All case-control studies of MDS reviewed included interviews with study subjects concerning occupational history, some of which yielded information on specific chemical exposures (Table 6.45). Some studies relied on expert review of questionnaire responses (Ciccone et al., 1993; Nisse et al., 2001; West et al., 1995, 2000) to determine exposures; assessments of exposure in other studies were based on self-reports (Goldberg et al., 1990; Ido et al., 1996; Mele et al., 1994; Nagata et al., 1999; Rigolin et al., 1998). Case-control studies of MDS and exposure to organic solvents that had reasonably good assessments of exposure and enough exposed cases include those by Nisse and colleagues (2001) and West and co-workers (1995).
Although several epidemiologic studies were used to examine the association between mixtures of organic solvents and MDS, in only one cohort study of Chinese workers occupationally exposed to benzene (Hayes et al., 1997), was MDS evaluated; however, cases of MDS were combined with cases of ANLL. An RR of 4.1 (95% CI=1.4–11.6) was observed, and the relative risk increased as average exposure to benzene increased (RR=3.2 for constant low-level exposure at under 10 ppm, 7.1 for constant high-level exposure at 25 ppm or higher). This was the first epidemiologic study to demonstrate an association between exposure to benzene and MDS and ANLL.
Earlier case series of benzene-exposed workers noted abnormalities in bone marrow and peripheral blood consistent with MDS specifically (Aksoy and Erdem, 1978; Goguel et al., 1967; Van den Berghe et al., 1979), but the recognition of this disease is relatively recent and has not always been considered in evaluating risks related to exposure to benzene.
Several studies examined the association between exposure to organic solvent mixtures and the risk of MDS. On the basis of qualitative and quantitative assessments of exposure by occupational experts, a study of 204 newly diagnosed cases of MDS and 204 sex- and age-matched controls (Nisse et al., 2001) assessed the association between exposure to solvents and the risk of MDS. Based on 43 exposed cases, the study observed a statistically precise OR of 2.6 (95% CI=1.6–5.4). That increased risk was supported by the other studies reviewed, including a study of 29 cases exposed to organic solvents (Rigolin et al., 1998) that found an OR of 7.11 (95% CI=2.42–20.88). Although those exposed to solvents had an increased risk (OR=7.11. 95% CI=2.42–20.88), those identified as painters, printers, shoemakers, and chemical-industry workers combined did not (OR=0.81, 95% CI=0.33–2.00). The study by Mele and colleagues (1994) found high odds ratios for shoemakers and painters individually (OR=4.3, 95% CI=0.9–21.1 and OR=5.4, 95% CI=0.5–61.0, respectively). The numbers of exposed cases were extremely small, as evidenced by the wide CIs, and the case definition of MDS included those with refractory anemia who had an excess of blasts; this made the health-outcome assessment less precise.
Studies by West and colleagues (2000) and Nagata and colleagues (1999) found increased risks of MDS among residents of the UK (OR=1.8, 95% CI=0.6–6.0) and Japan (OR =1.99, 95% CI=0.97–4.10), respectively. An earlier study in Japan (Ido et al., 1996) also showed increased risks of MDS in men and women exposed to organic solvents occupationally (OR=1.50, 95% CI=0.85–2.64).