Risk characterization Flashcards
what falls under risk characterization?
-Limitations and assumptions in risk assessment
-Cancer vs non-cancer risk assessment
-Characterization of cancer risks
-Characterization of non-cancer risks
-Characterization of risk using mathematical modelling.
Limitations and assumptions in risk assessment
Risk
Risk assessment is a process that provides a framework for evaluating information and presenting that information.
Risk assessment is limited by:
1.Lack of data on substances and adverse health effects
2.Uncertainty about the cause of disease
3.Uncertainity in extrapolating human risk from animal data.
Limitation
1.In the absence of adequate human data, adverse effects in experimental animals are regarded as indicative of adverse effects in humans.
2.Dose-response models can be extrapolated outside the range of experimental observations to yield estimates.
3.Observed experimental results can be extrapolated from one species to the other.
4.No threshold doses exist for carcinogenesis.
5.Average doses give a reasonable measure of exposure when dose rates are not constant.
6.In the absence of toxicokinetic data, the effective or target dose is assumed to be proportional to the administered dose.
7.The risk from multiple exposure and multiple sources to the same chemical are usually assumed to be additive.
8.Regardless of the route of exposure,100% absorption across species is assumed in the absence of specific evidence to the contrary.
9.Results associated with a specific route of exposure are potentially relevant for other routes of exposure.
Characterization of cancer risks (non-carcinogen)
-For food additives, NOAEL is divided by a safety or uncertainty factor to estimate an acceptable daily intake.
NOAEL/safety or uncertainty factor=ADI
-For systemic toxicants, Us EPA developed the reference dose approach, where the NOAEL is divided by an uncertainty factor and modifying factor.
NOAEL/uncertainty factor and modifying factor.
-Generally, the RfD is an estimate of daily exposure to the human population that is likely to be without an appreciable risk of harmful effects during a lifetime.
Characterization of cancer risks (Genotoxic carcinogens)
- Risk estimated from the cumulative dose
-Mathematical models are used to
extrapolate to low dose response.
-A range of risks might be produced using different models and assumptions about dose-response curves, relative sensitivities of humans and animals
Characterization of risks using mathematical modelling
1.Postive response in rodent bioassay
2.Appropriate dose measure
3.Dose response function selected for risk to rodents.
4.Estimates of the variability of the dose response functions.
5.Determine quantitative value for risk assessment for rodents.
6.Interspecies extrapolation to estimate risk for humans in dose region of interest.
7.Extrapolation from one exposure route to another
8.Exposure analysis and risk benefit
analysis to determine exposure levels and risks society can tolerate.
