1. Identification of toxic substances, their biological effects ( 生物效应 ) and management of risk

2. Topics to be addressed Regulatory and health agencies Pre-market ( 上市前 ) toxicity evaluation Post-market evaluation of toxicity and biological effects

3. Responsible agencies on toxic substances 1.Regulatory agencies: EPA (Environmental Protection Agency), FDA (Food and Drug Administration). 3.Influenced by politics ( 政治 ), industries, and consumer ( 消费者 ) and legal groups 4.Which agency regulates cigarette smoking? 5.Any regulations on passive exposure to cigarette smoke?

4. Agencies and their valuable websites International Agency for Research on Cancer: www.iarc.fr;www.iarc.fr Environmental Protection Agency: www.epa.gov www.epa.gov Pubmed: www.ncbi.nlm.nih.gov

5. International Agency for Research on Cancer (IARC) Evaluate published data from human epidemiologic and animal studies Determine carcinogenic activities of chemicals, groups of chemicals, complex mixtures ( 混合物 ), occupational exposures, cultural habits, biological or physical agents

6. IARC classifications Group 1 – human carcinogens: asbestos, cigarette smoke chemicals, ionizing radiation Group 2A – Probable ( 很可能的 ) human carcinogens: acrylamide, adriamycin. Group 2B – Possible ( 可能的 ) human carcinogens: acetaldehyde, bleomycin, carbon tetrachloride Group 3 – Not classifiable as to carcinogenic to humans: acrylic fibers, caffeine Group 4 – Probably not carcinogenic to humans

7. USEPA: www.epa.gov Search : Main menu –Chemicals and ToxicsChemicals and Toxics –Climate ChangeClimate Change –EmergenciesEmergencies –Health and SafetyHealth and Safety –PesticidesPesticides –WasteWaste –Laws & Regulations, etc.Laws & Regulations

8. National Center for Biotechnology Information: www.ncbi.nlm.nih.gov Database of Genotypes and Phenotypes (dbGaP) Genetic Testing Registry Influenza Virus Online Mendelian Inheritance in Man (OMIM) PubMed PubMed Central (PMC) PubMed Clinical Queries All Genetics & Medicine Resources...

9. Identification of toxicity in consumer products Premarket testing using standardized protocols No premarket testing of natural and some other products (Dietary Supplements, e.g. Ginseng tablets) Postmarket monitoring of toxic effects in human populations or in experimental animals

10. Federal Regulations Toxicity: Testing for a Pesticide

11. Pharmaceutical drug testing In vitro testing for effectiveness ( 有效性 ) and toxicity, e.g. tumor cell lines, bacterial cultures Effectiveness study in animals Safety and efficacy test, especially in comparison with existing drugs Clinical trials in human – 3 phases: a small group of healthy volunteers, a large group of patients and controls, a very large group of patients (up to 10,000) About 1/5000 chemicals tested became an approved drug

12. Benefits and limitations of pre- market testing protocols Benefits: Standardized protocols ( 标准化 ) Comparison of toxicity Short duration to provide results Limitations: Use of standardized cell culture or animal Use of high doses Limited test endpoints Very limited testing on mixtures

13. Postmarket testing of products and medical activities

15. Population responses to exposure/therapy

16. Why do we conduct population studies 1.Identify exposure and assess health risk 2.Evaluate hazards based on reduced exposure conditions 3.Understand species and inter-individual differences 4.Identify toxicity from mixtures 5.Provide early warning signals for exposed populations somatic ( 体 ), germ 生殖 ) and embryonic ( 胚胎 ) cells ( 细胞 )

17. Characteristics of epidemiologic studies Provides the most useful information on health effects from specific exposure conditions Requires large sample sizes Insensitive to the detection of small effects Does not distinguish individual variations

18. Biomarkers of effect with clinical relevance Semen ( 精液 ) quality and sperm count Urinary hormone assays Pulmonary function test Immunoglobulin ( 免疫球蛋白 ) levels Blood lead ( 铅 ) and other chemicals

19. Biomarkers for subclinical disease 1.Serum alpha-fetoprotein for liver cancer and GI disease 2.Carcinoembryonic antigen for GI cancers 3.Tumor specific antigen for a variety of cancers 4.Embryonic and germ cells effects

20. 20 Risk Assessment Process In 1983 the National Academy of Sciences divided the risk assessment process into 4 distinct elements: 1. Hazard identification 2. Dose-response assessment 3. Human exposure assessment 4. Risk characterization

21. 21 Risk Management Issues  Risk Characterization: quantitative ( 定量 ) vs. qualitative ( 定性 ) ;  Legal Factors: uncertainty and challenges, enforcement;  Economic and Social Factors: impact to industries and society;  Public Concern: fear of harm, uncertainty of protection, variation in response to harm.

22. Conclusions Understand toxicity of products and medical activities for the prevention of health effects Understand susceptibility for improvement of outcomes Monitor activities (post-market) for validation of efficacy or toxicity Identify toxic substances and prevent human exposure to them Risk characterization and management.