2. Veterinary Toxicology: Current and Future Presented by: L.D. Hopper, DVM, PhD, DABT For: Kansas State University College of Veterinary Medicine Nov 24, 2003

3. Background  DVM – KSU 1981  Private Practice – 1981-86  PhD program – 1986-89  DABT - 1992  Pharmaceutical Industry Toxicologist – 1989-2003

4. Experience  Toxicologic evaluation of drugs, metabolites, excipients, intermediates  Risk assessments of substances  Study designs, conduct, data evaluation and report writing  Toxicokinetic studies  Pharmacologic studies

5. Approach to this Topic  General topic with little specific published information  Personal perspective  Presentation of ideas and recognized opportunities

6. Current Veterinary Toxicology Demographics  ~67,000 AVMA member veterinarians  ~13,000 non-AVMA member veterinarians  ~45,000 AVMA members in private practice  100 ABVT members  170 active in Toxicology 2003 AVMA Membership Directory

7. Veterinary Profession Demand Projections by 2015 (%Growth)  Academia – 2%  Industry – 24%  Government – 2%  Private Practice (SA) – 32%  Private Practice (LA) – 3% Are Pre-Veterinary and Veterinary Students being adequately informed of current and future needs? JP Brown et al, JAVMA, 1999

8. Current and Future Market for Veterinarians  Falling real incomes, incomes lag behind comparative professions, debt load  Inability or unwillingness to consider working outside traditional private practice  Veterinarians did not feel prepared …., for employment outside private practice RE Lewis et al, JAVMA, 2003; JP Brown et al, JAVMA, 1999

9. Message?  Demand will be high for veterinarians in industry  Private practice demand will be flat except for Small Animal clinical  Financial security for many private practitioners may not be sufficient for their input of time and money  Are pre-veterinary and veterinary students being adequately informed of, and prepared for, career opportunities?

10. Current Veterinary Toxicology: Traditional Roles in Academia  Teaching  Service  Research Mirrors role of veterinary teaching hospitals

11. Teaching  Traditional clinical aspects of toxicology for practitioners – Core curriculum  Training for post-DVM degrees and specialty certification  Continuing Education  Research opportunities, promote the idea of research as a career (not a product)  Non-private practice awareness and familiarization – i.e., industry, research

12. Teaching At the initial level, efforts are needed to ensure that veterinary students are aware of these career opportunities early in their education. Potential strategies include offering externships and public health rotations, such as at CDC or at local and state health departments, as part of veterinary medical school training courses and offering combined degrees in veterinary medicine and public health (i.e., DVM/MPH)—a course of study already offered by several veterinary colleges. Other innovative public health programs that could be incorporated by veterinary medical colleges include studies in food safety, environmental toxicology, healthy ecosystems, international diseases, and population medicine. L King, Emerging Infectious Diseases, 2003

13. Teaching - Areas of Opportunity  Internet applications for teaching and information – on-line courses, CE on-line courses, CEon-line courses, CE  Offering electives in non-traditional areas such as regulatory toxicology, toxicogenomics, environmental toxicology, toxicologic pathology  Emphasis on interdependence of veterinary, human, and ecological health – “Veterinarians don’t just take care of pets and livestock”

14. Internet Opportunities  Teaching – clinical curriculum, continuing education  Resource links – IVIS IVIS IVIS VEIN VEIN VEIN NOAH NOAH NOAH KSUCVM Toxicology Outreach? KSUCVM Toxicology Outreach? KSUCVM Toxicology Outreach? KSUCVM Toxicology Outreach?  Specific information, current topics  Library/information resources Library/information

15. Toxicogenomics  Determination of expression levels  Thousands of genes using DNA microarrays  Up/down regulation patterns  Characterize toxicants by class or by expression patterns  Potential benefits: Genetic make-up, diagnosis, screening for early onset, prognosis, customize therapy, monitoring of progression  The potential impact of toxicogenomics is just beginning to be recognized ML Cunningham et al, Toxicol Sci, 2003

16. Toxicogenomics  Resource/labor intensive  Massive data outputs to collate and evaluate  Multi-disciplinary effort  Will be FDA driven

17. Food Safety  Genetically altered foods  Global food sources  Bioterrorism/Biosecurity

18. Ecotoxicology  Environment – multiple sources of toxic contamination  Public Health  Sentinels – animals as targets or first effectors  Toxicogenomics and environmental exposures

19. Regulatory Toxicology  Goals of Regulatory Toxicology studies – EPA, FDA, ICH  Approach to satisfying regulatory requirements  Good Laboratory Practices  Animal models, numbers  Study endpoints  Study designs based on intended purpose of the study

20. Service   Diagnostic service – instrumentation and toxicogenomics   Referral cases - therapy   Drug Testing   Information resource – CE, internet

21. Research   Driven by needs of practitioners, state/region   Must be compatible with faculty and institutional interests/expertise   External funding – need to provide useable product which may be outside the needs of practitioners and the state   Areas of need – Food safety, biosecurity/terrorism, environmental health, toxicogenomics and mechanisms

22. Conclusions   Continue Veterinary teaching role following recommended core curriculum   Increase exposure to and content of information about career opportunities outside traditional private clinical practice   Opportunities for utilizing the internet for teaching and information resources   Toxicogenomics is a wide open frontier for basic as well as applied research

23. Time’s Up?

24. Acknowledgements My wife Mari, PhD, KSU 1989 For help with my Website

25. Study Design  5 daily doses PO in capsules  24 Beagle dogs – 3/sex/dose  3 dosage levels and control group  Day 8 sac and day 60 sac  Dosages derived from pilot study

26. Study Endpoints  Body weight weekly  Clinical observations daily  Food consumption daily  Hematology and Serum Chemistry days 8, 15, 29 and 58  Plasma concentrations on days 1 and 5  Necropsy and microscopic pathology

27. Comparative Plasma Concentrations PO vs IV