Quantitative exposure assessment

If actual or potential exposure has been identified, a quantitative exposure assessment is necessary. Exposure levels/concentrations for each potentially exposed population need to be derived from the available measured data and/or from modeling. A range of exposure values to characterize different subpopulations and scenarios may result. These results are taken forward to the risk characterization where they are combined with the results of the effects assessment in order to decide whether or not there is concern for the human population exposed to the substance. In some cases all three types of exposure estimates may contribute to an overall exposure value (combined exposure), which should be considered in the risk characterization. 

Baker, D.B. and R.P. Richards (1990). Herbicide concentrations in Ohio s drinking water supplies A quantitative exposure assessment. In D.L. Weigmann, ed., Pesticides in the Next Decade The Challenges Ahead. Proceedings of the Third National Research Conference on Pesticides. November 8-9, Virginia Water Resources Research Center. Blacksburg, VA Virginia Polytechnic Institute and State University, pp. 9-30. 

Damiano J. 1995. Quantitative exposure assessment strategies and data in the Aluminum Company of America. Appl Occup Environ Hyg 10 289-298. 

Currently, there are only a few cases where biomarkers can be used for quantitative exposure assessment. Biomarkers can be used to indicate that a person has been exposed and that the chemical has been absorbed into the body. They can often be used to rank exposure among individuals. Biomarkers alone cannot provide information on the source, route, or duration of exposure. Even with these limitations, biomarkers, when appropriately validated, can effectively be used to evaluate trends in these exposures (CDC, 2005) and determine the effect of exposure mitigation strategies as well as predict target tissue dose. 

First, this chapter will describe a conceptual framework to illustrate the special challenges posed because exposures assessed for epidemiologic studies must be relevant to the health outcome under investigation. Secondly, some of the most commonly applied epidemiological study designs will be introduced, with special emphasis on exposnre assessment issnes associated with the design. Thirdly, some widely applied exposure assessment approaches will be introduced, ranging from qualitative classifications of exposure to quantitative exposure assessment of pesticide concentrations. The influence of measurement error on measures of association between exposure and disease, such as the slopes of exposure-response relationships and risk or odds ratios, will be briefly reviewed. Finally, exposure proxies used in case-control studies of chronic effects of pesticide exposure will be reviewed and the concepts introduced earlier will be applied. 

Quantitative exposure assessment is possible by measuring the external exposure in air or on skin, or by measurements of biological markers in serum, urine, fat or other relevant body fluids. 

The accuracy of exposure assessment is determined by systematic and random errors in the assessment. For quantitative exposure assessments, important sources of error include measurement errors (i.e. from laboratory and field monitoring techniques), as well as variations in exposure over time and space. For qualitative exposure proxies (e.g. self-reported past exposures, occupational histories or expert evaluations), the most important sources of error are recall bias (systematic differences in exposure recall between cases and controls) and random error, expressed in terms of intra- and inter-rater agreement. Although systematic errors can result in serious misinterpretations of the data, especially due to scaling problems, random errors have received more attention in epidemiology because this type of error is pervasive, and its effect is usually to diminish estimates of association between exposure and disease. The magnitude of random errors can be considerable in epidemiological field studies. 

Despite the fact that few epidemiological studies with quantitative exposure assessment data are available for pesticide exposure, more insight is now present on how the optimal exposure assessment strategy might look. In particular, the use of determinants of exposure studies, as reviewed recently, and their application in health-based exposure estimation, seems a promising approach that can solve many of the problems associated with pesticide exposure assessment in agriculture. This approach will be of use in both occupational and domestic epidemiological studies on this topic. 

A recent study examined the exposure-response relationship between biomass combustion and ARI in children of rural Kenyan households [41]. This was preceded by rigorous quantitative exposure assessments in the same households [22]. Quantitative exposure assessments are therefore crucial for the development of exposure-response relationships and greatly facilitate subsequent health risk assessments. 

Blair, A., and Stewart, P. A. (1992). Do quantitative exposure assessments improve risk estimates in occupational studies of cancer Am J Ind Med 21, 53-63. 

Risk Characterization. Once a quantitative exposure assessment has been made, Risk Assistant allows the user to automatically calculate lifetime excess cancer risk and/or a hazard index for toxic non-carcinogenic effects of chronic exposure for any agent included in the toxicity databases which currently include about 300 compounds. The appropriate hazard values (slope-potency factors and reference doses) for the relevant routes of exposure are automatically retrieved from the databases. The uncertainty calculations in the exposure assessment can also be retrieved to assess the range of risks associated with a given exposure situation. 

The results of the quantitative exposure assessment are taken forward to the risk characterisation where they are combined with the results of the effects assessment. 

Exposure assessment, step three, allows a risk assessor to estimate the significance of the effects induced by high doses of a chemical in experimental animals in a human situation. Exposure assessment is, in fact, a prerequisite for quantitative risk assessment because it allows a comparison between effects induced by high dose with those induced by low doses, and also allows... 

Altliough the technical conununity has come a long way in understanding how to do a better job in luizard identification, dose-response assessment, and exposure assessment portions of risk assessment, it lias only begun to understand how to best cluiractcrize hcaltli risks and how to present tliese risks most appropriately to both the public and decision makers. Tlie next tliree sections specifically address tlicse issues. Tliis section deals witli qualitative risk assessment while tlie next two sections deal witli quantitative risk assessment. 

Risk characterization is tlie process of estimating tlie incidence of a healtli effect under tlie various conditions of human or animal exposure as described in the exposure assessment. It evolves from both dose exposure assessment and toxicity response assessment. The data are then combined to obtain qualitative and quantitative expression of risk. 

Exposure assessment is the qualitative and/or quantitative estimation of the probable intake of a biological, physical, or chemical agent through food, and exposme from other relevant sources. Only intakes of toxicologically significant amounts can lead... 

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. 

Exposure assessments have become an essential element of contemporary risk assessment (NAS/NRC, 1983). The primary purpose of exposure assessment is to qualitatively and/or quantitatively determine exposure and absorbed dose associated with a particular use practice or human activity. Contemporary exposure assessors and risk managers place a high premium on accurate data obtained by monitoring chemical exposure scenarios and critical human activities or work tasks. 

The risk characterization procedure will result in a quantitative comparison per substance of the outcome of the exposure assessment and of the effects assessment. This comparison is made through the ratio PEC/PNEC. The generic name for PEC/ PNEC in EUSES is risk characterization ratio (RCR). Other ratios are used in EUSES for the risk characterization such as the margin of safety (MOS) or the ratio of the estimated no-effect or effect level parameter to the estimated exposure level for human subpopulations and the acceptable operator exposure level (AOEL). 

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 the final phase of risk analysis—risk characterization—one integrates outputs of effects and exposure assessments. Risk is expressed in qualitative or quantitative estimates by comparison with reference values (e.g., hazard quotient). The severity of potential or actual damage should be characterized with the degree of uncertainty of risk estimates. Assumptions, data uncertainties and limitations of analyses are to be described clearly and reflected in the conclusions. The final product is a report that communicates to the affected and interested parties the analysis findings (Byrd and Cothern, 2000). 

---