Dose-response relationship exposure assessment

Risk assessment An empirically based paradigm that estimates the risk of adverse effects) from exposure of an individual or population to a chemical, physical or biological agent. It includes the components of hazard identification, assessment of dose-response relationships, exposure assessment and risk characterization. 

See also Carcinogen Classification Schemes Dose-Response Relationship Exposure Assessment Exposure Criteria Hazard Identification Risk Assessment, Ecological Risk Based Corrective Action (RBCA) Risk Characterization Risk Communication Risk Management Uncertainty Analysis. 

See also Dose-Response Relationship Exposure Assessment Risk Assessment, Human Health Risk Management. 

See also Behavioral Toxicology Dose-Response Relationship Exposure Assessment Mixtures, Toxicology and Risk Assessment Multiple Chemical Sensitivities Neurotoxicity Pollution, Air Indoor Psychological Indices of Toxicity Respiratory Tract Sensory Organs. 

Hazard characterization and delineation of dose-effect or dose-response relationships. 3. Assessment of exposure 4. Risk characterization... 

Immunotoxicity. There are currently no data on the effects of 2-hexanone on the human immune system via any route of exposure. Animal data included an inhalation study in which there was a 40% decrease in peripheral white blood cells in rats exposed to 2-hexanone (Katz et al. 1980). In addition, 2,5-hexanedione, a metabolite of 2-hexanone, was shown to adversely affect lymphoid organs of the immune system in rats and to cause impairment of immunity in mice (Upreti and Shanker 1987). Immunological assessments, including analysis of peripheral blood components and effects on lymphoid tissue, conducted as part of intermediate-or chronic-duration studies and skin sensitization tests would be useful in developing a dose-response relationship and assessing the potential risk to chronically exposed persons in the vicinity of hazardous waste sites or to exposed workers. 

See also Aggregate Exposures Dose-Response Relationship Risk Assessment, Ecoiogicai Risk Assessment, Human Heaith. 

See also American Conference of Governmental Industrial Hygienists Biomarkers, Human Health Biotransformation Dose-Response Relationship Exposure Hazard Identification Medical Surveillance Occupational Safety and Health Administration Psychological Indices of Toxicity Risk Assessment, Ecological Risk Assessment, Human Health. 

If possible, there should be measurement of the toxic effect in order quantitatively to relate the observations made to the degree of exposure (exposure dose). Ideally, there is a need to determine quantitatively the toxic response to several differing exposure doses, in order to determine the relationship, if any, between exposure dose and the nature and magnitude of any effect. Such dose—response relationship studies are of considerable value in determining whether an effect is causally related to the exposure material, in assessing the possible practical (in-use) relevance of the exposure conditions, and to allow the most reasonable estimates of hazard. 

Dose—response relationships are useful for many purposes in particular, the following if a positive dose—response relationship exists, then this is good evidence that exposure to the material under test is causally related to the response the quantitative information obtained gives an indication of the spread of sensitivity of the population at risk, and hence influences ha2ard evaluation the data may allow assessments of no effects and minimum effects doses, and hence may be valuable in assessing ha2ard and by appropriate considerations of the dose—response data, it is possible to make quantitative comparisons and contrasts between materials or between species. 

Dose-response assessment is the process of obtaining quantitative information about the probability of human illness following exposure to a hazard it is the translation of exposure into harm. Dose-response curves have been determined for some hazards. The curves show the relationship of dose exposure and the probabihty of a response. Since vahdated dose-response relationships are scarce, various other inputs are used to underpin the hazard characterization phase of risk assessment. 

Decision Analysis. An alternative to making assumptions that select single estimates and suppress uncertainties is to use decision analysis methods, which make the uncertainties explicit in risk assessment and risk evaluation. Judgmental probabilities can be used to characterize uncertainties in the dose response relationship, the extent of human exposure, and the economic costs associated with control policies. Decision analysis provides a conceptual framework to separate the questions of information, what will happen as a consequence of control policy choice, from value judgments on how much conservatism is appropriate in decisions involving human health. 

Dose-response relationships for two animal carcinogens, strikingly different in potency, are presented in Tables 6.2 and 6.3. The type of information presented in the tables is the usual starting point for risk assessments as we shall see, human exposures to these carcinogens are very much less than the NOAELs and LOAELs from the animal data. 

The delayed neurotoxicity smdies of organophosphorus substances provide information on the delayed neurotoxicity arising from repeated exposure over a relatively limited period of the animal s life span. The smdy is used in the assessment and evaluation of the neurotoxic effects of organophosphorus substances and will provide information on dose-response relationship and can provide an estimate of a NOAEL for delayed neurotoxicity. See also Section 4.7.7. 

FIGURE S.6 Schematic illustration of the traditional setting of an acceptable level of exposure (ADI) by dividing the NOAEL from an animal study by an assessment factor (AF). The two dose-response relationships have identical NOAEL. If a uniform assessment factor is applied, there will be an adequate MOS at the ADI for effect b but not for effect a. (Modified from KEMI, Human health risk assessment. Proposals for the use of assessment (uncertainty) factors. Application to risk assessment for plant protection products, industrial chemicals and biocidal products within the European Union. Report No. 1/03, Solna, Sweden, 2003. 

An additional assessment factor, of up to 10, has been apphed in some cases where the NOAEL has been derived for a critical effect, which is considered as a severe and irreversible effect, such as teratogenicity or non-genotoxic carcinogenicity, especially if associated with a shallow dose-response relationship. The principal rationale for an additional factor for nature of toxicity has been to provide a greater margin between the exposure of any particularly susceptible humans and the dose-response curve for such toxicity in experimental animals. 

Dose-response assessment today is generally performed in two steps (1) assessment of observed data to derive a dose descriptor as a point of departure and (2) extrapolation to lower dose levels for the mmor type under consideration. The extrapolation is based on extension of a biologically based model (see Section 6.2.1) if supported by substantial data. Otherwise, default approaches that are consistent with current understanding of mode of action of the agent can be applied, including approaches that assume linearity or nonlinearity of the dose-response relationship, or both. The default approach is to extend a straight line to the human exposure doses. 

An exposure assessment is the quantitative or qualitative evaluation of the amount of a substance that humans come into contact with and includes consideration of the intensity, frequency and duration of contact, the route of exposure (e.g., dermal, oral, or respiratory), rates (chemical intake or uptake rates), the resulting amount that actually crosses the boundary (a dose), and the amount absorbed (internal dose). Depending on the purpose of an exposure assessment, the numerical output may be an estimate of the intensity, rate, duration, and frequency of contact exposure or dose (the resulting amount that actually crosses the boundary). For risk assessments of chemical substances based on dose-response relationships, the output usually includes an estimate of dose (WHO/IPCS 1999). 

If the hazard assessment indicates that the compound is potentially hazardous, the next step is to evaluate the various possibilities for exposure. What is the most likely route of exposure oral, inhalation or skin How much absorption is expected from the different routes of exposure Information is also needed on amount, duration, and frequency of exposure. Is exposure occurring in the home, workplace, school, or other areas This information helps to define the population of concern. Exposure information may also be important for designing appropriate studies on hazard assessment and certainly for the next step of establishing dose-response relationships. 

Next, it is important to characterize the dose-response relationship for the agent. Data from the initial hazard assessment, combined with exposure assessment information, are used to determine the most sensitive endpoint. Available data are used to define the dose at which there is no observed effect (NOAEL - no observed adverse effect level) and the shape of the dose-response curve (Figure 19.1). It may be necessary to perform additional studies to define the dose-response curve. 

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