Exposure proxies

EXPOSURES RELEVANT TO HEALTH THE CONCEPTUAL FRAMEWORK 246 Considerations of Exposure Timing 246 Considerations of Exposure Route 247 Practical Context of Pesticide Exposure 248 EPIDEMIOLOGICAL STUDY DESIGNS AND EXPOSURE ASSESSMENT 248 Prospective Cohort Studies 248 Retrospective Cohort Studies 249 Case-Control Studies 250 Cross-Sectional Studies 252 EXPOSURE ASSESSMENT STRATEGIES 252 INFLUENCE OF THE ACCURACY OF EXPOSURE PROXIES ON MEASURES OF ASSOCIATION 254 Errors in Qualitative Proxies 254... 

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. 

INFLUENCE OF THE ACCURACY OF EXPOSURE PROXIES ON MEASURES OF ASSOCIATION... 

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. 

Epistemic uncertainty —missing knowledge—is due to a lack of information that through R D you could buy directly or estimate through proxy methods, if you so chose. These are controllable risks, although in practice they may be unduly expensive to control relative to the risk exposure (threat x likelihood). 

Questions about accuracy can also arise from the use of measurement data collected for one purpose that are used for another. For example, investigators and governments often rely on general area sampling of airborne contaminants from fixed monitoring stations in a metropolitan area as a proxy for exposures of individuals. However, numerous factors may affect the accuracy of this assumed relationship (e.g. the locations of the monitors, the mobility of the individuals with respect to the monitors over time, presence of other sources that affect the monitors but not the individuals, exposures of the individual in the workplace or elsewhere that are not picked up by the area monitors). 

Exposure data varies in quality across epidemiological studies, especially those concerned with environmental exposures. Many earlier epidemiological studies relied exclusively on self-reported or proxy exposures (e.g., residence). For example, a study of the effect of... 

Targets would be based on use-specific volumes as a proxy for human and environmental exposures, occupational health statistics, industry performance indicators, emission registers or other benchmarking schemes. 

The route of exposure is another aspect of exposure in which health-relevance must be considered. In Section One of this book, there is a detailed discussion of exposure assessment methodologies, including the importance of identification of the most prevalent route of exposure (dermal, inhalation or oral) and the necessity of knowing the absorption of the pesticide to allow calculation of the absorbed dose for risk assessment. For epidemiological purposes, exposure-assessment smdies are usually limited to assessing contact exposure levels. Since dermal absorption is not known for many pesticides or complex mixtures, uptake through the dermal route can often not be estimated and contact exposure data are a poor proxy of internal exposure (absorbed dose) (Schneider et al., 1999). 

Although it is difficult to generahze, the validity of qualitative proxies of exposure can be very poor in some cases. Tielemans et al. (1999a) recently compared... 

To better evaluate pollution prevention options, the project attempted to assess the risks posed to individuals and populations exposed to chemical contaminants released from the refinery. An initial risk assessment analysis was performed to identify chemicals requiring further study, and to establish a baseline by which to judge potential risk reduction opportunities. Since change in exposure to benzene was used as a proxy for evaluating relative risk reductions associated with alternative pollution prevention options, the usual uncertainty associated with risk assessments was not a factor in the option analysis. The uncertainty in absolute risk assessments can arise from multiple sources the use of animal study results, difficulties with human studies, variation in individual responses to chemical exposures, the impact of differing dose rates, multiple simultaneous exposure to chem-... 

The ranking analysis discussed in the remainder of this section used benzene exposure at a nearby residence as a proxy for the risk associated with population exposure to refinery releases. In Table X, the share each option represents of the total benzene exposure reduction achieved by implementing all options is given in the column labeled Benzene exposure reduction. The barge loading option accounts for 55% of the benzene exposure reduction attributable to all options. In cost-effectiveness terms, the cost for a 1% benzene exposure reduction ranges from 9000 for secondary seals to 1.48 million for upgrading the wastewater treatment plant. 

Considering simplifying rules of thumb, safety factors, default values, or proxy indicators of exposures and effects when information is lacking. 

Understanding how people are exposed to soil contaminants is fundamental to any study investigating a possible link with health. That said, most health and epidemiological studies fail to appreciate, or identify, if and how people are exposed. For example, many studies of communities around landfill sites simply use proximity to the site of interest as a proxy measure of exposure. Often such an approach is unavoidable, as there may be insufficient data to allow for a proper exposure assessment. While this approach has some merit, the lack of a proper exposure assessment will mean that the outcomes of the study (whether positive or negative) will be significantly weakened. 

For every case, controls were randomly selected from all children without malformations born on the nearest following day in the same study area. All cases and controls were geographically located with the address or postcode of the mother s place of residence, with an accuracy of 100 m, and residence was used as a proxy for exposure to chemical contaminants from the landfill site. 

In South Wales, the Welsh Combined Centres for Public Health compared indices of health in a population living near a landfill site with a population matched for socioeconomic status and examined environmental monitoring data.28 Using odour complaints as a proxy for exposure in five wards near the site, the authors compared mortality, rates of hospital admission and measures of reproductive health (proportion of all births and stillbirths of infants weighing... 

Researchers argue about the effects of prenatal exposure to PCBs on brain development and later childhood cognitive performance. Some studies find effects and some don t. Some studies do not involve direct measurements of PCBs in blood but rely on surrogate (proxy) measurements, such as consumption of fish from contaminated waters. It s also difficult to locate a population in which fetuses have been exposed to PCBs but not to other toxins. It may be that cognitive effects are limited to certain kinds of brain-work not revealed by current tests. We don t know yet. But given all the evidence that exists about serious effects in animals and human adults, and given the general axiom that the human fetus is about a hundred times more vulnerable than adults to toxins, it s reasonable to say that the question of the effects of prenatal exposure to PCBs is not yet resolved. 

Pu-Xe dating. Decay of Pu can be used as a chronometer of the first 100 Ma for some specific meteorite parent bodies. Both Pu and the LREE tend to be concentrated in refractory minerals like phosphates. Which LREE is the best proxy for Pu Various authors have suggested Nd (Lugmair and Marti 1977), Sm (Jones and Burnett 1987), or Pr or Ce (Boynton 1978). There are no neutron-induced reactions that produce a rare gas from any of the LREE, but all of these, particularly Nd, do produce the light xenon isotopes like Xe and Xe through cosmic-ray-induced spallation reactions (Wider 2002, this volume). In fact, in many cases, the LREE (and presumably Pu), are probably not fractionated much from each other. Hence, if the cosmic ray dose (i.e., the cosmic ray exposure age) is known, and the production rate of isotopes like " Xe and Xe is also known, then the abundance of the LREE can be calculated. Then the ratio of Xe244 (Pu-... 

Bonner MR, Han D, Nie J et al (2005) Breast cancer risk and exposure in early life to polycyclic aromatic hydrocarbons using total suspended particulates as a proxy measure. Cancer Epidemiol Biomarkers Prev 14 53-60... 

Adjusted for age, yearly income, cultural origin, proxy status, smoking, occupational exposure to asbestos, silica, arsenic, cadmium, and chromium. 

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