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)