INTRODUCTION TO TOXICOLOGY

SIDNEY GREEN, PH.D.SIDNEY GREEN, PH.D.

DEPARTMENT OF PHARMACOLOGYDEPARTMENT OF PHARMACOLOGY

COLLEGE OF MEDICINECOLLEGE OF MEDICINE

HOWARD UNIVERISTYHOWARD UNIVERISTY

INTRODUCTION TO TOXICOLOGY

Definition of ToxicologyDefinition of Toxicology

- the basic science of poisons - the basic science of poisons (old)(old)

- the study of the adverse effects of - the study of the adverse effects of

chemical agents on biological systems chemical agents on biological systems

(new)(new)

INTRODUCTION TO TOXICOLOGY

WHAT TOXICOLOGISTS DOWHAT TOXICOLOGISTS DO -involved in the recognition, identification,-involved in the recognition, identification, and quantitation of hazardand quantitation of hazard -develops standards and regulations to -develops standards and regulations to protect health and the environmentprotect health and the environment - involved in safety assessment and use of- involved in safety assessment and use of data as basis for regulatory control of hazardsdata as basis for regulatory control of hazards - determines risk associated with use of chemicals - determines risk associated with use of chemicals

INTRODUCTION TO TOXICOLOGY

RISK ASSESSMENTRISK ASSESSMENT - Hazard identificationHazard identification- Dose Response AssessmentDose Response Assessment- Exposure AssessmentExposure Assessment- Risk CharacterizationRisk Characterization

INTRODUCTION TO TOXICOLOGY

INTERRELATED COMPONENTS OFINTERRELATED COMPONENTS OF

THE RISK ASSESSMENTTHE RISK ASSESSMENT- chemical or physical agentchemical or physical agent- biological systembiological system- effect or responseeffect or response- exposure situationexposure situation

INTRODUCTION TO TOXICOLOGY

AREAS OF TOXICOLOGY (FIELDS OFAREAS OF TOXICOLOGY (FIELDS OF

SPECIALTY)SPECIALTY)

-descriptive -environmental-descriptive -environmental

-mechanistic-mechanistic

-regulatory-regulatory

-forensic-forensic

-clinical-clinical

INTRODUCTION TO TOXICOLOGY

RISK AND SAFETYRISK AND SAFETY

--RISK;RISK; the probability that harm will occur the probability that harm will occur

under specified conditionsunder specified conditions

--SAFETYSAFETY; the probability that harm will not; the probability that harm will not

occur under specified conditionsoccur under specified conditions

INTRODUCTION TO TOXICOLOGY

FACTORS CONSIDERED IN FACTORS CONSIDERED IN DETERMINING ACCEPTABLE RISKDETERMINING ACCEPTABLE RISK

- benefitsbenefits- availability of substitutesavailability of substitutes- anticipated public useanticipated public use- employment considerationsemployment considerations- economic considerationseconomic considerations

INTRODUCTION TO TOXICOLOGY

FACTORS CONSIDERED IN FACTORS CONSIDERED IN DETERMINING ACCEPTABLE RISKDETERMINING ACCEPTABLE RISK

- effects on environmental qualityeffects on environmental quality- conservation of natural resourcesconservation of natural resources

INTRODUCTION TO TOXICOLOGY

MAJOR FACTORS THAT INFLUENCEMAJOR FACTORS THAT INFLUENCE

TOXICITYTOXICITY

-route of administration-route of administration

-duration and frequency of exposure-duration and frequency of exposure

-dose or concentration-dose or concentration

INTRODUCTION TO TOXICOLOGY

RAPIDITY OF RESPONSE WITH RAPIDITY OF RESPONSE WITH RESPECT TO ROUTE OF EXPOSURERESPECT TO ROUTE OF EXPOSURE

-intravenous -intradermal-intravenous -intradermal

-inhalation -topical -inhalation -topical

-intraperitoneally-intraperitoneally

-subcutaneous-subcutaneous

-intramuscular-intramuscular

INTRODUCTION TO TOXICOLOGY

SPECTRUM OF UNDERSIRED EFFECTSSPECTRUM OF UNDERSIRED EFFECTS

-allergic reactions-allergic reactions

-chemical allergies-chemical allergies

-idiosyncratic reactions-idiosyncratic reactions

-immediate vs. delayed toxicity-immediate vs. delayed toxicity

-reversible vs. irreversible toxicity-reversible vs. irreversible toxicity

-local vs. systemic toxicity-local vs. systemic toxicity

INTRODUCTION TO TOXICOLOGY

INTERACTION OF CHEMICALSINTERACTION OF CHEMICALS- AdditiveAdditive- SynergisticSynergistic- PotentiationPotentiation- Antagonism ( functional, chemical,Antagonism ( functional, chemical,

dispositional, receptor)dispositional, receptor)

INTRODUCTION TO TOXICOLOGY

TOLERANCETOLERANCE- state of decreased responsiveness to a toxicstate of decreased responsiveness to a toxic

effect of a chemical, resulting from previous effect of a chemical, resulting from previous exposureexposure

--dispositional tolerancedispositional tolerance; a decreased amount; a decreased amount

of drug reaching the siteof drug reaching the site

--cellularcellular; reduced responsiveness of a tissue; reduced responsiveness of a tissue

INTRODUCTION TO TOXICOLOGY

DOSE RESPONSEDOSE RESPONSE

--ASSUMPTIONSASSUMPTIONS

-response is due to chemical administered-response is due to chemical administered

-the response is related to the dose-the response is related to the dose

-there is a receptor site with which the-there is a receptor site with which the

chemical interactschemical interacts

INTRODUCTION TO TOXICOLOGY

DOSE RESPONSEDOSE RESPONSE

-ASSUMPTIONS (contd)-ASSUMPTIONS (contd)

-the degree of response is related to-the degree of response is related to

the concentration at the sitethe concentration at the site

-the concentration at the site is related-the concentration at the site is related

to the dose administeredto the dose administered

-has a quantifiable method of measuring and a -has a quantifiable method of measuring and a

precise means of expressing the toxicityprecise means of expressing the toxicity