Environ. Eng. NOTE 11

1. Environ. Eng. NOTE 11 • Risk Assessment (Masters and Ela, Ch. 4) - Introduction and Concepts - Risk Assessment - Hazard Identification - Dose-Response Assessment - Human Exposure Assessment CEE3330-01 Joonhong Park Copy Right

2. Introduction • In the 1980’s, the acceptance of the role of risk assessment and risk management in environmental decision making. (USA) • Publics and societies recognized the threats from hazardous waste/pollutants (Rachael Carson, “Silent Spring”; Orange Agents for Vietnam War etc.) • Risk Assessment: the gathering of data that are used to relate response to dose (scientific side). • Risk Management: decision making, under extreme uncertainty, about how to allocate national resources to protect public health and the environment (policy side) CEE3330-01 Joonhong Park Copy Right

3. Perspectives on Risks • Risk is a probability of someone dying due to a death-causing disease in a place and time. • For example: In 2006, 564,800 were predicted to be caused by cancer among 2,393 million predicted death in USA. (=> 24 % of cancer risk in the USA of the year) • Time-duration dependent: lifetime risk, annual risk • Individual health and activity dependent: healthy young man vs. old man; smoker vs. non-smoker • When risks are based on models, there are generally very large uncertainties in the estimates.

8. Perception on Risk • There are a number of attributes of risk that can increase the anxiety level of someone evaluating his or her won person exposures. • For Example) More comfortable living next to a gas station, despite the exposure to the carcinogen benzene, than living anywhere near a nuclear power plant, with its perceived unknown and uncertain risks.

10. Risk Assessment Causally linked to particular Health effects? How much of dose cause adverse health effect? Who will be exposed to the toxicants? (size and nature of populations) Integration of the above three steps to determine the magnitude of the public-health problem

11. Hazard Identification • Goal:To determine whether or not the chemical that a population has been exposed to are likely to have any adverse health effects (Toxicological Issues and Questions) • Pathways of Toxicant into Human Body: • Ingestion with food or drink • Inhalation (breathing) • Contact with the dermal or other exterior surfaces, such as the eyes • Organ-Specific Toxicity (see =>) • Side Effects by Toxic Chemicals • Heavy metal causing kindneys/liver failure • Carbon monoxide and nitrate toxicity in oxygen delivery in blood • Lung malfunction by cigarette smoke, ozone, asbestos, small particles etcs. • Skin reacts with a variety of chemicals The circulatory system and nomenclature of toxic effects: hepatotoxicity (liver), nephrotoxicity (kidneys), pulmonotoxicity (lungs),hematotoxicity (blood). [Source: Based on James, 1985]

12. Fate of toxicants in the body Fate of chemical toxicants in the body (Source: Environ. 1988)

13. Hazard Identification • Acute Toxicity • Mutagenesis • Carcinogenesis • Toxicity Testing in Animals • Human Studies • Weight-of-Evidence Categories for Potential Carcinogens

14. Acute (급성) Toxicity • Philippus Aureolus Theophrastus Bombastus von Hohenheim-Paracelsus, “It is the dose that makes the poison”. • One measure of the toxicity of something is the amount needed to cause some acute response, such as organ injury, coma, or even death. (opposite concept: chronic response). [Normalizing the dose using body weight] • Not every member of an exposed population will react the same way to a toxin.

15. Mutagenesis DNA (deoxyribonucleic acid) Teratogens Carcinogens Possible consequences of a mutagenic event in somatic and germinal cells

16. Carcinogenesis • Cancer • In 2006, nearly 1.4 million new cancer cases were diagnosed in the US, and over one-half million people die each year from cancer. Cancer is truly one of the most dreaded diseases. • In the initiation stage, a mutation alters a cell’s genetic material in a way that may or may not result in the uncontrolled growth of cells that characterizes cancer. • In the promotion, stage of development, affected cells no longer recognize growth constraints that normally apply, and a tumor develops. • Metastasis: Tumor breaks apart and portions of it enter other areas of other body. • One-hit hypothesis: exposure to even the smallest amount of a carcinogen leads to some nonzero probability that a malignancy will result. (a conservative and worst-case risk assessment for carcinogens)

17. Toxicity Testing in Animal 1. Acute toxicity 2. Chemical similarity analysis 3. Toxicity testing with bacteria (Ames mutagenicity assays) 4. Intermediate testing with animal organs 5. Final testing with animals (chronic carcinogenesis bioassay) - Two species of rodents must be tested. - At least 50 males and 50 females - At least two dose to be administrated (max. tolerant dose [MTD] included) - 2-3 years operation (cost for chemical? animals?)

18. Human Studies Human response may or may not be different from animal’s response to a toxicant. It is difficult to extrapolate any conclusion for human from testing with animals. Data sources for human studies: victims of tragedies (e.g., toxicant spill) and epidemiologic studies (always careful caution must be exercised in anlaysis) - Relative risk = [a/(a+b)] / [c/(c+d)] - Attributable risk = [a/(a+b)] - [c/(c+d)] - Odds ratio = ad/bc when its value is 1.0

19. Weight-of-Evidence Categories forPotential Carcinogens (US EPA) Group A (Human Carcinogen): A substance is put into this category only when sufficient epidemiologic evidence supports a causal association beteen exposure to the agent and cancer. Group B (Probable Human Carcinogen): This group is actually made up of two subgroups. An agent is categorized as B1 if there is limited epidemiologic evidence; and an agent is put into B2 if there is inadequate human data but sufficient evidence of carcinogenicity in animals. Group C (Possible Human Carcinogen): This group is used for agents with limited evidence of carcinogenicity in animals and an absence of human data. Group D (Not Classified): This group is for agents with inadequate human and animal evidence or for which no data are available. Group E (Evidence of Noncarcinogenicity): This is used for agents that show no evidence for carcinogenicity in at least two adequate animal tests in different species or in both adequate epidemiologic and animal studies.

20. Dose-Response Assessment Hypothetical dose-response curves

21. Extrapolations from High Doses to Low Doses The most controversial: Extrapolating from the high doses actually administrated to test animals to the low doses to which humans are likely to be exposed. The choice of extrapolation models is strictly a policy decision. One common models: 1) one-hit model: P(d) = 1 – exp(-q0 – q1d) P(d): risk (probability) as a function of dose (d) d: dose q0, q1: fitting parameters 2) Multistage model: P(d) =1-exp(-q0-q1d-q2d^2-qnd^n) 3) Linearized multistage model (US EPA) Hypothetical dose-response curves

22. Potency Factor for Carcinogens The potency factor (PF) is the slope of the dose-response curve. It can also be thought of as the risk that corresponds to a chronic daily intake of 1 mg/kg-day. Incremental lifetime cancer risk PF= Chronic daily intake [CDI](mg/kg-day) PF values can be found in an EPA database on toxic substances called the Integrated Risk Information System (IRIS). CDI(mg/kg-day) = Ave. daily dose (mg/day)/Body weight (kg)

23. The Reference Dose for Noncarcinogenic Effects LOEL: the lowest-observed-effect level NOEL: no-observed-effect level NOAELs: no-observed-adverse-effect levels RfD: reference dose (acceptable daily intake [ADI])

24. The Hazard Index for Noncarcinogenic Effects Average daily dose during exposure period (mg/kg-day) Hazard quotient = RfD (for individual chemical) Hazard index = Sum of Hazard quotients for all the toxicants in environment

25. Human Exposure Assessment Bioconcentration and Contaminant degradation

26. Risk Characterization • The National Academy of Science (1983) suggests a number of questions that should be addressed in a final characterization of risk, including the following: • What are the statistical uncertainties in estimating the extent of health effects? • What are the biological uncertainties? What are their origins? How will they be estimated? What effect do they have on quantitative estimates? How will the uncertainties be described to agency decision makers? • Which dose-response assessments and exposure assessments should be used? • Which population groups should be the primary targets for protection, and which provide the most meaningful expression of the health risk?