Progress 09/01/21 to 08/31/23
Outputs
Target Audience:NC FARAD currently works with food animal veterinarians, extension specialists, livestock farmers, and animal scientist in the management of drug and chemical residues in livestock animals. Dr. Baynes also represents FARAD as part the US delegation to Codex and participates in bi-monthly meetings; Dr. Foster sits on several AABP committees and has represented FARAD at AABP and by managing the FARAD booth at AABP meetings every September. Changes/Problems:NC FARAD successfully recruited two graduate students in 2020, Ranee Miller and Farha Sheela, who have been making steady progress in their graduate program. Dr. Geof Smith left the program in May 2021 to assume a position elsewhere and his responsibilities have been assigned to others in the NC FARAD program such as Dr. Jen Halleran and Dr. Derek Foster as they are also ruminant clinicians and very familiar as Dr. Smith with residue challenges facing food animal veterinarians. NC FARAD also recruited a postdoc in April 2021, Dr. Hiroko Enomoto. NC FARAD was also trying to recruit another postdoc to work on PopPK modeling. This was partially resolved with a sub-award to Kansas State University that recruited expertise but that too was delayed by 1 year. We have been able to recruit Earl Ford, who is conducting his PhD research in our laboratory with aim of better estimating meat and milk residues in dairy cattle exposed to antidote medication. These delays completing several animal studies and in recruiting personnel, were the primary reasons for the no-cost extension. This was finally resolved and the laboratory is fully functional. In January 2023, NC FARAD recruited Dr. Danielle Mzyk (DVM, PhD) from food animal private practice to assist with the increased call volume as well as the back log of projects that need to be completed. What opportunities for training and professional development has the project provided?Graduate students: During the reporting period (2021 to 2023), NC FARAD supported 4 graduate students and 1 postdoc. One graduate student, Emma Nixon, successfully defended her PhD thesis in August 2021 and all 4 papers from this thesis cited USDA FARAD support. Her research reported on the PK of 3 NSAIDs in pigs. She currently works for a pharmaceutical company because of her animal and PK expertise gleaned from working on FARAD. Dr. Jen Halleran successfully defended her thesis in November 2021 and is currently a tenured tract assistant professor in ruminant medicine at NCSU-CVM and is a collaborator on the FARAD grant. In 2020 we recruited two graduate students who were supported for most of the tw-year reporting period. Ranee Miller (Milk residues PK) and Farha Sheela (PopPK Modeling of drug residues in cattle) joined the NC FARAD team in 2020-2021 academic year as graduate students working on FARAD projects. Dr. Hiroko Enomoto joined the NC FARAD team in April 2021 as a postdoc to work on the sample analysis of several livestock drugs and PK modeling critical NC FARAD mission. The latter is already a first author or co-author on several publications (poultry residues) funded by this grant. A new graduate student from the NCSU Toxicology program, Earl Ford, joined the team in Jan 2023 and is working on a project pertaining to drug resides following the use of antidotal medication in cattle. This was a request from AABP as their veterinarians see that as a need. Undergraduate students: Several undergraduate students and veterinary students benefited from working in the residue laboratory during the summer and learnt how pharmacokinetic studies are conducted. One DVM student has gone into mixed practice; one DVM student is in her final year with focus on ruminant medicine another DVM student in her final year is focused on Public Health as a future career, one former undergraduate who spent one year in our pharmacology lab was influenced to apply to pharmacy school where she is now in her first year, and one undergraduate is applying to veterinary school next year to pursue mixed practice upon graduation. How have the results been disseminated to communities of interest?The results from this FARAD project have been disseminated in peer-review publications (see 16 publications and posters and oral presentations) as well at relevant livestock meetings and CE courses. What do you plan to do during the next reporting period to accomplish the goals?
Nothing Reported
Impacts
What was accomplished under these goals?
The program goals of FARAD is to provide the most updated information that result in the production of safe foods of animal origin through the prevention and mitigation of violative chemical (drug, pesticide, natural toxins, and environmental contaminant) residues in food animal products. The aim of this program is to maintain updated information on drug residues and related federal regulations as well as to help veterinarians and producers manage drug or chemical exposures in livestock that could result in violative residues in animal-derived food. This project therefore has an outreach component as well as research and training component. North Carolina State University FARAD continued to provide responses to residue avoidance inquiries. This was shared by the University of California, Virginia Tech University, and North Carolina State University FARAD staff. FARAD telephone and e-mail inquiries were answered on a weekly, rotating basis between the three sites. These services at NC FARAD were directed by the PI, Dr. Ronald Baynes, and his team of responders which included clinicians and veterinarians (graduate students, postdocs). During the last 2 years we also added Co-PIs, Dr. Jennifer Halleran, ruminant clinician along with Dr. Derek Foster and Dr. Kristen Messenger. All four faculty and responders actively interfaced with food animal veterinarians, managed the NCSU call center, and developed models and validated estimated withdrawal times from animal studies. All personnel were also actively involved in teaching drug residue avoidance principles to veterinary students, interns, residents, and graduate students. The NC FARAD component accomplished the following during the project period: Outreach activities: Our NC FARAD office provided technical expertise via phone calls (1-800-USFARAD) or via the internet and shares with responsibility with weekly rotations between NC FARAD, UC Davis, and Virginia Tech. Our FARAD responders at all three sites essentially screen the residues calls and the PIs supervise the responses. In very difficult cases (e.g., limited data set; possible carcinogens), all PIs across all 5 sites are involved as well as all responders. The table below is a summary of the growth of usage of several components of the FARAD program in the last two years. This often involved advising veterinarians and farmers on the best means to handle a drug residue case. FARAD may field as many as 70 calls a week and several times in 2023 we fielded slightly more than 100 calls per week. This means that sometimes as many as 15 - 20 cases per day and any given case may involve more than one livestock species or more than one drug or chemical exposure. Many of these cases were resolved within 24-48 hours, but complex chemical contaminant cases required more research and consultation and have taken close to 1 week to resolve. As backyard farming continues to grow in the US, (especially poultry in recent years), we see an increasing pattern of requests for guidance in these situations. NC FARAD faculty have made presentations as CE courses and manages educational booths on food animal residues and mitigation at the annual American Association of Bovine Practitioners (AABP) meetings amongst other meetings and workshops. In recent years at the request form AABP leadership on contentious issues. User access to FARAD Resources during the previous Two years USAGE REPORT PERIOD MEASURE 2022 2021 Inquiries to Regional Access Centers (hotline plus email) 4,372 (+19%) 4,465 Visit to 114,277 118,140 www.farad.org (+46%) VetGRAM Page 124,779 132,154 Visits In this submission, all data are adjusted to reflect the calendar year. Data on user access to FARAD resources are shown in the table above. Research activities: Our NC FARAD office has been conducting drug residue research that has focused on: (1) Development of PK models in cattle and swine, (2) Drug residues in poultry eggs and meat, (3) Drug residues in pigs associated with extralabel drug use of ponazuril, (4) flunixin drug residues in meat goats, and (5) milk residues studies in dairy cattle treated at different stages of the dry off period. These involved a significant amount of effort with recruitment of animals and space to conduct the residue studies as well as significant analytical method development for the analysis of these drugs in various tissues including milk and eggs. The data from our work adds to our database needs to help address the more pressing drug residue issues and challenges facing our food animal veterinarians and livestock producers. These research activities have also resulted in several publications and abstract and oral presentations at national (AABP) and the American Academy of Veterinary Pharmacology and Therapeutics Biennial meetings. Our FARAD program continues to be first stop on residues questions and drug residue policy issues from such organizations such as the AABP and AASV.
Publications
- Type:
Journal Articles
Status:
Published
Year Published:
2021
Citation:
Wang YS, Li M, Tell LA, Baynes RE, Davis JL, Vickroy TW, Riviere JE, Lin Z: Physiological parameter values for physiologically based pharmacokinetic models in food-producing animals. Part II: Chicken and turkey. J Vet Pharmacol Ther, 44(4):423-455, 2021. [PMID: 33289178]
- Type:
Journal Articles
Status:
Published
Year Published:
2021
Citation:
Smith LN, Bublitz D, Nixon E, Yeatts J, Ball RL, Baynes RE: Evaluation of the pharmacokinetic behavior of tulathromycin (Draxxin) in Florida manatees (Trichechus manatus latirostris) undergoing medical rehabilitation. J Zoo Wildl Med, 52(3):880-885, 2021.
- Type:
Journal Articles
Status:
Published
Year Published:
2022
Citation:
Lee, DF, Thompson, CL, Baynes, RE., Enomoto, H., Smith, GW., Chambers, MA. (2022). Development and evaluation of a bovine lung-on-chip (bLOC) to study bovine respiratory diseases. In Vitro Models 1(4-5):333-346.
- Type:
Journal Articles
Status:
Published
Year Published:
2023
Citation:
Petritz, OA., *Enomoto, H., Meyer, EG., Thomson, A., Baynes, RE., and Flammer, K. (2023). Pharmacokinetics and safety of sulfamethoxazole-trimethoprim after oral administration of single and multiple doses to Rhode Island Red chickens (Gallus gallus domesticus). J Avi Med Surg March 2023 Vol 37-1.
- Type:
Conference Papers and Presentations
Status:
Other
Year Published:
2022
Citation:
Rapid PBPK Model Parameterization for Estimating Food Animal Tissue Residues: Case Study Using ADMET Predictor and GastroPlus (Rob DeWoskin); The 61st Annual Meeting of Society of Toxicology, San Diego, CA. The Toxicologist, Supplement to Toxicological Sciences, 186, (S1), p. 305, abstract/poster board #: 4061/P760. (March 27-31, 2022)
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Progress 09/01/21 to 08/31/22
Outputs
Target Audience:NC FARAD currently works with food animal veterinarians, extension specialists, livestock farmers, and animal scientist in the management of drug and chemical residues in livestock animals. . Dr. Baynes also represents FARAD as part the US delegation to Codex and participates in bi-monthly meetings. Dr. Baynes was able to facilitate meetings with executive members of the AABP, AASV, and US FDA CVM on several technical residue challenges facing food animal veterinarians especially those working with the cattle and swine industry. Changes/Problems:Dr. Geof Smith resigned from NCSU-CVM in May 2021. We have had a new new graduate student, Farha Sheela, join in Jan 2021 and a new faculty member, Dr. Jennifer Hallera (DVM, PhD, ACVIM) joined the FARAD team in December 2021. One postdoctoral associate (Dr. Hiroko Enomoto, DVM) joined our team in April 15th 2021. What opportunities for training and professional development has the project provided?Graduate students: Emma Nixon completing her PhD in pharmacology in Fall 2021. Ranee Miller started her PhD in Fall 2020. Farha Sheela is a new graduate student who joined our team in January 2021. Dr. Jen Halleran (DVM) defended her PhD thesis in November 2021. . Undergraduate students: Several undergraduate students and veterinary students benefited from working in the residue laboratory during the summer and learnt how pharmacokinetic studies are conducted. One veterinary student, Emily Wiloch, recently completed a flunixin transdermal study in dairy goats that helped estimate w milk withdrawal interval. This was a first. Another veterinary student, Baxter Elliot, joined the FARAD group in May 2022 to work on a poultry PK and residue project. Two additional NCSU undergraduate students who will be applying to veterinary colleges and graduate school in pharmacology also joined to team in summer 2022 to work on a ruminant PK study with the flunixin drug that continues a target residue for US FSIS. How have the results been disseminated to communities of interest?The results from this FARAD project have been disseminated in peer-review publications as well at relevant livestock meetings and CE courses. What do you plan to do during the next reporting period to accomplish the goals?
Nothing Reported
Impacts
What was accomplished under these goals?
North Carolina State University continued to provide responses to FARAD residue avoidance inquiries. This was shared by the University of California, Virginia Tech University, and North Carolina State University FARAD staff. FARAD telephone and e-mail inquiries were answered on a weekly, rotating basis between the three sites. These services at NC were provided by the PI, Dr. Ronald Baynes, Dr. Geof Smith, Dr. Derek Foster, and Dr. Kristen Messenger, and our veterinary graduate students, Dr. Jen Halleran (DVM), Ms. Emma Nixon, Ms. Ranee Miller, and Ms. Farha Sheela. These individuals all collaborated in providing timely responses to calls from veterinarians. We all actively interfaced with food animal veterinarians, managed the NCSU call center, validated estimated withdrawal times, and teach residue avoidance principles to veterinary students, interns, residents, and graduate students. The NC FARAD component accomplished the following during the project period: Outreach activities: Our NC FARAD office provided technical expertise via phone calls (1-800-USFARAD) or via the internet and our activity in increased significantly since the 2020 period. This often involved advising veterinarians and farmers on the best means to handle a drug residue case in collaboration with FARAD centers at UC Davis and Virginia Tech. The FARAD program across the U.S. may field as many as 70 inquires a week and sometimes as many as 15 - 20 cases per day and any given case may involve more than one livestock species or more than one drug or chemical exposure. Many of these cases were resolved within 24-48 hours, but complex chemical contaminant cases required more research and consultation. There has been a growing interest in backyard farming (especially poultry in recent years) during the last reporting period and we received many requests for guidance in these situations. NC FARAD faculty have in the past made presentations as CE courses and manages educational booths on food animal residues and mitigation at the annual American Association of Bovine Practitioners (AABP) meetings amongst other meetings and workshops. The latter was limited during the Covid period since March 2020. In 2021 FARAD responded to a greater number of inquiries (a 13.7% increase) regarding residue avoidance in food-producing animals than in the previous year. In addition, as food animal industries struggled to adapt during the pandemic, FARAD assisted with COVID-19 related cases including providing withdrawal interval recommendations for milk diversion to animal feed, and repurposing of drugs needed for altered production lines. Tremendous use of the web-based resources at www.farad.org continued in 2021, with over 81,000 users making 118,140 visits ( users(daily average of 336 visits), representing a 79% increase over the past 5 years. Of these users, 57,457 (71%) originated from IP addresses located within the United States. The proportion of visitors originating from outside the US (29%) was similar to that observed in 2020. In total, website visits originated from an impressive total of 188 countries, with the top ten numbers of non-US visitors being from (high to low) Canada, United Kingdom, India, Australia, Philippines, China, Mexico, Ireland, Saint Kitts & Nevis, and Pakistan. A continued trend in 2021 was a high demand for the internet-based VetGRAM platform (375 visits per day). Other highly viewed pages on the FARAD website included the Withdrawal Interval (WDI) Recommendation Lookup, the Withdrawal Date Calculator, the Restricted and Prohibited Drugs page and the Extra-Label Drug Use information pages. Although most interaction with FARAD occurs via the modalities described above, FARAD users also followed us on Facebook and Twitter; a focus for 2022 of the UF FARAD program is increasing access to FARAD resources through social media platforms. User Access to FARAD Resources During the PAST Five Years Usage Measure REPORT PERIOD* 2021 2020 2019 2018 2017 Inquiries to Regional Access Centers (hotline plus email) 4,465 (+14%) 3,926 (+4%) 3,765 (+3%) 3,645 (+1%) 3,607 (+7%) Visit to www.farad.org 118,140 (-9%) 128,915 (+15%) 111,783 (+43%) 78,064 (+18%) 65,960 (+17%) VetGRAM Page Visits 132,154 (-5%) 139,690 (+9%) 128,644 (+4%) 124,186 (+22%) 102,083 (+18%) Data are presented as raw numbers with percent changes relative to the previous year in parentheses Research activities: Our NC FARAD office has been conducting drug residue research that has focused on various drugs and several species. Emma Nixon completed her PhD in pharmacology in August 2021 and she has generated 4 peer-review publications during her 4 yrs with our group. Her work has focused on pharmacokinetics and residue depletion of NSAIDs (flunixin, meloxicam, and ketoprofen) in piglets. This last year she published 2 papers on the topic. Jen Halleran is another graduate student who is currently analyzing data from her florfenicol study in steers. Ranee Miller started her PhD in Fall 2020 and is currently involved in a eprinomectin (LongRange) milk residue study in dry cows. Farha Sheela is another new graduate student who joined our team in January 2021 and her focus has been on using novel mathematical models to estimate meat and milk withdrawal intervals for drug residues in livestock. She has thus far developed a revised and much improved model for flunixin residues in cattle. Our veterinary student, Emily Wiloch, recently completed a flunixin transdermal study in dairy goats that helped estimate milk withdrawal interval. This was a first. Our postdoc, Hiroko Enomoto, successfully published a paper on drug residue depletion in eggs in laying hens for Bactrim. Our NC FARAD component also collaborated with the other FARAD personnel to produce several peer-reviewed review publications on physiological parameters that will be useful in developing our physiologically-based pharmacokinetic models used to estimate residue withdrawal intervals.
Publications
- Type:
Journal Articles
Status:
Published
Year Published:
2021
Citation:
Nixon, E., Chitterden, J., Baynes, RE., and Messenger. K. (2022) Pharmacokinetic/Pharmacodynamic Modeling of Ketoprofen and Flunixin at Piglet Castration and Tail-Docking. J. Vet. Pharmacol, Therap. doi: 10.1111/jvp.13083.
2. Yuan, L, Chou, W., Richards, ED., Tell, LA, Baynes, RE., Davis, JL., Maunsell, FP., Riviere, JE., Lin, Z., (2022). A Web-Based Interactive Physiologically Based Pharmacokinetic (iPBPK) Model for Meloxicam in Broiler Chickens and Laying Hens. J. Vet. Pharmacol. Therap. (in press).
3. Chou, W., Tell. L., Baynes, RE., Davis, J., Maunsell, F., Riviere, JE, and Lin, Z. (2022). An Interactive Generic Physiologically Based Pharmacokinetic (igPBPK) Modeling Platform to Predict Drug Withdrawal Intervals in Cattle and Swine: A Case Study on Flunixin, Florfenicol and Penicillin G. Toxicol. Sci. (in press).
4. *Halleran, J., Minch, R., Sylvester, H., Jacob, M., Prange, T., Baynes, RE., and Foster, D. (2021). Comparison of the gastrointestinal pharmacokinetics of two different florfenicol dosing regimens and its impact on the prevalence and phenotypic resistant of AMR E. coli and Enterococcus over time. Microorganisms doi: 10.3390/microorganisms9091835.
5. Meira, E., Wiloch, E., Nixon, E., Yeatts, JL., Sheela, F., Smith, GW., and Baynes, RE. (2021). The Pharmacokinetics of Transdermal Flunixin in Lactating Dairy Goat. J. Dairy Sci. 105(1):549-559.
6. Riad, M; Baynes, R.E., Tell, L; Davis, J; Maunsell, F; Riviere, J; Lin, Z (2021). Development and Application of an interactive Physiologically Based Pharmacokinetic (iPBPK) Model to Predict Oxytetracycline Tissue Distribution and Withdrawal Intervals in Market-Age Sheep and Goats. Toxicol Sci 183(2): 253-268.
- Type:
Journal Articles
Status:
Published
Year Published:
2021
Citation:
7. *Nixon, E., Carlson, AR., Routh, PA., Hernandez, L., Almond, G., Baynes, RE., Messenger, K. (2021). Comparative effects of nonsteroidal anti-inflammatory drugs at castration and tail-docking in neonatal piglets PLOS ONE 16(11): e0254409.
8. *Enomoto, H., Petritz, O., Thomson, A., Flammer, K., Ferdous; F., Meyer; E., Tell, L., and Baynes RE. (2021). Egg residue and depletion in Rhode Island Red hens (Gallus gallus domesticus) following multiple oral doses of Trimethoprim-Sulfamethoxazole. Regul. Pharmacol Toxicol. 123:104941.doi: 10.1016/j.yrtph.2021.104941.
9. Mercer, MA. Davis, JL, Riviere, JE., Baynes, RE., Tell, LA, Jaberi-Douraki, M., Maunsell, FP., and Lin, Z. (2021). Mechanisms of Toxicity and Residue Considerations of Rodenticide Exposure in Food Animals: a FARAD Perspective. J. Am. Vet Med. Assoc 260(5):514-523.
10. *Halleran, J., Papich, MG., Li, M., Lin, Z., Davis, J., Maunsell, F., Riviere, JE., Baynes, RE., and Foster, DM. (2021). Update on Withdrawal Interval for Extra Label Use of Procaine Penicillin G in Cattle and Swine. J. Am. Vet. Med. Assoc 260(1):50-55 .
11. Richards, ED., Tell, LA., Davis, JL, Baynes, RE., Lin, Z., Maunsell, FP., Riviere, JE., Davidson, G. (2021). Honey Bee Medicine for Veterinary Professionals-Avoiding Residues in Honey. J. Am. Vet. Med. Assoc 259(8): 860-873
12. Robles, I., Arruda, A., *Nixon, E., Johnstone, E., Wagner, B., Edwards-Callaway, L., Baynes, R., Coetzee, J., Pairis-Garcia, M. (2021). Producer and veterinarian perspectives towards pain management practices in the US cattle industry. Animals 11(1):209.doi: 10.3390/ani11010209.
13. Wagner, B., *Nixon, E., Robles, I., Baynes, RE., Coetzee, H., Pairis-Garcia, M (2021). Non-steroidal anti-inflammatory drugs: Pharmacokinetics and mitigation of procedural-pain in cattle. Animals Jan 22;11(2):282. doi: 10.3390/ani11020282
NCSU FARAD Abstracts and Poster Presentations :
NCSU FARAD personnel managed the AABP booth in Sept 2021 and although there were limited conference attendances because of the Covid pandemic, several personnel presented posters at the Annual SOT meeting in San Diego, CA in March 2022 and via zoom to various audiences such as AAVPT meeting in May 2022.
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