Quantitative risk assessment exposure assessments

Exposure assessment is one of the four major steps in the risk assessment paradigm, as defined by the National Academy of Sciences in the United States. Thus, exposure assessment is a key element in any quantitative risk assessment. Exposure assessment is... 

The purpose of this chapter is not to discuss the merits, or lack thereof, of using plasma cholinesterase inhibition as an adverse effect in quantitative risk assessments for chlorpyrifos or other organophosphate pesticides. A number of regulatory agencies consider the inhibition of plasma cholinesterase to be an indicator of exposure, not of toxicity. The U.S. Environmental Protection Agency, at this point, continues to use this effect as the basis for calculating the reference doses for chlorpyrifos, and it is thus used here for assessing risks. 

While profound immunosuppression can lead to an increased incidence of infectious or neoplastic diseases, interpreting data from experimental immunotoxicology studies or epidemiological studies for quantitative risk assessment purposes can be problematic. This is because inadvertent exposures to immunotoxic agents may often be expressed as a mild-to-moderate change, reflected, for example, by a 15 to 25% decrement in an immune parameter compared to control values. To help address the clinical consequences of mild-to-moderate immunosuppression, we examined available experimental, clinical and epidemiological studies that examined the association between suppression of immune function and infectious disease, independent of the etiology of suppression. 

In this paper I have tried to show that measurement of health benefits attributable to TSCA is not feasible. I hope that in doing so I have not belabored the obvious. For new chemicals and for most existing chemicals, prospective evaluation of health benefits to be achieved by various exposure controls will have to be based on extrapolation from microbial and animal data. However, while such extrapolation may be useful in a qualitative sense, quantitative risk assessment techniques involve considerable uncertainty, and in any case have not been developed for chronic effects other than cancer. 

Battelle and. Crump KS, and Co., Inc. 1986. Quantitative risk assessment for 1,4-dichlorobenzene prepared for Exposure Evaluation Division. U.S. Environmental Protection Agency, Office of Toxic Substances, under Contract No. 68-02-4246. 

Valid epidemiological studies are preferable for the quantitative risk assessment of genotoxic carcinogens for the purpose of deriving a tolerable intake. If such data are available, for example in the working environment, they can be used quantitatively to convert work exposure to lifetime exposure, i.e., to convert intermittent exposure to continuous exposure (see Section 5.1 for adjustment of concentrations). However, as addressed in Chapter 3, valid human data are seldom available. 

The most widely used of the many mathematical models proposed for extrapolation of carcinogenicity data from animal studies to low-dose human exposures (i.e., low-dose extrapolation) is the LMS model. This has, in effect, become the default approach for quantitative risk assessment and has been used by, e.g., the US-EPA for many years as well as by the WHO in relation to derivation of drinking-water guideline values for potential carcinogens (WHO 1996) (see Section 9.2.1.2 for drinking-water guideline values). 

The chemical industry has historically been the top TRl emitter, but by figuring in toxicity and exposure, the baton has been passed to a new leader—the primary metals industrial sector. The model does not provide chemical-specific quantitative risk assessments. Instead, EPA developed toxicity weights for each chemical. Those are combined with exposure, fate, and transport information to generate an indicator value for the health impact of emissions from a particular factory (Johnson, 1999). 

Roller, M. (2006) Quantitative risk assessment for the exposure to toner emissions from copiers. Gefahrstoffe-Reinhaltung der Lufi, 66, 211-6. 

A different approach, called a quantitative risk assessment, is used for nonthreshold effects, such as cancer. Sophisticated statistical models are used to extrapolate the experimental animal data obtained at high doses to the low exposures predicted in humans. The linearized multistage (LMS) model is frequently... 

As a result, to date epidemiological studies of pesticide exposures have only been indicative of the presence of elevated health risks. Quantitative studies contributing to evidence on exposure-response relationships which could be used for quantitative risk assessment purposes are not widely available. This implies that the epidemiological potential has not been explored to its limits, as has been done for certain other agents such as asbestos and lead, for which present legislation has been based, to a large extent, on quantitative evidence of health risks in humans obtained from epidemiological studies. 

The conclusion in the case study is that neither occupational exposure nor environmental exposure to atrazine and simazine is likely to produce adverse health consequences in the United States population. This conclusion is based on a quantitative risk assessment which estimated that human intakes of atrazine and simazine are much smaller than the intakes required to produce adverse health effects in animal experiments. 

In the US, quantitative risk assessments are conducted for carcinogenicity. The risk assessment is performed by multiplying the chronic dietary exposure estimate by the qi. ... 

In the United States, some state and federal regulatory agencies conduct quantitative risk assessments on known or suspect carcinogens for continuous or long-term human exposure by extrapolating downward in linear fashion from an npper confidence limit on theoretical excess risk (FDA 1985 EPA 1986). The values derived for a specified acceptable theoretical excess risk to the U.S. human population, based on a lifetime of exposure to a carcinogenic substance, have been used extensively for regulatory purposes. 

As an example of a quantitative risk assessment we will consider angina attacks caused by CO-exposure. The model for the quantification is given in Fig. 8. 

EPA recommends three approaches (1) if the toxicity data on mixture of concern are available, the quantitative risk assessment is done directly form these preferred data (2) when toxicity data are not available for the mixture of concern, data of a sufficiently similar mixture can be used to derive quantitative risk assessment for mixture of concern and (3) if the data are not available for both mixture of concern and the similar mixture, mixture effects can be evaluated from the toxicity data of components. According to EPA, the dose-additive models reasonably predict the systemic toxicity of mixtures composed of similar (dose addition) and dissimilar (response addition) compounds. Therefore, the potential health risk of a mixture can be estimated using a hazard index (HI) derived by summation of the ratios of the actual human exposure level to estimated maximum acceptable level of each toxicant. A HI near to unity is suggestive of concern for public health. This approach will hold true for the mixtures that do not deviate from additivity and do not consider the mode of action of chemicals. Modifications of the standard HI approach are being developed to take account of the data on interactions. 

The traditional scientific and political response to these data gaps has been to collect more information and use a technique called quantitative risk assessment to calculate the probability of harm given particular exposures, applying numerous assumptions in the process. While this process has been termed the sound science approach, it is often far from that. Quantitative risk assessments often narrow the types of information that go into decision-making and hide uncertainties. They are time-consuming and costly to complete and while debates over details of these assessments occur, the default policy option is that no policy action is necessary. 

Kuzmack, A. M., and McGaughy, R. E. (1975). Quantitative Risk Assessment for Community Exposure to Vinyl Chloride. U.S. Environmental Protection Agency, Washington, D.C. 

The initial step in using key events in an MOA framework is a quahtative one, as described in Table 13.2, namely to match the key events for a particular chemical with those for a particular MOA (DNA-reactivity in Table 13.2). However, it is also possible to utilize key events to develop informative biomarkCTs of exposure and effect as well as bioindicators of disease outcome that can be utilized in a quantitative risk assessment process. 

In summary, having established an animal MOA and human relevance for this MOA, it is appropriate to address dose-response assessment, human exposure analysis, and risk characterization. Thus, the purpose of the human relevance framework is to establish which chemicals (or chemical mixtures) should be considered for a quantitative risk assessment and which do not require further consideration because they present a minimal risk or no risk to humans. Several thoroughly worked examples are presented in Meek et al. (2003). 

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