PHAR 303 Lecture 10: Lecture 10 Risk Assessment
11 May 2018
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Lecture 10 (Feb 8th) Risk Assessment & Management
• The systematic scientific characterization of potential adverse health effects from human and environmental
exposures (human toxicity & ecotoxicity)
• Risk is trying to evaluate the probability of an adverse outcome under specified conditions. What adverse
condition at your looking at? How do you weight those together to calculate the probability of an effect?
• Ex. Hazard : UV sunlight Exposure: staying under w/o protection (exposure required for risk)
• If cyanide is locked away and labeled, it is hazardous but very low risk of exposure..if it’s accessible, in the
kitchen or in tea will increase the risk.Goal:
1. Protect human & ecological health from toxic substances
2. Balance risks & benefits of substances like drugs, pesticides (could be + - ) adverse effects?
3. Set target levels of risks in food contaminants, water pollutants. What’s the amount people will accept in terms of
adverse effects?
4. Set priorities for program activities – regulatory agencies, manufacturers, environmental/consumer organizations.
Regulatory agencies spend a lot of time assessing hazard & exposure & determine risk & present it to legislators.
Manufactures would like to have safe products because lose money if have to start the production again. They don’t
necessarily have the resources or requirements to prove that their safe before they put in the product. If you buy a
product at Canadian Tire or Waltmart, they do not know everything that is in the substances. They get it from
distributor, go gets it elsewhere. Chain of information & the manufacturer don’t necessarily give the info down the
chain. Once the chemical company sold the product to manufacture, they are not required to give these data too.
5. Estimate residual risks & extent of risk reduction after steps are taken to reduce risks.
Risk = Hazard x Exposure
1. Hazard identification – what are potential health effects?
• Dose Response Assessment – what are health effects at different exposure levels?
• Exposure assessment – what’s the exposure levels in the population?
2. Risk Characterization – what is the risk of a health effect occurring in the population? (EPA)
1. Hazard identification
Characterization of the Innate Adverse Toxic Effects of Agents: Weight-of-evidence approach. Look into the
literature.
If you ask “does chemical X cause cancer?” You can have
➢ 1 good animal study but no human studies (possibly causes cancer)
➢ Some evidence in human epidemiologic studies or >2 good animal studies (probably cause cancer)
➢ Good evidence in human studies (known cause cancer)
• Structure-Activity Relationships – what kind of chemical it is?
o Structure, solubility, stability, pH, sensitivity, electrophilicity, reactivity
o Endpoints
o 3D molecular modeling
Read Across Approach – Using data from a similar chemical(s) to predict endpoint or property information for one or
more substances that lack empirical data. Can be qualitative or quantitative. You can miss info in different chemicals.
In chemical 1, you may know its pH but in chemical 2 you may know its structure. Based on read across, maybe they
fall in the same category (extrapolate). Based on what you know, predict for other chemicals. Most of regulatory
agencies do not have the resources to do all the testes, neither authority to make the chemical companies to provide
data. For drugs, pharmaceuticals must provide the data. For chemicals (used to produce a product & not for human use
but they’re in the env.) they don’t need to provide data.
• In vitro and short term tests
o Bacterial/cell mutagenicity assays
o Cell free corrosivity test
o Pathway based cell assays (TOX21) can have reporter genes for specific pathways that might be activated by
estrogenicity (maybe)
• Animal bioassays
o Acute/chronic toxicity tests (6)
o Carcinogenicity : 2 species, both sexes, near lifetime (long) exposure
o Reproductive & developmental toxicity (more expensive)
• Epidemiologic data – these will add to your evidence that there will have a human exposure associated with an
adverse health effect.
• Strength of association
• Consistency of observations
• Specificity, Dose response, Biological plausibility, Biomarkers.
• Temporal relationship – ex. maybe it causes adverse effects 8 months later.
find more resources at oneclass.com
find more resources at oneclass.com
Document Summary
How do you weight those together to calculate the probability of an effect: ex. Hazard : uv sunlight exposure: staying under w/o protection (exposure required for risk) What"s the amount people will accept in terms of adverse effects: set priorities for program activities regulatory agencies, manufacturers, environmental/consumer organizations. Regulatory agencies spend a lot of time assessing hazard & exposure & determine risk & present it to legislators. Manufactures would like to have safe products because lose money if have to start the production again. They don"t necessarily have the resources or requirements to prove that their safe before they put in the product. If you buy a product at canadian tire or waltmart, they do not know everything that is in the substances. They get it from distributor, go gets it elsewhere. Chain of information & the manufacturer don"t necessarily give the info down the chain.
