Skip to main content

Currently Skimming:

2 Methodological Considerations in Evaluating the Epidemiologic Literature on Cancer and Exposure to Trichloroethylene
Pages 25-57

The Chapter Skim interface presents what we've algorithmically identified as the most significant single chunk of text within every page in the chapter.
Select key terms on the right to highlight them within pages of the chapter.


From page 25...
... An example of how this chapter's guidance should be applied is provided in the committee's assessment of the epidemiologic literature on kidney cancer presented in Chapter 3, and should also be applied to other outcomes (see Chapters 3-8)
From page 26...
... At least three levels of health outcomes should be considered in assessing the human health risks associated with exposure to trichloroethylene: biomarkers of effects and susceptibility, morbidity, and mortality. Few known susceptibility biomarkers specific to trichloroethylene have been assessed in humans.
From page 27...
... . Because of the lack of numbers for specific types of tumors, in older cohort studies all lymphatic and hematopoietic neoplasms were grouped together instead of handled as individual types of cancer (such as Hodgkin's disease)
From page 28...
... counties showed a negative association with average concentrations of radon measured in the counties (Cohen and Colditz 1994) , whereas the individual case-control and cohort studies show positive exposure-response patterns (NRC 1988)
From page 29...
... Cross-sectional studies are rarely useful for studying cancer because of this issue and because of possible selection biases in the underlying cohort that provides the sources of the population (e.g., selection of study participants to assess the prevalence of kidney cancer that may be related to duration of cancer and also to exposure)
From page 30...
... 1998) ; and defining in advance rules to indicate exposure based on job and industry classifications (referred to as job exposure matrices)
From page 31...
... . Figure 2-1 shows the basic levels of exposure assignments that may result from an exposure assessment and how they are related.
From page 32...
... ; (3) potentially exposed subjects have at least a minimum amount of the agent present in personal samples (e.g., skin contamination)
From page 33...
... Care must be taken to recognize the potential for misclassification in different exposure settings. Epidemiologic Approaches to Population Exposure Assessment Exposure assessment uses a combination of approaches to answer two questions: (1)
From page 34...
... Cold dip tanks have a lower exposure potential, but they have a large surface area and removal of the pieces can carry solvent out. Small bench-top cleaning operations with a rag or brush and open bucket have the lowest exposure potential.
From page 35...
... ~1955-1968 Trichloroethylene Trichloroethylene Stoddard solvent, (poorly controlled, (replaced some trichloroethylene (replaced tightened in 1960s) Stoddard solvent)
From page 36...
... , only area samples; several analysis methods: Combustion, titrate total chlorine 1947-1954 ~20 mg/m3 Nonspecific, ±30% Add pyridine, colorimetric assay 1954-1962 ~20 mg/m3 Nonspecific, ±30% Inject in gas chromatograph for 1962-1973 ~1 mg/m3 Specific, analysis ±20% Davis Chlorinated hydrocarbons 1954-1978 ~20 mg/m3 Nonspecific, halide combusted; real-time data on ±30% meter breakdown products Dräger Air drawn through special tube 1959-1974 ~20 mg/m3 Nonspecific, tube (<1 min) , chlorinated hydrocarbons ±50% break down and react with dye, read the color Gas 300 mL of air collected (<1 min)
From page 37...
... A variety of dose metrics may be used to quantify or classify exposures for an epidemiologic study. They are summarized in Table 2-3 and include precise summaries of quantitative exposure, concentrations of biomarkers, cumulative exposure, and simple qualitative assessments of whether exposure occurred (yes or no)
From page 38...
... Longest job Job with Only one job contributes Problems with: most years to risk and enough Many jobs with exposure subjects in job have had Too few subjects with sufficient intensity and sufficient intensity and duration to increase risk. duration to increase overall No risk from jobs with risk.
From page 39...
... contact with had sufficient intensity Too few subjects with agent and duration to increase sufficient intensity and risk. duration to increase overall risk.
From page 40...
... Job-exposure matrices work best when exposures are common and intense. Job-exposure matrices are also developed in some cohort studies where data are highly detailed (Smith et al.
From page 41...
... Assigning "exposed" to a population is implicitly a quantitative assignment because it means exposure is not zero, but it does not also imply that increased risks are detectable. Biomarkers In some studies, exposure may be estimated by the concentration of a biomarker.
From page 42...
... Below some of the most common sources of error in exposure for epidemiologic studies are discussed. Qualitative Exposure Assignments The determination of the presence or absence of a particular chemical in a subject's immediate environment is the first step in any exposure assessment.
From page 43...
... Collecting data by interviewing long-term workers or area residents is a common way to obtain descriptive exposure data. These data are subject to all of the usual limitations of individual memories and biases in recall.
From page 44...
... In Chapter 3 and Appendix D, epidemiologic studies of kidney cancer are evaluated to illustrate the methodology by which this might be done; the evaluation showed that some studies were more informative and others less informative than the authors concluded. ComBining and evaluating ePidemiologiC data Strategies for Including Studies in the Risk Assessment for Exposure to Trichloroethylene and Cancer A full review of the literature should identify all published studies in which there was a possibility that trichloroethylene was investigated, even though results per se may not have been reported.
From page 45...
... according to whether subjects in the study were "ever exposed," the committee suggests attempting to group studies according to some index of exposure, in a stratified or other type of analysis. These recommendations are consistent with EPA's guidelines: For epidemiologic data to be useful in determining whether there is an associa tion between health effects and exposure to an agent, there should be adequate characterization of exposure information.
From page 46...
... (Should ballot counting be used, then appropriate statistical methods need to be used to calculate P values for the proportion of positive studies.) If one takes the reasonable point of view that results from studies should be viewed as meta-data, then a more reasonable approach is to provide detailed tables and figures that summarize the results, especially as related to some index of meta-exposure (see examples in Chapter 3)
From page 47...
... Implicit in this type of analysis is the assumption that the effects of differences in methods and exposure assessments are random and small. Thus, if a publication bias exists, one would expect to
From page 48...
... This analysis provided evidence supporting an association in the Tier I studies for exposure to trichloroethylene and increased risk of kidney cancer (relative risk [RR] = 1.7, 95% confidence interval [CI]
From page 49...
... than in other studies (see Chapter 3) , providing a plausible explanation for the unusually high relative risks for kidney cancer that were observed.
From page 50...
... It appears that the findings for kidney cancer may not have been homogeneous given the unusually large effect reported by Henschler et al.
From page 51...
... The community studies have more limited exposure assessments but, under some circumstances, they can provide useful information about risks of exposures in the community. Similar to Wartenberg et al., Kelsh et al.
From page 52...
... Use of the Hill Guidelines to Assess Causality Reviews of epidemiologic data may be qualitative or quantitative. Qualitative reviews have frequently relied on interpreting findings with the set of guidelines first proposed by Hill (1965)
From page 53...
... . As noted earlier in this chapter, the most common limitation of epidemiologic data for quantifying risk is the availability of high-quality exposure data to construct exposure-response models.
From page 54...
... Because metabolic enzymes vary across individuals, if the carcinogenic agent is a metabolite, then use of the biomarker will increase the variability in the exposure assignments for the subjects in each exposure group. In the case of trichloroethylene, several studies from Scandinavia used measurements of trichloroacetic acid in urine in national databases of workplace surveillance programs to identify exposed subjects for a cohort study of cancer risk (Tola et al.
From page 55...
... . Second, the estimates of trichloroacetic acid were not from the entire study time period, and the duration of exposure of study subjects was not known.
From page 56...
... . Because there are no studies with good exposure assessments for trichloroethylene, it is important to begin a prospective study on a suitable cohort that could provide the missing quantitative relationship between long-term trichloroethylene exposure and disease risk.
From page 57...
... If heterogeneity is found to exist then a thorough search should be made to determine whether there are any explanations for the heterogeneity, such as differences in population exposures. ­Fixed and random effects models should be fitted to the data.


This material may be derived from roughly machine-read images, and so is provided only to facilitate research.
More information on Chapter Skim is available.