Case study cumulative exposure

A worktable that can be used to calculate a cumulative exposure estimate on a site-specific basis is provided in Table 2. To use the table, environmental levels for outdoor air, indoor air, food, water, soil, and dust are needed. In the absence of such data (as may be encountered during health assessment activities), default values can be used. In most situations, default values will be background levels unless data are available to indicate otherwise. Based on the U.S. Food and Drug Administration s (FDA s) Total Diet Study data, lead intake from food for infants and toddlers is about 5 pg/day (Bolger et al. 1991). In some cases, a missing value can be estimated from a known value. For example, EPA (1986) has suggested that indoor air can be considered 0.03 x the level of outdoor air. Suggested default values are listed in Table 3. 

EPA released the first case study of cumulative risks from 24 OPs in food for scientific review in mid-2000. Public comments were solicited and several scientific panel (SAP) meetings were held on various aspects of EPA s quantitative methods. In December 2001 a preliminary OP-CRA (cumulative risk assessment) was released, this time encompassing 30 OPs, additional foods, more residue data and all major routes of exposure. Public comments were solicited again and another series of SAP meetings were held. The revised final OP-CRA was issued in June 2002 after more than 20 SAP meetings and four rounds of public comment (US Environmental Protection Agency, 2002). It is the most sophisticated and data-rich pesticide risk assessment ever carried out. 

Two of the more interesting uses of pharmacokinetic data in risk assessment involve the neurotoxic agents lead and methylmercury (Chapter 4). In the case of lead, epidemiological studies have typically involved the development of quantitative relationships between levels of lead in the blood and adverse health effects. Other measures of lead in the body have also been used. Levels in blood are now very easy to measure, and they do carry the strong advantage that they integrate cumulative exposures from many possible sources (water, food, paint, soil, air, consumer products). Current public health targets for lead are expressed as blood concentrations, typically in pg/dL (Chapter 4). 

A case-cohort study of aluminum production plant workers showed a clear excess of lung cancer risk in men who had worked in Soder-berg potrooms in jobs with high exposure to CTPV, and that the risk was not due to confounding by smoking. The rate ratio for lung cancer rose with cumulative exposure to CTPV measured as benzene-soluble material to 2.25 at 10-19 mg/m -years benzene-soluble matter but did not rise with further exposure. 

Eisen et al (1994) USA Nested case-control of laryngeal cancer 108 fatal and incident cases 538 controls (study base Eisen et al., 1992 cohort) 1941-84 Cumulative exposure to straight and soluble types of metalworking fluid and metalworking fluid particulate exposure during grinding duration of exposure to metalworking fluid and other components. 

Castorina, R., A. Bradman, T.E. McKone, D.B. Barr, M.E. Harnley, and B. Eskenazi. 2003. Cumulative organophosphate pesticide exposure and risk assessment among pregnant women living in an agricultural community A case study from the CHAMACOS cohort. Environ. Health Perspect. 111(13) 1640-1648. 

The methodology in the case study for chronic exposure, as well as several advances in probabilistic assessment methodology for acute exposure (e.g., a person s exposure on a single day), are being incorporated into the Cumulative and Aggregate Risk Evaluation System (CARES) begun in 2000 and being further developed with the International Life Sciences Institute (ILSI) in 2004. 

CHARACTERIZING DOSE AND RISK IN A CUMULATIVE ASSESSMENT 277 CASE STUDY 280 Case Study Defining Risk 280 Case Study The Dose-Response Relationship 280 Case Study Using the Margin of Exposure to Characterize the Risk 281 Case Study Benchmark Doses 282 Case Study Margins of Exposure 284... 

A fairly detailed case study illustrating a probabilistic approach to both aggregate and cumulative assessments is described in the first part of this chapter. This case study focuses on chronic exposure (that is, a person s long-term average dose). The case study was prepared as part of a submission to the US Environmental Protection Agency (USEPA) in 1996. 

Another difficulty arises from the use of cumulative exposure (the product of exposure duration x intensity) as a surrogate exposure metric in the available studies. Finkelstein (1995) noted that the use of cumulative exposure requires the assumption that duration and intensity are equally important in determining the effective dose. Finkelstein further noted that if exposure estimates are inaccurate or inconsistently measured (which can be the case for many retrospective epidemiology studies), a finding of a statistically significant association between cumulative exposure and a health outcome can mislead one in having confidence in an apparent exposure-response relationship that is principally influenced by duration of exposure and not by exposure intensity. 

Using a predictive model developed from mesothelioma data from studies of asbestos insulation workers (Peto et al. 1982), asbestos textile workers (Peto 1980), amosite factory workers (Seidman 1984), and asbestos-cement workers (Finkelstein 1983), EPA (1986a) estimated that continuous lifetime exposure to air containing 0.0001 f/mL of asbestos would result in about 2-3 cases of mesothelioma per 100,000 persons. The corresponding cumulative lifetime exposures associated with excess risks of 10 " -10 are shown in Figure 3-1. Cumulative exposure levels of 0.031, 0.0031, 0.00031, and 0.000031 f-yr/mL represent excess mesothelioma risks of 10" , 10 , 10, and 10 ", respectively. Appendix D provides further details on the derivation of these risk estimates. Currently (in 2001), EPA is in the process of reviewing their cancer risk estimates for asbestos fibers. 

Both chronic human studies and animal studies proved the causal relationship between cumulative UVR exposure and skin cancer (277), particularly non-melanoma skin cancer (NMSC). The link between the two is also evident from the fact that NMSC is most common on the head, neck, arms, and hands (278, 279). In particular, the correlation between UVR exposure and SCC seems to be very strong. Cutaneous SCC of the head and neck occurs almost exclusively on areas receiving maximal exposure (269,280). The link between BCC and cumulative exposure to UVR is not as evident (270, 281). Although BCC occurs on the face, head, and neck, unlike SCC, its distribution does not correspond well with the areas that receive maximum sun exposure (269). Case-control studies indicated that cumulative sun exposure is the most important risk factor for SCC, whereas inability to tan was the most important risk factor for BCC (270,282,283).Subsequently, it has been suggested that, for BSC, intermittent sun exposure, particularly in the childhood, may be more important than cumulative exposure (282). 

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