The Status of USDA Approval of Fenbendazole | Seminar 2012

Update on the Approval of Fenbendazole for Use in Pheasants


By Dr. Ron Griffith

Iowa State University

North Central Region Coordinator

Minor Use Animal Drug Program (NRSP-7)

 

I.  REVIEW OF REQUIREMENTS FOR DRUG APPROVALS

A. Good Clinical Practice (GCP) or Good Laboratory Practice GLP Studies

1. Efficacy

2. Target Animal Safety

3. Human Food Safety (Tissue Residue)

B. Environmental Impact Statement

C. Manufacturer Must Add Pheasants to the Label

D. Costs: Millions

E. Progress: Usually Slow

II. EFFICACY STUDY

A. Completed and accepted by the FDA/Center For Veterinary Medicine several years ago.

1.        Southern Region NRSP-7

2.    MacFarlane Pheasants

III. TARGET ANIMAL SAFETY

A. Completed at Iowa State in Summer 2011: Submission in 2012

1. 80 Male and 80 Female Pheasant Chicks

2. Fed 0, 100, 300 and 500 ppm FBZ for 21 days

3. Twice daily clinical evaluations

4. Feed Consumption

5. Necropsy

6. Histology

7. Clinical Pathology

i.      Serum chemistry

ii.     Complete blood counts

B. Results: No adverse effects at any dose level.

C. Reproductive Safety

1. Turkey Study: 1600 ppm FBZ

2. 3 years hatching data from MacFarlane=s

3. Does not appear to be an identifiable problem at 100 ppm FBZ

4. Will need a separate study if FDA/CVM doesn=t accept

IV. HUMAN FOOD SAFETY

A. Completed at ISU and UC-Davis in 2011: Submitted in 2012

B. Forty-two market-age birds

C. Fed 100 ppm for 7 days

D. Collected liver, breast muscle and thigh muscle

E. Tissues had to all be analyzed at U.C.-Davis within 1 week

F. Residues look to be within tolerances compared with turkey residues

G. Should have a 0-day withdrawal

TARGET ANIMAL SAFETY STUDY 

One-hundred sixty Chinese Ring-necked pheasants (Phasianus colchicus, 80 males and 80 females) were fed diets containing fenbendazole at 0, 100, 300 and 500 ppm for 21 days.  The birds were received at the Iowa State University Poultry Science Farm as 2-day-old chicks.  They were fed a commercial game bird starter ration containing no antibiotics, growth promotants or coccidiostats until Day 0 of the study (approximately 21 days of age).   At approximately 21 days of age, the birds were individually weighed, given health examinations, and placed on their respective study diets.  Four pens of males and four pens of females were placed in one of four blocks and within each block the pens were randomly assigned to receive one of the test diets. Day 0 was staggered for each of the 4 blocks to accommodate the necropsy and clinical pathology portions of the study so that birds were only on their test diets for 21 days.  Pheasants were fed each morning and clinical observations were recorded twice daily.  Feed consumption, feed conversion rate, body weights were determined. Three birds from each pen were randomly selected for necropsy, histopathology and clinical pathology.  Birds were carefully examined for feathering abnormalities immediately following euthanasia. There were no morbidities or mortalities.  There were no statistically significant and study-related differences in feed consumption, feed conversion rates, body weights, serum chemistry profiles, hematologic profiles, gross necropsy findings, histopathologic examination (only performed on 0 and 500 ppm treatment groups) and feathering. We were also required to determine reproductive safety of fenbendazole in adult birds.  There is only a single report in the literature indicating any reproductive problems with the feeding of fenbendazole.  That study was performed in male breeder turkeys which were fed an extremely high dose of fenbendazole (1600 ppm in feed for one week).  That dose was 100 times the recommended dose for turkeys.  There was a very dramatic but transitory decrease in fertility in the male breeder turkeys.  For this study, fertility and hatchability records were kept for several thousand breeder birds at MacFarlane Pheasant Farms in Janesville, WI for 2009, 2010 and 2011.  Groups of breeder pheasants were fed 100 ppm fenbendazole for 1 week intervals as needed for control of Heterakis gallinarum or Syngamus trachea.  Pheasants were treated only once or twice during the egg-laying season (approximately late March to July).  Fertility and hatchability are normally low at the start of the season, peak soon afterward and then decrease gradually over the summer months. There were no treatment related decreases in fertility or hatchability detected in any of the three breeding seasons. Based upon the studies outlined above, it appears that fenbendazole at 100 ppm in the feed is safe for pheasants.

HUMAN FOOD SAFETY STUDY

Thirty-two pheasants (16 males and 16 females) were placed on a diet containing 100 ppm fenbendazole for seven consecutive days.  A separate (control) group of 10 pheasants (5 males and 5 females) were maintained on a basal diet containing no fenbendazole.  Six, 12, 24 and 48 hours after removing the medicated feed, 8 fenbendazole treated pheasants (4 males and 4 females) and 2 control (1 male and 1 female) pheasants were randomly selected and euthanized for collection of the liver, pectoral muscle and thigh.  Tissues were analyzed for fenbendazole, fenbendazole sulfoxide and fenbendazole sulfone (marker residue).  These tissue data will be used by the Center for Veterinary Medicine, Human Food Safety reviewers to calculate an appropriate withdrawal time to insure the safety of edible pheasant tissues.  Quantifiable fenbendazole sulfone residues were detected in all tissues assayed at all time points.  The liver had the highest concentrations at the later time points, and is proposed as the target tissue for pheasants.  By 6 hours, liver concentrations of fenbendazole sulfone were below the turkey liver tolerance of 6 ppm and all muscle samples were below the turkey muscle tolerance of 2 ppm.  Based on these results, it is expected that the pheasant withdrawal time will be similar to the turkey withdrawal time of 0 days after oral treatment with fenbendazole.

About The Presenter

Dr. Griffith received his D.V.M. degree from Michigan State University in 1973, was in mixed practice in southern Michigan from 1973 until 1977 and was in an emergency clinic practice in 1981-82.  He moved to Iowa in 1977 and completed an MS in Veterinary Microbiology in 1980 and a Ph.D. in 1983.  He began teaching microbiology to veterinary students in 1979 and has been heavily involved in teaching to both veterinary and graduate students ever since.  His research has involved a variety of projects that included salmonella infection in swine, respiratory diseases in cattle and food safety in swine. He took over the coordinator position for the North Central Region, Minor Use Animal Drug Program (MUADP) in 2002.  Besides working with pheasants, he has had MUADP projects dealing with progesterone implants and antibiotics in sheep and goats, acaricides and antibiotics in cattle and even a project on antibiotic use in shrimp.  Dr. Griffith also has 300 acres that he has farmed himself since 1981 and a small flock of about 70 commercial ewes.  He also serves as a faculty advisor for the Student Chapter of the AVMA and the Small Ruminant Club at Iowa State.