Source: NORTH CAROLINA STATE UNIV submitted to
FOOD ANIMAL RESIDUE AVOIDANCE DEPLETION PROGRAM 2016-2017
Sponsoring Institution
National Institute of Food and Agriculture
Project Status
TERMINATED
Funding Source
OTHER GRANTS
Reporting Frequency
Annual
Accession No.
1010351
Grant No.
2016-41480-25728
Project No.
NCV-VMCG-0054
Proposal No.
2016-07554
Multistate No.
(N/A)
Program Code
FARAD
Project Start Date
Sep 1, 2016
Project End Date
Aug 31, 2018
Grant Year
2016
Project Director
Baynes, R.
Recipient Organization
NORTH CAROLINA STATE UNIV
COLLEGE OF VETERINARY MEDICINE
RALEIGH,NC 27606
Performing Department
Population Health & Pathobiolo
Non Technical Summary
The Food Animal Residue Avoidance Databank (FARAD) program is a chemical food safety program that has been in existence for more than 30 years. This has been a collaborative effort by scientists from four veterinary colleges at North Carolina State University, University of California Davis, University of Florida, and Kansas State University. The program goal 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 program accomplishes this through its objectives which are to identify, extract, assemble, evaluate and distribute reviewed information about residue avoidance and mitigation to persons such as veterinarians, extension agents, and regulatory scientists involved in residue avoidance programs throughout the United States. Each of the four FARD centers has expertise for delivery of the required information which eliminates redundancies and allows for smooth collaboration of collective talents unique to the field of veterinary pharmacokinetics research and related database management. The primary role of FARAD at NCSU is to respond to drug residue cases in livestock from food animal veterinarians and extension specialist and to provide research support that attempts to validate estimated withdrawal intervals following extralabel drug use. The latter is the primary reason why FARAD is utilized in drug residue cases.
Animal Health Component
100%
Research Effort Categories
Basic
0%
Applied
100%
Developmental
0%
Classification

Knowledge Area (KA)Subject of Investigation (SOI)Field of Science (FOS)Percent
7113440118020%
7113499118050%
7113599118010%
7113299118010%
7113820118010%
Knowledge Area
711 - Ensure Food Products Free of Harmful Chemicals, Including Residues from Agricultural and Other Sources;

Subject Of Investigation
3499 - Dairy cattle, general/other; 3299 - Poultry, general/other; 3820 - Goats, meat, and mohair; 3440 - Meat, dairy cattle; 3599 - Swine, general/other;

Field Of Science
1180 - Pharmacology;
Goals / Objectives
The primary goal of FARAD is 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.It accomplishes this through its objectives which are to identify, extract, assemble, evaluate and distribute reviewed information about residue avoidance and mitigation to people involved in residue avoidance programs throughout the United States.The types of information available through FARAD include basic veterinary drug registration information, withdrawal times, indications for use, as well as complex technical information about the pharmacokinetics and toxicokinetics of drugs and chemicals in food animals. In essence, FARAD serves as the primary source for scientifically-based recommendations for safe withdrawal intervals of drugs and chemicals in food producing animals. FARAD scientists protect the public health by averting food safety crises while ensuring that producers are not forced to cull food animals or dispose of meat, milk, and eggs that are much needed for the U.S. food supply. FARAD also supports agricultural producers who wish to export animal-derived food products through its development of a Global Veterinary Drug Database which contains extended drug withdrawal times that help producers meet export requirements.
Project Methods
The primary focus of the North Carolina FARAD component for 2016 - 2017 is two-fold: (1) collaborate with KSU, UC Davis, University of Florida, North Dakota State University, and ARS in Fargo, ND to validate many of our computational estimates of a safe withdrawal time and (2) to provide hot-line assistance by answering telephone inquiries in conjunction with UC-Davis and KSU.(1) Validation of the above PopPK and PBPK models to predict safe withdrawal times The focus for 2016-2017 is to continue to assess the influence of disease processes (e.g., respiratory disease in dairy calves) on clearance of danofloxacin and tulathromycin. Under the leadership of our Dr. Smith and our graduate student in the farad program, NCSU Farad will be conducting a population-based study (neonatal and ruminating calves) to assess the effects of infected calves on the tissue distribution and elimination kinetics of these two drugs widely used in treating pneumonia in cattle. This project is very important as neonatal calves continue to be a major source of drug residues and many livestock owners continue to use drugs extralabely in this class of animals as there are very few drugs approved for use in animals in this age group. The NCSU group is also exploring the PK of transdermal administration of flunixin and meloxicam in cattle and pigs using various in vitro and in vivo models. The residue kinetics of many of these NSAID applications are not known but are sometimes used in livestock.(2) Provide hot-line assistance by answering telephone inquiries in conjunction with UC-DavisWe will continue in conjunction with UC-Davis and KSU to answer residue avoidance inquiries received either by telephone or webmail requests. This service will be led by Dr. Jennifer Davis. We continue to look for appropriately trained post-DVM pharmacology students to give them the opportunity to work on the FARAD hot line. Faculty will also be involved when needed. However, the current yearly funding structure of FARAD severely restricts our ability to hire appropriate post-DVM graduate students and residents specifically for FARAD as sufficient funding is not available for the duration of their training or at the time when recruitment occurs. We will also continue to collaborate on writing timely FARAD Digests, collaborate on outreach programs, and coordinate activities with KSU, UC Davis and UF.

Progress 09/01/16 to 08/31/18

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 Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?Graduate students: Danielle Mzyk completed her PhD in pharmacokinetics and drug residue pharmacology in Fall 2017 and graduated in May 2018. She is currently in her final year of her DVM degree which was part of her dual DVM/PhD program with her research being conducted in our Center for Chemical Toxicology Research and Pharmacokinetics (CCTRP) where the NC FARAD program is housed. Dr.. Mzyk's research was been focused on the pharmacokinetics of select drugs in neonatal calves as very few drugs are approved for this age group and Bob veal calves continue to be a major source of drug residues at the national level. Because of her outstanding efforts in this regard, she has received several national awards 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. How have the results been disseminated to communities of interest?The results from this FARAD project have been disseminated in peer review publications as indicated in progress reports as well as at relevant livestock meetings and CE courses. Twelve (12) Journal articles published in 2016 - 2018 period and where NIFA support is acknowledged. 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. Emma Stafford, and our veterinary graduate students, Danielle Myzk and Andrew Fidler. Dr. Jennifer Davis at Virginia Tech who served as a sub-award from NCSU, also collaborated in providing timely responses to calls from veterinarians, and she interfaced with Drs. Geof Smith and Ronald Baynes especially with difficult risk management cases presented to the NCSU Farad office. All three faculty also actively interfaced with food animal veterinarians, managed the NCSU call center, validate 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. 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 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 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. User access to FARAD Resources during the previous two years REPORT PERIOD TOTAL INQUIRIES (Email + hotline) TOTAL WEBSITE VISITORS VetGRAM Page VISITS 2017 3,607 (+7.2%) 65,046 (+6.8%) 107,593 (+36.3%) 2016 3,366 (+10.5%) 60,904 (+20.9%) 78,937 (-30.4%) Numbers in parentheses indicate the percentage change relative to the previous year. Research activities: Our NC FARAD office has been conducting drug residue research that has focused on physiological factors that may result in violative residues even though the veterinarian and producer use the drugs in an approved manner. In this regard, we have examined the effects of age and disease on drug disposition of tulathromycin (Draxxin) in calves and danofloxacin in preruminant and ruminating calves. These have also resulted in several publications and abstract and oral presentations at national (AABP) and international meetings meetings such as the European Association of Veterinary Pharmacology and Toxicology Congress in Wroclaw, Poland in June 2018 and prior to that at the American Association of Veterinary Pharmacology and Therapeutics (AAVPT) Biennial Meeting in Potomac, MD, May 2017. Our team has also initiated several backyard poultry projects looking at plasma PK and drug residues in eggs. Our team started working with two consultants, Drs. Jason Chitterden and Jim Riviere in optimizing our population mixed effect modeling approaches to estimating safe withdrawal periods and also providing an interface that will allow our FARAD responders to use this computational tool in real time to provide more population based solutions to the residue cases we receive at our response center.

Publications


    Progress 09/01/16 to 08/31/17

    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 Changes/Problems:Dr. Jennifer Davis took a faculty position at Virginia Tech University in January 2017. Dr. Andrew Fidler joined the FARAD team in Spring 2017 and is in the process of completing his training of how to manage drug residue cases. What opportunities for training and professional development has the project provided?Graduate students: Danielle Mzyk has been a recipient of graduate training in pharmacokinetics and drug residue pharmacology. She is currently in the final year of her dual degree (DVM/PhD) program with her research being conducted in our Center for Chemical Toxicology Research and Pharmacokinetics (CCTRP) where the NC FARAD program is housed. Ms. Mzyk's research has been focused on the pharmacokinetics of select drugs in neonatal calves as very few drugs are approved for this age group and Bob veal calves continue to be a major source of drug residues at the national level. 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. 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?The NC component will continue to be involved in relevant research activities that has improved our understanding of drug residues in food animals so that we can better inform veterinarians and producers with this new knowledge. NC State will continue to conduct research with dairy calves of various ages to assess how physiological factors such as age and disease can influence the residue kinetics of drugs widely used in the livestock industry. NC State will continue 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.

    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, Kansas State 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, Co-PI, Dr. Jennifer Davis, and our veterinary graduate student, Danielle Myzk. Dr. Jennifer Davis worked with FARAD for the first 6 months of the grant in 2016 before taking a faculty position at Virginia Tech in January 2017. While she was at NCSU-CVM, she was primarily responsible for ensuring that the daily running of the response center and interfaces with Drs. Geof Smith and Ronald Baynes especially with difficult risk management cases presented to the NCSU Farad office. All three faculty also actively interface with food animal veterinarians, managed the NCSU call center, validate 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. 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 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 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. Research activities: Our NC FARAD office has been conducting drug residue research that has focused on physiological factors that may result in violative residues even though the veterinarian and producer use the drugs in an approved manner. In this regard, we have examined the effects of age and disease on drug disposition of tulathromycin (Draxxin) in calves and danofloxacin in preruminant and ruminating calves. These have also resulted in several publications and abstract and oral presentations at international (World Buiatrics Congress, Ireland July 2016 and AAVPT Biennial Meeting May 2017).

    Publications

    • Type: Journal Articles Status: Published Year Published: 2017 Citation: Mzyk, DA., Baynes, R.E., Martinez, M., Smith, G.W. (2017). Pharmacokinetics and distribution in interstitial and pulmonary epithelial lining fluid of 2 danofloxacin in ruminant and preruminant calves. J. Vet. Pharmacol. Therap. 40(2):179-191.
    • Type: Journal Articles Status: Published Year Published: 2017 Citation: Riviere, JE., Tell, L., Baynes RE., Vickroy, T., and Gehring, R. (2017). A User's Guide to FARAD resources: Historical and Future Perspectives. J. Am. Vet Med. Assoc. 250(10):1131-1139.
    • Type: Journal Articles Status: Published Year Published: 2017 Citation: Mzyk, D.A., Gehring R, , Tell, LA., Vickroy TW., Riviere JE., Ragan, G., Baynes RE. Smith, G. (2017). Considerations of extralabel drug use in calves J. Vet. Med Assoc. 250(11):1275-1282.
    • Type: Journal Articles Status: Published Year Published: 2017 Citation: Sidhu, P., Gehring R, , Mzyk, D.A., Marmulak, T., Tell, LA., Baynes RE, Vickroy TW., and Riviere JE. (2017). Avoiding violative flunixin meglumine residues in cattle and swine. J. Vet. Med Assoc. 250(2):182-189.
    • Type: Conference Papers and Presentations Status: Accepted Year Published: 2016 Citation: Myzk, D., Martinez, M., Baynes, RE., and Smith, G. (2016). Pharmacokinetics and distribution in interstitial and pulmonary epithelial lining fluid of danofloxacin in ruminant and preruminant calves. World Buiatrics Congress, Dublin, Ireland. July 2-9th., 2016
    • Type: Conference Papers and Presentations Status: Accepted Year Published: 2017 Citation: Mzyk, DA., Hobgood, GD., Messenger, KM., Martinez, M., Smith, G., Baynes, RE. (2017). The effect of age on the pharmacokinetics and distribution of tulathromycin in interstitial and pulmonary epithelial lining fluid in calves. AAVPT Biennial Meeting. Potomac, MD, May 21st  24th 2017