Term
| Fundamental issues and considerations |
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Definition
*risk characterization is the integration of toxicity and exposure assessment
**can only be as good as its parts
*should fully, openly, and clearly characterize risks and disclose analysis, uncertainties, and assumptions
**document sources for processes and protocols |
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Term
| Non-standard pollution groups |
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Definition
| *care must be taken to ensure that assumptions about population parameters in the dose-response analysis are consistent with the population parameters used in the exposure analysis |
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Term
| Adjustment for chemical absorption |
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Definition
*may be necessary to ensure that the exposure estimate and the toxicity value being compared during the risk characterization are both expressed as absorbed or administered doses
**adjustments are made for vehicles of exposure, administered to absorbed dose for RfD and SFs |
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Term
| Aggregate effects of chemical mixtures |
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Definition
*when combining multi-chemical risk estimates for multiple chemical sources, it should be noted that
**if two sources do not affect the same individual or subpopulation, the sources' individual risk should not be combined
**in mixture assessment (within the context for interactions):
***carcinogenic effects--segregated by weight-of-evidence category
***non-cancer effects--grouped by similar toxic endpoint/mode of action |
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Term
| Fundamental considerations in health assessment of carcinogens |
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Definition
*qualitative issues:
**weight-of-evidence--from case studies, epidemiological studies, long-term animal studies, long-term bioassays, short-term tests, and SARs
**mechanistic inference--multistage process that is characterized by a non-threshold assumption
***may not be true for each step, only for the process as a whole
**exposure route specificity--some chemicals may not pose a carcinogenic effect via ingestion, but may pose a carcinogenic risk via inhalation
**role of epidemiological data--can give more weight to a well-designed epi study rather than a well-designed animal study, remembering that the potential for association remains especially relevant for animal data
**sensitive and susceptible populations--independently address the associated health concerns
**structure activity relationships (SARs)--can be crucial in estimating toxicity factors for those chemicals that have little or no data available
**chemical interactions--we assume an additive effect, but we have to make a qualitative statement about the certainty of this with regard to mode of action
*quantitative issues
**dose scaling--from animal to human and when using epi studies
***individual sensitivities
**pharmakokinetics/pharmacodynamics--delivered dose rather than the exposure dose is important
***using exposure dose is conservative in most cases
**mechanistic considerations--extrapolations from high to low doses must consider which mathematical model to use
***most conservative model is best if there are equally plausible models
**individual vs. population risk--if possible experimental models, molecular biology, and epidemiology should be used to make the best estimate of risk |
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Term
| Carcinogenic risk effects |
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Definition
*calculated using one of two models, then take the sum for all carcinogens in the assessment
**linear low dose: CR = CDI * SF
***based on linearized multistage model assuming multiple stages for cancer
***good for low intake levels
**one-hit model: CR = 1 - exp(-CDI*SF)
***assumes single stage for cancer and that one molecular or radiation interaction induces malignant change
***good for high intake levels
**if risk is greater than 1 in 1 million, this is considered unacceptable |
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Term
| Non-carcinogenic risk effects |
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Definition
*hazard quotient
**HQ = E/RfD
**for each chemical
*hazard index
**HI = ΣHQi
**summation of the HQ for each chemical in the assessment
*if the hazard index is greater than 1, this indicates unacceptable risk |
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Term
| Population excess cancer burden |
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Definition
*to assess the population cancer burden associated with a chemical exposure problem:
**one can estimate the number of cancer cases due to an exposure source within a given community (cancer burden)
Bgi = Σ (Rgi * Pg)
***Bgi = excess cancer burden for a group
***Rgi = excess lifetime cancer risk for a group
***Pg = number of persons in exposed population group |
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Term
| Uncertainty and variablity |
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Definition
*variability--arises from true heterogeneity in characteristics such as
**dose-response differences
**differences within a population
**differences in exposure factors
**differences in exposure levels
*uncertainty--arises from lack of knowledge about factors |
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Term
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Definition
*spatial--across locations
**can be regional or local (i.e. fish intake)
*temporal--across time
*inter-receptor--amongst individual receptors
**human characteristics and behaviors |
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Term
| Types and nature of uncertainty |
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Definition
*parameter values
**incomplete or biased data
*parameter modeling
**model inadequacy or representation of situation
*degree of completeness
**representativeness of evaluation scenarios |
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Term
| Sources of uncertainty in human health assessment |
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Definition
*health effects
**toxicity data
*measuring or calculating exposure point concentrations
*calculating exposure dose |
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Term
| Commonly encountered limitations |
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Definition
*toxicity extrapolations
*adjustments in dose-response evaluation
*toxicity of mixtures
*models
*background exposures
*representativeness of sampling plan |
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Term
| Uncertainty and variability analysis |
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Definition
*uncertainty/sensitivity analysis
**involves identifying parameters that will make the most contribution to uncertainty
**estimating the most appropriate value using distributions and non-point estimates
**provides full spectrum of information |
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Term
| Qualitative analysis of uncertainties |
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Definition
*determination of the general quality and reasonableness of the risk management data, parameters, and results
*most important for screening and preliminary assessments
*can contain errors, incomplete analysis, limitations, bad assumptions |
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Term
| Quantitative analysis of uncertainties |
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Definition
*Monte Carlo simulations
**assign a probability distribution to input variables
**estimate risk using an iterative process to calculate risk by changing the input variables in the risk equation
**produces a risk distribution instead of a point estimate |
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Term
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Definition
*measures relative response of output variables caused by variations of the input variables and parameters
*purpose is to identify the influential input variables and to develop bonds on the model output
*more resources can be directed to reduce the uncertainty in the most sensitive parameter |
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