Evaluation of Toxicity.pptx

Assessment of acute and chronic toxicity are explained well in this presentation. Major steps in human health risk assessment are discussed in detail.

1. Evaluation of Toxicity V.Vijitha Lectrurer (Prob.) Dept. of Biosystems Technology FoT , UoJ

2. Toxicity Assessment Basics Toxicity assessment is a major component of risk assessment I t provides an estimate of how much of a substance causes what kind of harm.

3. Toxic Effects Toxic effects are classified as either acute or chronic Acute effects happen very rapidly after a single exposure has occurred Food poisoning Breathing fumes from a chlorine spill Death

4. Chronic effects happen only after repeated long-term exposure C igarette smoking E ating foods with low levels of contaminants B reathing polluted air E xamples of chronic effects Cancer O rgan damage Reproductive difficulties Nervous system impairment

5. Chronic effects fall into two categories Carcinogenic effects - Cancer Non-carcinogenic effects Organ damage: Damage in liver from long-term alcohol consumption Reproductive difficulty: Decreased fertility from the pesticide dibromochloropropane Nervous system impairment: Mental retardation in people exposed to high levels of lead during early childhood

6. All quantitative toxicity assessments are based on the dose-response concept. Increase the dose (exposure), the response (toxicity) also increases. Acute toxic effects are estimated by: LD50 studies or Observation of accidental exposures Chronic toxic effects are estimated by dose-response studies on animals. Especially, the carcinogenic effects are estimated by study called carcinogenesis bioassay.

7. Assessing Acute Toxicity Acute toxicity of chemicals to humans comes from accidental poisonings or exposures. Eg : Drug overdoses, Chemical spills Scientists also use animal tests called LD50 (Lethal Dose) studies to assess acute toxicity. These studies determine the amount of a substance that will kill half the test animals in 14 days. LD50 is stated in mg of chemical per kg of body weight.

8. Ex: A reported "rat oral LD50 of 50 mg/kg" means that half of the rats that ingested a dose of 50 mg of the substance per kg of body weight died within 14 days LD50 values are unknown for humans , since LD50 experiments are not conducted on humans. If the LD50 is 50 mg/kg: The lethal amount for a child would be 50 mg/kg times 10 kg , which equals 500 mg (about 1/8 tsp.) The lethal amount for an adult would be 50 mg/kg times 70 kg , which is 3,500 mg (about 3/4 tsp.)

9. Assessing Chronic Toxicity Carcinogenic Assessment Test animals are administered different large doses of a substance daily over a lifetime (24-30 months in rats) At the end of the study, the animals are examined to see if cancer can be found . If cancer is found, scientists use: available data and mathematical models to estimate the cancer incidence at the lower doses more likely to occur in the environment.

10. Example of a carcinogenesis bioassay A carcinogenesis bioassay was performed for benzene on both rats and mice. Both sexes of each species got leukemia at the high doses administered. Result of extrapolating the cancer incidence at high dose to low dose and from rodents to humans in the risk estimation is given below: Benzene dose of 1 mg/kg/day will result in 3 cancers per 100 people exposed daily for a lifetime to that dose

11. Non-Carcinogenic Assessment Non-carcinogenic chronic toxicity is assessed by administering varying amounts of a substance (dose) to laboratory animals and noting the effects (responses ). Essentially, the scientists look for the smallest dose that causes any detectable effect. This smallest dose is called the Lowest Observable Effect Level (LOEL ). Scientists also determine the highest dose at which no effects occur which is termed as NOEL. The NOEL is considered the "safe level" for that chemical in the species

12. Role of Toxicity Assessment Toxicity assessment provides information on how much of a chemical causes what kind of harm. As the toxicity assessment is based on an animal study , the degree of harm to humans must be extrapolated using mathematical models . It is done based on a variety of assumptions. Thus the toxicity assessment provides only an estimate of the harm to humans.

13. Human Health Risk Assessment

14. HHRA is a screening tool that helps individuals to, Identify and understand their health risks Monitor health status over time It includes a questionnaire, an assessment of health status, and personalized feedback about actions that can be taken to: Reduce risks Maintain health Prevent disease

15. A health risk assessment usually includes questions in the following areas: Demographic characteristics : age, gender Lifestyle behaviours : exercise, eating habits, alcohol and tobacco use Emotional health : mood, stress, life events Physical health : weight, blood pressure, cholesterol levels Current and previous health conditions

16. Planning and Scoping Human health risk assessment starts with a good plan regarding the, Purpose, scope, and technical approaches that will be used Risk assessors will typically ask the following questions 1. Who/What/Where is at risk? Individual General population Life stages

17. 2. What is the environmental hazard of concern? Chemicals (single or multiple/cumulative risk) Radiation Physical (dust, heat) Microbiological or biological Nutritional (for example, diet, fitness, or metabolic state)

18. 3. Where do these environmental hazards come from? Point sources (smoke or water discharge from a factory) Non-point sources (automobile exhaust, agricultural runoff) Natural sources 4. How does exposure occur? Air Surface Water Groundwater Soil Solid Waste Food Non-food consumer products, pharmaceuticals

19. 5. What does the body do with the environmental hazard and how is this impacted by factors such as age, race, sex, genetics, etc.? Absorption - does the body take up the environmental hazard Distribution - does the environmental hazard travel throughout the body or does it stay in one place? Metabolism - does the body break down the environmental hazard? Excretion - how does the body get rid of it?

20. 6. What are the health effects? Some health effects include cancer, heart disease, liver disease and nerve disease 7. How long does it take for an environmental hazard to cause a toxic effect? Does it matter when in a lifetime exposure occurs? How long? Acute - right away or within a few hours to a day Subchronic - weeks or months Chronic - a significant part of a lifetime or a lifetime Timing Is there a critical time during a lifetime when a chemical is most toxic ( fetal development, childhood and during aging)?

21. Steps-HHRA Step 1: Hazard Identification Step 2: Dose Response Step 3: Exposure Assessment Step 4: Risk Characterization

22. Step 1: Hazard Identification Objective: Identify the types of adverse health effects that can be caused by exposure to some agent Eg : Cancer and Birth defects Key Components of Hazard Identification Toxicokinetic : Considers how the body absorbs , distributes , metabolizes , and eliminates specific chemicals. Toxicodynamic : Focus on the effects that chemicals have on the human body

23. Step 2: Dose Response Objective: Document the relationship between dose and toxic effect A dose-response relationship describes how the likelihood and severity of adverse health effects are related to the amount and condition of exposure to an agent Typically, as the dose , the measured response At low doses there may be no response .

24. Dose-response relationships observed from animal studies. Animal studies must also be extrapolated from that animal species to humans. It is done only to predict the relationship for humans. It helps to find the NOAEL. Therefore the critical region where the dose level begins to cause the adverse effect in the human population can be identified.

25. Step 3: Exposure Assessment Objective: Calculate a numerical estimate of exposure or dose. Exposure assessment is the process of measuring or estimating the, Magnitude Frequency Duration of human exposure to an agent in the environment .

26. An exposure assessment includes some discussion of the, Size Nature Types of human populations exposed to the agent. Exposure can be measured directly . But more commonly is estimated indirectly through: Consideration of measured concentrations in the environment Consideration of models of chemical transport and fate in the environment Estimates of human intake over time

27. Exposure assessment considers 3 facts Exposure pathway (the course an agent takes from its source to the person(s) being contacted) Exposure route (means of entry of the agent into the body) It is described as intake (taken in through a body opening) or uptake (absorption through tissues ). Range of Exposure There is a range of exposures actually experienced by individuals for any specific agent or site Some individuals may have a high degree of contact for an extended period

28. Step 4: Risk Characterization Objective : Summarize and integrate information from the proceeding steps of the risk assessment to synthesize an overall conclusion about risk Principles of conducting risk characterizations Transparency The characterization should fully and explicitly disclose the risk assessment

29. Clarity The products from the risk assessment should be readily understood by readers inside and outside of the risk assessment process Consistency The risk assessment should be conducted and presented in a manner which is consistent with EPA policy

30. Reasonableness The risk assessment should be based on sound judgment , with methods and assumptions consistent with the current state-of-the-science It should be conveyed in a manner that complete , balanced and informative

31. Thank You