The committee concludes, from its review of the epidemiologic literature, that there is inadequate/insufficient evidence to determine whether an association exists between exposure to the solvents under review and multiple sclerosis.

Alzheimer’s Disease and Solvent Exposure: Epidemiologic Studies

Alzheimer’s disease (AD), a neurodegenerative disease marked by progressive impairment in cognition and memory, is described earlier in this chapter. The committee evaluated five studies: three from the United States (Graves et al., 1998; Kukull et al., 1995 and Shalat et al., 1988), one from Canada (CSHA, 1994), and one from Australia (Gun et al., 1997) (Table 7.12).

All studies, which were case-control, included cases based on the criteria of the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer Disease and Related Disorders Association criteria for the diagnosis of AD (McKhann et al., 1984). This diagnostic scheme distinguishes between possible, probable, and definite AD. Definite AD can be diagnosed only pathologically through biopsy or at autopsy. Three of the studies included only probable AD, one included possible AD (Gun et al., 1997), and one (Shalat et al., 1988) did not state whether subjects with possible AD were included. Cases for four studies were recruited from medical-care settings; the other study (CSHA, 1994) recruited cases with recent onset (within 3 years) previously identified in a population-based prevalence study.

Two studies were based on the AD registry of Group Health Cooperative, a large health maintenance organization in Seattle, Washington. The first was by Kukull and colleagues (1995), and the later study (Graves et al., 1998) was restricted to a subset of cases from the Kukull et al. (1995) study for whom a spouse was available to serve as a proxy informant. That strategy was adopted to enhance the accuracy of job information. The controls in both studies were a random sample of patients from the same Group Health Cooperative from which the AD registry recruited cases. Controls were frequency-matched on age and sex, and they were included if they achieved a score of more than 28 of a possible 30 on the Mini-Mental Status Examination, a test of cognitive function. Job-history information was obtained at interview about exposure to five classes of solvents: aromatic hydrocarbons, chlorinated solvents, ketones, fuels, and alcohols.

Kukull and colleagues (1995) reported an association between occupational solvent exposure and AD in men. When exposure was defined as “exposure to any solvent” in one of the five classes, the study found, in men only, an adjusted OR of 6.3 (95% CI=2.2–18.1). The adjusted odds ratio for both sexes was not significant. The authors speculate that underreporting by controls may have resulted in the findings of the higher association in men. When solvent exposure was defined differently, through job descriptions of four solvent-related occupations, the adjusted OR for the association between what was termed probable solvent exposure and AD was 1.8 (95% CI=1.1–3.1).

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