Veterinary Toxicology: Current Veterinary Toxicology: Current and Futureand Future
Presented by:
L.D. Hopper, DVM, PhD, DABT
For:
Kansas State UniversityCollege of Veterinary Medicine
Nov 24, 2003
BackgroundBackground
DVM – KSU 1981DVM – KSU 1981 Private Practice – 1981-86Private Practice – 1981-86 PhD program – 1986-89PhD program – 1986-89 DABT - 1992DABT - 1992 Pharmaceutical Industry Toxicologist – Pharmaceutical Industry Toxicologist –
1989-20031989-2003
ExperienceExperience
Toxicologic evaluation of drugs, Toxicologic evaluation of drugs, metabolites, excipients, intermediatesmetabolites, excipients, intermediates
Risk assessments of substancesRisk assessments of substances Study designs, conduct, data evaluation Study designs, conduct, data evaluation
and report writingand report writing Toxicokinetic studiesToxicokinetic studies Pharmacologic studiesPharmacologic studies
Approach to this TopicApproach to this Topic
General topic with little specific published General topic with little specific published informationinformation
Personal perspective Personal perspective
Presentation of ideas and recognized Presentation of ideas and recognized opportunitiesopportunities
Current Veterinary ToxicologyCurrent Veterinary ToxicologyDemographicsDemographics
~67,000 AVMA member veterinarians~67,000 AVMA member veterinarians ~13,000 non-AVMA member veterinarians~13,000 non-AVMA member veterinarians ~45,000 AVMA members in private ~45,000 AVMA members in private
practicepractice 100 ABVT members100 ABVT members 170 active in Toxicology170 active in Toxicology
2003 AVMA Membership Directory
Veterinary Profession Demand Veterinary Profession Demand Projections by 2015 (%Growth)Projections by 2015 (%Growth)
Academia – 2%Academia – 2% Industry – 24%Industry – 24% Government – 2%Government – 2% Private Practice (SA) – 32%Private Practice (SA) – 32% Private Practice (LA) – 3%Private Practice (LA) – 3%
Are Pre-Veterinary and Veterinary Students being adequately informed of current and future needs?
JP Brown et al, JAVMA, 1999
Current and Future Market for Current and Future Market for VeterinariansVeterinarians
Falling real incomes, incomes lag behind Falling real incomes, incomes lag behind comparative professions, debt loadcomparative professions, debt load
Inability or unwillingness to consider working outside Inability or unwillingness to consider working outside traditional private practicetraditional private practice
Veterinarians did not feel prepared …., for Veterinarians did not feel prepared …., for employment outside private practice employment outside private practice
RE Lewis et al, JAVMA, 2003; JP Brown et al, JAVMA, 1999
Message?Message?
Demand will be high for veterinarians in Demand will be high for veterinarians in industryindustry
Private practice demand will be flat Private practice demand will be flat except for Small Animal clinicalexcept for Small Animal clinical
Financial security for many private Financial security for many private practitioners may not be sufficient for practitioners may not be sufficient for their input of time and moneytheir input of time and money
Are pre-veterinary and veterinary Are pre-veterinary and veterinary students being adequately informed of, students being adequately informed of, and prepared for, career opportunities?and prepared for, career opportunities?
Current Veterinary Toxicology:Current Veterinary Toxicology:Traditional Roles in AcademiaTraditional Roles in Academia
TeachingTeaching ServiceService ResearchResearch
Mirrors role of veterinary teaching hospitals
TeachingTeaching
Traditional clinical aspects of toxicology for Traditional clinical aspects of toxicology for practitioners – Core curriculum practitioners – Core curriculum
Training for post-DVM degrees and Training for post-DVM degrees and specialty certification specialty certification
Continuing EducationContinuing Education Research opportunities, promote the idea Research opportunities, promote the idea
of research as a career (not a product)of research as a career (not a product) Non-private practice awareness and Non-private practice awareness and
familiarization – familiarization – i.e.,i.e., industry, research industry, research
TeachingTeachingAt 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
Teaching - Areas of OpportunityTeaching - Areas of Opportunity
Internet applications for teaching and information Internet applications for teaching and information – – on-line courses, CEon-line courses, CE
Offering electives in non-traditional areas such Offering electives in non-traditional areas such
as regulatory toxicology, toxicogenomics, as regulatory toxicology, toxicogenomics, environmental toxicology, toxicologic pathologyenvironmental toxicology, toxicologic pathology
Emphasis on interdependence of veterinary, Emphasis on interdependence of veterinary, human, and ecological health – “human, and ecological health – “Veterinarians Veterinarians don’t just take care of pets and livestock”don’t just take care of pets and livestock”
Internet OpportunitiesInternet Opportunities
Teaching – clinical curriculum, continuing educationTeaching – clinical curriculum, continuing education Resource links – Resource links –
IVISIVIS VEINVEIN NOAHNOAH KSUCVM Toxicology Outreach?KSUCVM Toxicology Outreach?
Specific information, current topicsSpecific information, current topics Library/informationLibrary/information resources resources
ToxicogenomicsToxicogenomics Determination of expression levelsDetermination of expression levels Thousands of genes using DNA microarraysThousands of genes using DNA microarrays Up/down regulation patternsUp/down regulation patterns Characterize toxicants by class or by expression Characterize toxicants by class or by expression
patternspatterns Potential benefits: Genetic make-up, diagnosis, Potential benefits: Genetic make-up, diagnosis,
screening for early onset, prognosis, customize screening for early onset, prognosis, customize therapy, monitoring of progressiontherapy, monitoring of progression
The potential impact of toxicogenomics is just The potential impact of toxicogenomics is just beginning to be recognizedbeginning to be recognized
ML Cunningham et al, Toxicol Sci, 2003
ToxicogenomicsToxicogenomics
Resource/labor intensive Resource/labor intensive Massive data outputs to collate and Massive data outputs to collate and
evaluateevaluate Multi-disciplinary effortMulti-disciplinary effort Will be FDA driven Will be FDA driven
Food SafetyFood Safety
Genetically altered foodsGenetically altered foods Global food sourcesGlobal food sources Bioterrorism/BiosecurityBioterrorism/Biosecurity
EcotoxicologyEcotoxicology
Environment – multiple sources of toxic Environment – multiple sources of toxic contaminationcontamination
Public HealthPublic Health Sentinels – animals as targets or first effectorsSentinels – animals as targets or first effectors Toxicogenomics and environmental exposures Toxicogenomics and environmental exposures
Regulatory ToxicologyRegulatory Toxicology
Goals of Regulatory Toxicology studies – EPA, Goals of Regulatory Toxicology studies – EPA, FDA, ICHFDA, ICH
Approach to satisfying regulatory requirementsApproach to satisfying regulatory requirements Good Laboratory PracticesGood Laboratory Practices Animal models, numbersAnimal models, numbers Study endpointsStudy endpoints Study designs based on intended purpose of the Study designs based on intended purpose of the
study study
ServiceService
Diagnostic service – instrumentation and toxicogenomics
Referral cases - therapy Drug Testing Information resource – CE, internet
ResearchResearch 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
ConclusionsConclusions 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
Time’s Up?
AcknowledgementsAcknowledgements
My wife Mari, PhD, KSU 1989
For help with my Website
Study DesignStudy Design
5 daily doses PO in capsules5 daily doses PO in capsules 24 Beagle dogs – 3/sex/dose24 Beagle dogs – 3/sex/dose 3 dosage levels and control group3 dosage levels and control group Day 8 sac and day 60 sacDay 8 sac and day 60 sac Dosages derived from pilot studyDosages derived from pilot study
Study EndpointsStudy Endpoints
Body weight weeklyBody weight weekly Clinical observations dailyClinical observations daily Food consumption dailyFood consumption daily Hematology and Serum Chemistry days 8, Hematology and Serum Chemistry days 8,
15, 29 and 5815, 29 and 58 Plasma concentrations on days 1 and 5Plasma concentrations on days 1 and 5 Necropsy and microscopic pathologyNecropsy and microscopic pathology
Comparative Plasma ConcentrationsComparative Plasma ConcentrationsPO vs IVPO vs IV
107.8 103.8
456 495.9
0100200300400500600
Cmax AUC
ng/m
l (C
max
) or n
g*hr
/ml (
AU
C)
Oral (1 mg/kg) IV (0.9 mg/kg)
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