1. INTRODUCTION TO TOXICOLOGY SIDNEY GREEN, PH.D. DEPARTMENT OF PHARMACOLOGY COLLEGE OF MEDICINE HOWARD UNIVERISTY

2. INTRODUCTION TO TOXICOLOGY Definition of Toxicology Definition of Toxicology - the basic science of poisons (old) - the basic science of poisons (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)

3. INTRODUCTION TO TOXICOLOGY WHAT TOXICOLOGISTS DO WHAT TOXICOLOGISTS DO -involved in the recognition, identification, -involved in the recognition, identification, and quantitation of hazard and quantitation of hazard -develops standards and regulations to -develops standards and regulations to protect health and the environment protect 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 hazards data as basis for regulatory control of hazards - determines risk associated with use of chemicals - determines risk associated with use of chemicals

4. INTRODUCTION TO TOXICOLOGY RISK ASSESSMENT RISK ASSESSMENT - Hazard identification - Dose Response Assessment - Exposure Assessment - Risk Characterization

5. INTRODUCTION TO TOXICOLOGY INTERRELATED COMPONENTS OF INTERRELATED COMPONENTS OF THE RISK ASSESSMENT THE RISK ASSESSMENT - chemical or physical agent - biological system - effect or response - exposure situation

6. INTRODUCTION TO TOXICOLOGY AREAS OF TOXICOLOGY (FIELDS OF AREAS OF TOXICOLOGY (FIELDS OF SPECIALTY) SPECIALTY) -descriptive -environmental -mechanistic-regulatory-forensic-clinical

7. INTRODUCTION TO TOXICOLOGY RISK AND SAFETY RISK AND SAFETY -RISK; the probability that harm will occur under specified conditions under specified conditions -SAFETY; the probability that harm will not occur under specified conditions occur under specified conditions

8. INTRODUCTION TO TOXICOLOGY FACTORS CONSIDERED IN DETERMINING ACCEPTABLE RISK FACTORS CONSIDERED IN DETERMINING ACCEPTABLE RISK - benefits - availability of substitutes - anticipated public use - employment considerations - economic considerations

9. INTRODUCTION TO TOXICOLOGY FACTORS CONSIDERED IN DETERMINING ACCEPTABLE RISK FACTORS CONSIDERED IN DETERMINING ACCEPTABLE RISK - effects on environmental quality - conservation of natural resources

10. INTRODUCTION TO TOXICOLOGY MAJOR FACTORS THAT INFLUENCE MAJOR FACTORS THAT INFLUENCE TOXICITY TOXICITY -route of administration -duration and frequency of exposure -dose or concentration

11. INTRODUCTION TO TOXICOLOGY RAPIDITY OF RESPONSE WITH RESPECT TO ROUTE OF EXPOSURE RAPIDITY OF RESPONSE WITH RESPECT TO ROUTE OF EXPOSURE -intravenous -intradermal -inhalation -topical -intraperitoneally-subcutaneous-intramuscular

12. INTRODUCTION TO TOXICOLOGY SPECTRUM OF UNDERSIRED EFFECTS SPECTRUM OF UNDERSIRED EFFECTS -allergic reactions -chemical allergies -chemical allergies -idiosyncratic reactions -immediate vs. delayed toxicity -reversible vs. irreversible toxicity -local vs. systemic toxicity

13. INTRODUCTION TO TOXICOLOGY INTERACTION OF CHEMICALS INTERACTION OF CHEMICALS - Additive - Synergistic - Potentiation - Antagonism ( functional, chemical, dispositional, receptor) dispositional, receptor)

14. INTRODUCTION TO TOXICOLOGY TOLERANCE TOLERANCE - state of decreased responsiveness to a toxic effect of a chemical, resulting from previous exposure effect of a chemical, resulting from previous exposure -dispositional tolerance; a decreased amount -dispositional tolerance; a decreased amount of drug reaching the site of drug reaching the site -cellular; reduced responsiveness of a tissue -cellular; reduced responsiveness of a tissue

15. INTRODUCTION TO TOXICOLOGY DOSE RESPONSE DOSE RESPONSE -ASSUMPTIONS -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 interacts chemical interacts

16. INTRODUCTION TO TOXICOLOGY DOSE RESPONSE DOSE RESPONSE -ASSUMPTIONS (contd) -the degree of response is related to -the degree of response is related to the concentration at the site the concentration at the site -the concentration at the site is related -the concentration at the site is related to the dose administered to the dose administered -has a quantifiable method of measuring and a -has a quantifiable method of measuring and a precise means of expressing the toxicity precise means of expressing the toxicity