Fang et al. exposure (Kamel et al. 2002, 2005) may be related to ALS risk. We found no relation- ship of ALS risk either to military service or to the occupational group farming, fishing, or forestry. Some previous studies have suggested that farming was related to ALS (Granieri et al. 1988; Gunnarsson et al. 1991; McGuire et al. 1997), but other studies found no relationship (Sutedja et al. 2007; Weisskopf et al. 2005a). Earlier studies on the relationship of military service to ALS risk also had inconsistent find- ings—some suggested a positive association, but others did not (Schulte et al. 1996; Sutedja et al. 2007; Weisskopf et al. 2005a, 2005b). Reasons for these inconsistencies are not yet clear. Different approaches for classification of occupations, lack of information on specific workplace exposures related to the occupations, and potential confounding or effect modi- fication by other risk factors are all possible Table 4. Self-reported workplace exposures and the risk of ALS by lifetime days of exposure.a No. of controls (n = 253) No. of cases (n = 109) OR (95% CI)b p-Value for trend Exposure days Oil-based paints 1–399 400–1,999 ≥ 2,000 Paint thinners 1–399 400–1,999 ≥ 2,000 Paint strippers 1–399 400–1,999 ≥ 2,000 Adhesive 1–399 Dyes or printing inks 400–1,999 ≥ 2,000 1–399 400–1,999 ≥ 2,000 1–399 400–1,999 ≥ 2,000 1–399 400–1,999 ≥ 2,000 1–399 400–1,999 ≥ 2,000 1–399 400–1,999 ≥ 2,000 1–399 400–1,999 ≥ 2,000 1–399 400–1,999 ≥ 2,000 1–399 400–1,999 ≥ 2,000 Insecticides 1–399 400–1,999 ≥ 2,000 1390 Cutting, cooling, or lubricating oils Gas, diesel fuel, motor or fuel oil Antifreeze or coolants Degreasers or cleaning agents Mineral spirits or white spirits Solvents (e.g., toluene or xylene) 14 14 7 14 10 15 9 3 6 10 11 13 13 16 6 11 7 23 11 14 29 8 4 11 14 17 26 6 5 9 6 10 10 8 27 66 16 6 6 Electrical or electronic equipment or machinery aIndividuals with missing information on a specific workplace exposure were excluded from the analysis of that expo- sure; individuals who did not report a specific exposure served as the reference group for that exposure; exposures with < 10 cases were not presented. bCalculated from logistic regression models; all models were adjusted for age (< 56, 56–65, and > 65 years), sex, area of residence (Boston metropolitan area, eastern Massachusetts, and rest of New England), smoking, and educational level. 7 3 4 9 3 8 5 3 4 6 7 8 5 6 9 4 5 9 5 2 9 7 3 3 5 4 2 1 10 16 14 17 10 0 16 36 9 2 4 1.1 (0.4–2.8) 0.4 (0.1–1.5) 0.8 (0.2–3.0) 1.5 (0.6–3.8) 0.6 (0.2–2.4) 1.0 (0.4–2.7) 1.5 (0.4–4.8) 2.5 (0.5–13.3) 1.1 (0.3–4.2) 1.4 (0.5–4.2) 1.9 (0.7–5.2) 1.2 (0.4–3.1) 1.0 (0.3–2.9) 1.0 (0.4–2.6) 4.0 (1.3–12.1) 0.8 (0.2–2.9) 3.6 (1.2–10.5) 1.8 (0.8–3.8) 1.0 (0.3–3.1) 1.5 (0.6–3.7) 0.9 (0.4–1.9) 1.5 (0.4–5.1) 1.0 (0.2–5.6) 1.7 (0.6–4.5) 1.1 (0.4–2.9) 0.4 (0.1–1.4) 1.3 (0.6–2.6) 1.8 (0.4–7.7) 2.4 (0.6–9.2) 1.0 (0.3–3.4) 0.6 (0.1–2.9) 0.3 (0.0–2.5) 2.1 (0.8–5.5) — 1.6 (0.8–3.3) 1.5 (0.8–2.5) 1.3 (0.5–3.2) 0.6 (0.1–3.4) 1.2 (0.3–4.8) 0.33 0.99 0.48 0.36 0.07 0.04 0.95 0.30 0.92 0.47 0.39 0.10 0.84 explanations. Using crude approximations of specific exposures—for example, military ser- vice—may account for some inconsistencies. That the association between military service and ALS may be time limited, as reported by another recent study (Horner et al. 2008), may also explain the different findings we have noted. “Farming” is also a general term not necessarily related to specific exposures. Earlier studies have suggested that sol- vents or other chemicals are associated with a higher risk of ALS, albeit without detailed information on any specific solvent or chemical (Chancellor et al. 1993; Chio et al. 1991; Gunnarsson et al. 1992; Morahan and Pamphlett 2006). Other studies did not confirm these suggestions (Gait et al. 2003; McGuire et al. 1997). Our study extends pre- vious work by considering specific solvents and chemicals. Workplace agents with poten- tial relations to ALS in our data included paint strippers; cutting, cooling, or lubricating oils; antifreeze and coolants; mineral or white spir- its; and dry cleaning agents. Specific chemicals responsible for these associations may include aliphatic chlorinated hydrocarbons, glycols, glycol ethers, and hexane. These associations with specific chemicals may also explain our findings for particular occupations. For exam- ple, precision metalworkers are likely exposed to metal particles and cutting, cooling, or lubricating oils. The fact that construction workers but not their supervisors had a higher risk provides further support for a role in ALS etiology of specific exposures that only the workers experienced. Several lines of evidence suggest bio- logical plausibility for the observed associa- tions between workplace exposures and ALS. n-Hexane, an organic solvent associated with a higher risk of ALS in our study, is a clas- sic neurotoxicant (Ritchie et al. 2001a) that caused polyneuropathy affecting both sensory and motor neurons (Chang 1990) and was associated with Parkinson’s disease (Canesi et al. 2003). Hydrocarbons were shown to induce persisting changes in protein expres- sion and neurotransmitter levels in the central nervous system and to impair neurobehavioral function in rats at the “real-world” concentra- tions experienced by human beings (Ritchie et al. 2001b). Acute intoxication with glycol ethers increased free-radical production in the nervous system in rats (Kadiiska and Mason 2000), and an acute oral challenge with ethyl- ene glycol in humans induced abnormal gait, loss of reflexes, central nervous system depres- sion, and convulsions (Hess et al. 2004). Our study did not find an overall asso- ciation between exposure to formaldehyde and ALS risk as reported earlier (Weisskopf et al. 2009), although we noted an imprecise 3-fold risk of ALS among the most highly exposed group (> 60,000 weighted exposure hr). These ovlume 117 | number 9 | September 2009 • Environmental Health Perspectives