporting period to accomplish the goals?The project continues in a no-cost extension phase and during this we will complete the remaining project goals. We will continue to maintain and upgrade FARAD web-based services, maintain the central database of FDA-approved drugs, and contribute to the national FARAD objectives in collaboration with the other FARAD centers. There were some delays to complete the ongoingwork, primarily due to delays in Visa processing and recruitment for incoming Postdoctoral fellows, as well as both a Postdoctoral fellowand a research scientist who had been scheduled to work on this project leaving UF fornew positions. Work will continue on the conversion of developed pharmacologic models into user-friendly web-based interfaces so that the FARAD responders can use these interfaces to predict withdrawal intervals. We will also continue our work on a generic interactive physiologically-based pharmakinetic platform that allows FARAD responders to run simulations and predict withdrawal intervals for different drugs efficiently and rapidly. These projects are important, as FARAD receives thousands of calls a year, and it is imperative to provide timely and quality responses based on user-friendly scientific tools.
Impacts
What was accomplished under these goals?
Impact: The Food Animal Residue Avoidance Databank (FARAD) is a collaborative university-based food safety program that is coordinated and delivered by faculty and staff at five US Universities. Throughout its 42-year existence, FARAD has continued to evolve to meet the changing demands of providing accurate, timely and reliable service to both the veterinary profession and food animal industry stakeholders. At present, the program is managed through a very close collaboration of personnel at Colleges of Veterinary Medicine at the University of California-Davis (UCD), University of Florida (UF), North Carolina State University (NCSU), and Virginia-Maryland (VM), as well as Kansas State University-Olathe (KSUO). The core mission of FARAD is to protect the American public by promoting the production of safe, animal-derived human food products (milk, eggs, meat, honey, etc.) that are devoid of violative or potentially unsafe chemical residues, including drugs, pesticides, environmental contaminants, natural toxins and other harmful substances. In order to carry out this mission, the FARAD team collates, analyzes and interprets the most up-to-date information and uses that unique data repository to provide accurate and timely expert advice to assist veterinarians who are faced with situations that could cause unsafe chemical residues in human food products. In addition, FARAD maintains and provides an array of complete information resources for veterinarians, extension specialists, farmers, regulatory personnel and others who are the stewards of our nation's expansive commercial food animal industries and the growing number of small backyard livestock operations. Throughout over four decades of delivering this program, FARAD has continued to develop increased sophistication with respect to (1) acquisition and cataloging of pharmacokinetic data and comprehensive information resources, (2) adapting efficient mechanisms for information delivery and outreach to target audiences and (3) utilizing complex quantitative tools and models for accurately estimating safe withdrawal intervals for a wide array of drugs and chemicals in nearly all species of domestic food animals. One of the major responsibilities of FARAD at UF is the development, maintenance and support of web-based and other electronic resources. Use of these resources has increased annually over the last decade, including over the past year, providing objective evidence of FARAD's strong, long-term growth. In the absence of FARAD and the program's well-recognized ability to provide scientifically-based recommendations for withdrawal intervals, extralabel drug use could not safely take place in food animal species. Specific objectives and accomplishments: The UF FARAD team continued to work with our collaborating institutions to validate computational estimates of safe withdrawal times. Our other major focus at the UF FARAD center during the reporting period remained support, maintenance and development of web-based and mobile-device resources. Use of all FARAD program services continue to grow, both in terms of the number of visits to our web-based information resources located at www.farad.org, and in the number of residue-related questions received via our telephone hotline and internet-based portal. During 2023 the regional access centers answered 5,825 specific inquiries (entailing multiple drugs/contaminants) that directly involved 5.8 million animals, representing a 33% increase over the previous year. Additionally, use of web-based resources, which are supported and maintained by the UF FARAD component, continued to increase dramatically. In this reporting period, in addition to supporting the other FARAD centers in achieving our common goals, UF FARAD continued to: • Maintain and upgrade web-based resources (available at www.farad.org) • Maintain and upgrade the VetGRAM apps for mobile devices for both Android and iOS users. • Perform frequent reviews of data on the FDA website, extract and new data on drug use in food animal species, and enter that information into the US Approved Animal Drugs Database (US-AADD). The database is essential to web-based and responder services, and it is vital that it be updated frequently so that information provided to users is current. We also continued to revise and expand the drug withdrawal databases that support our proprietary online withdrawal interval lookup tool, an online resource that allows access to recommended withdrawal intervals for selected drug-species combinations without the veterinarian having to submit a specific request through the online web portal. • The UF Center helped analyze pharmacokinetic data generated from other Regional Centers and provided other pharmacokinetic support as needed, including supporting the other FARAD centers to validate computational estimates of safe withdrawal times. • UF FARAD continued to develop PBPK models and user-friendly web-based interactive PBPK interfaces for use by FARAD responders for estimating withdrawal intervals of drugs, including further work on withdrawal intervals after the use of meloxicam in broiler chickens and laying hens, and florfenicol in sheep and goats. These projects are important as FARAD receives thousands of calls every year and it is imperative to provide timely and quality responses based on user-friendly scientific tools. We continued work on new machine learning and artificial intelligence models, including novel models to predict plasma half-lives of drugs in veterinary species, and presented this work at relevant national and regional meetings. Lastly, we developed a unique interactive, generic physiologically-based pharmacokinetic (igPBPK) model to estimate depletion of per- and polyfluoralkyl substances (PFAS) in cattle following requests for help from industry personnel on this topic; results have been published and the model is publicly available online (https://pbpk.shinyapps.io/igPFAS_PBPK/).
Publications
- Type:
Journal Articles
Status:
Published
Year Published:
2023
Citation:
Wu X, Lin Z, Toney E, Clapham MO, Wetzlich SE, Davis JL, Chen Q, Tell LA. Pharmacokinetics, tissue residue depletion, and withdrawal interval estimations of florfenicol in goats following repeated subcutaneous administrations. Food Chem Toxicol 181:114098. doi: 10.1016/j.fct.2023.114098, 2023.
- Type:
Journal Articles
Status:
Published
Year Published:
2023
Citation:
Chou WC, Tel LA, Baynes RE, Davis JL, Cheng YH, Maunsell FP, Riviere JE, Lin Z. Development and application of an interactive generic physiologically based pharmacokinetic (igPBPK) model for adult beef cattle and lactating dairy cows to estimate tissue distribution and edible tissue and milk withdrawal intervals for per- and polyfluoroalkyl substances (PFAS). Food Chem Toxicol 181:114062. doi: 10.1016/j.fct.2023.114062, 2023.
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2023
Citation:
Wu X. Utilizing artificial intelligence based quantitative structure-activity relationship (AI-QSAR) models to predict the plasma half-life or drugs in dogs. The Society of Toxicology Southeastern Regional Chapter (SESOT) meeting. (November 17, 2023).
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2023
Citation:
Wu PY. Predicting the plasma half-life of drugs in food animals with machine learning and artificial intelligence in quantitative structure-activity relationship modelling. The Society of Toxicology Southeastern Regional Chapter (SESOT) meeting (November 17, 2023).
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2023
Citation:
Ramachandran RA, Zad N, Tell LA, Xu X, Riviere JE, Baynes R, Lin Z, Maunsell F, Davis J, Jaberi-Douraki M. Harnessing Machine Learning for Veterinary Medicine Maximum Residue Limit Estimation. Poster Session, K-State AI Symposium (October 16th 2023).
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Progress 09/01/22 to 08/31/23
Outputs
Target Audience:The target audience for FARAD includes veterinarians, extension specialists, government and industry regulators as well as producers throughout all parts of the food animal industries. Veterinarians may submit questions for expert mediated consultations by FARAD via a nationwide toll-free hotline (1.888.USFARAD or 1.888.873.2723) or through an internet based online submission portal. The data bank, which is updated and maintained regularly, is readily searchable and allows for curated information to be accessed and considered by trained FARAD experts who provide guidance in response to inquiries from veterinarians about potential residue problems associated with situations involving contaminant exposure or legal extralabel drug therapy in food producing animal species. In addition, online and mobile-friendly apps (VetGRAM) provide access to a database of FDA-approved drug uses in animals. Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided?
Nothing Reported
How have the results been disseminated to communities of interest?The web-based resources developed and maintained by UF FARAD are readily available to the public through our free public websites. We also work on a daily basis with collaborating institutions to compile and update the data bank that is utilized by trained FARAD experts to provide guidance in response to inquiries from veterinarians regarding potential residue issues associated with contaminant exposure or legal extralabel drug use in food producing species. Papers were published in peer reviewed journals to disseminate FARAD-generated data to target audiences in the veterinary and scientific communities. Outreach by UF FARAD was conducted to Florida food animal veterinarians through a booth at the American Association of Bovine Practitioners annual conference in 2022. What do you plan to do during the next reporting period to accomplish the goals?The project is now in a no cost extension phase and during this we will complete the remaining project goals. We will continue to maintain and upgrade FARAD web-based services, maintain the central database of FDA-approved drugs, and contribute to the national FARAD objectives in collaboration with the other FARAD centers. There were several delays to work on the 2022 grant due to delays in Visa processing and recruitment for incoming PhD and Postdoctoral students, as well as some COVID-19-pandemic associated delays in website and software development in Dr. Maunsell's program in 2021 that had repercussions for work in 2022. Work will continue on to complete the project goal of development and publication of a physiologically-based pharmacokinetic (PBPK) model of florfenicol in small ruminants, and on conversion of developed phamacologic models into user-friendly web-based interfaces so that the FARAD responders can use these interfaces to predict withdrawal intervals. We will also continue our work on a generic interactive physiologically-based pharmacokinetic (PBPK) platform that allows FARAD responders to run simulations and predict withdrawal intervals for different drugs efficiently and rapidly. These projects are important, as FARAD receives thousands of calls a year, and it is imperative to provide timely and quality responses based on user-friendly scientific tools.
Impacts
What was accomplished under these goals?
Impact: The Food Animal Residue Avoidance Databank (FARAD) is a collaborative university-based food safety program that is coordinated and delivered by veterinary faculty and staff at several US colleges of veterinary medicine. Throughout its 41- year existence, FARAD has continued to evolve to meet the changing demands of providing accurate, timely and reliable service to both the veterinary profession and food animal industry stakeholders. At present, the program is managed through a very close collaboration of personnel at the University of California-Davis (UCD), University of Florida (UF), North Carolina State University (NCSU), Kansas State University-Olathe (KSUO) and Virginia-Maryland (VM) Colleges of Veterinary Medicine. The core mission of FARAD is to protect the American public by promoting the production of safe, animal-derived human food products (milk, eggs, meat, honey, etc.) that are devoid of violative or potentially unsafe chemical residues, including drugs, pesticides, environmental contaminants, natural toxins and other harmful substances. In order to carry out this mission, the FARAD team collates, analyzes and interprets the most up-to-date information and uses that unique data repository to provide accurate and timely expert advice to assist veterinarians who are faced with situations that could cause unsafe chemical residues in human food products. In addition, FARAD maintains and provides an array of complete information resources for veterinarians, extension specialists, farmers, regulatory personnel and others who are the stewards of our nation's expansive commercial food animal industries and the growing number of small backyard livestock operations. Beyond those primary functions, FARAD has a secondary impact on the food consuming public and contributes significantly to human public health and consumer confidence by providing food animal specialists with the most up-to-date and comprehensive scientific information available today. Throughout more than three decades of delivering this program, FARAD has continued to develop increased sophistication with respect to (1) acquisition and cataloging of pharmacokinetic data and comprehensive information resources, (2) adapting efficient mechanisms for information delivery and outreach to target audiences and (3) utilizing complex quantitative tools and models for accurately estimating safe withdrawal intervals for a wide array of drugs and chemicals in nearly all species of domestic food animals. One of the major responsibilities of FARAD at UF is the development, maintenance and support of web-based and other electronic resources. Use of these resources remains strong and has increased remarkedly over the past decade, providing objective evidence of FARAD's strong, long-term growth. In the absence of FARAD and the program's well-recognized ability to provide scientifically-based recommendations for withdrawal intervals, extralabel drug use could not safely take place in food animal species. Specific objectives and accomplishments: The University of Florida FARAD team continued to work with our collaborating institutions to validate computational estimates of safe withdrawal times. Our other major focus at the UF FARAD center during the reporting period remained support, maintenance and development of web-based and mobile-device resources. Use of all FARAD program services remains strong, both in terms of the number of visits to our web-based information resources located at www.farad.org, and in the number of residue-related questions received via our telephone hotline and internet-based portal. During 2022 the regional access centers answered 4,372 specific inquiries (entailing multiple drugs/contaminants) that directly involved approximately 3.5 million animals. Additionally, use of web-based resources, which are supported and maintained by the UF FARAD component, remained strong. In this reporting period, in addition to supporting the other FARAD centers in acheiving our common goals, UF FARAD continued to: Maintain and upgrade web-based resources (available at www.farad.org) Maintain and upgrade the VetGRAM apps for mobile devices Perform frequent reviews of data on the FDA website, extract and new data on drug use in food animal species, and enter that information into the US Approved Animal Drugs Database (US-AADD). The database is essential to web-based and responder services, and it is vital that it be updated frequently so that information provided to users is current. We also continued to revise and expand the drug withdrawal databases that support our proprietary online withdrawal interval lookup tool, an online resource that allows access to recommended withdrawal intervals for selected drug-species combinations without the veterinarian having to submit a specific request through the online web portal. Develop physiolgically-based pharmacokinetic (PBPK) models for various drugs in food animal species for withdrawal estimations; this included completion of PBPK models for meloxicam in broiler chickens and laying hens, and for flunixin in cattle and swine after dermal exposure, as well as development of a PBPK model for florfenicol in sheep and goats (nearing completion). Develop user-friendly web-based interactive PBPK platforms from previously developed PBPK models of oxytetracycline and procaine penicillin G in various food animal species; these models are accessible to FARAD responders and improve the process of calculation of withdrawal intervals following extralabel drug use. Continue work on a generic interactive PBPK platform, including use of this platform to predict meat and milk withdrawal intervals for per- and poly-fluoroalkyl substances (PFAS) in cattle. Work with other FARAD centers to develop new machine learning and artificial intelligence models that can predict withdrawal intervals of different drugs in different species. Conduct outreach at state and national (AABP, Society of Toxicology) meetings, as well as publish the developed models as described above.
Publications
- Type:
Journal Articles
Status:
Published
Year Published:
2023
Citation:
Zad N, Tell LA, Ramachandran RA, Xu X, Riviere JE, Baynes R, Lin Z, Maunsell F, Davis J, Jaberi-Douraki M. Development of machine learning algorithms to estimate maximum residue limits for veterinary medicines. Food Chem Toxicol. 2023, 179:113920. doi:10.1016/j.fct.2023.11920.
- Type:
Conference Papers and Presentations
Status:
Other
Year Published:
2022
Citation:
Lin, Z. An interactive physiologically based pharmacokinetic modeling platform to predict meat and milk residues and withdrawal intervals for perfluorooctanic acid, foerfluorooctane sulfonate and perfluorohexane sulfonate in beef and dairy cattle. Society for Risk Analysis (SRA) Annual Meeting, Tampa, FL, Dec 4-8, 2022.
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2023
Citation:
Chou WC. A web-based interactive generic physiologically based pharmacokinetic (igPBPK) platform and its application to predict meat and milk residues and withdrawal intervals for per- and poly-fluroalkyl substances (PFAS) in beef and dairy cattle. The 62nd Annual Meeting of Society of Toxicology, Nashville, TN. The Toxicologist, Supplement to Toxicological Sciences, 192 (S1), p. 413, abstract #: 4379, March 19-23, 2023.
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2023
Citation:
Wu X. Development of a physiologically based pharmacokinetic (PBPK) model for flunixin in cattle and swine following dermal exposure. The 62nd Annual Meeting of Society of Toxicology, Nashville, TN. The Toxicologist, Supplement to Toxicological Sciences, 192 (S1), p. 400, abstract #: 4325, March 19-23, 2023. [2023 Society of Toxicology Biological Modeling Specialty Section Best Trainee Abstract Award (Honorable Mention)]
- Type:
Journal Articles
Status:
Published
Year Published:
2023
Citation:
Chou WC, Lin Z. Machine learning and artificial intelligence in physiologically based pharmacokinetic modeling. Toxicol Sci, 2023; 191, 1-14, doi: 10.1093/toxsci/kfac101
- Type:
Journal Articles
Status:
Published
Year Published:
2022
Citation:
WC Chou, LA Tell, RE Baynes, JL Davis, FP Maunsell, JE Riviere, Z Lin. An interactive Generic Physiologically Based Pharmacokinetic (igPBPK) Modelling Platform to Predict Drug Withdrawal Intervals in Swine and Cattle: A Case Study on Flunixin, Florfenicol and Penicillin G. Toxicological Sciences. 2022;188(2):180-197. doi: 10.1093/toxsci/kfac056.
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