Although a number of studies of the effects of exposure to solvents, particularly ethylene glycol ethers, on hematologic parameters were reviewed, the studies did not provide information on the persistent, long-term health effects of concern in this report (e.g., Cardoso et al., 1999; Cook et al., 1982; Cullen et al., 1983, 1992; Kyvik et al., 1992; Shamy et al., 1994; Shih et al., 2000; Welch and Cullen, 1988).

Summary and Conclusion

The hematotoxicity of benzene’s metabolites has been well characterized in animal studies with strong evidence of a dose-response relationship. For more than a century, case studies have reported a direct association between chronic high-level exposure to benzene and aplastic anemia in humans. This association has been confirmed in studies of workers exposed to potentially high concentrations of benzene that found consistently increased risks of aplastic anemia (Table 9.2). The effects of low-level benzene exposure, however, have not been studied as fully, and there have been inconsistent findings regarding changes in hematologic parameters in studies of low level occupational exposure to benzene. Studies of exposure to solvent mixtures have not revealed consistent increased associations with aplastic anemia.

Results are for cases with higher exposure as compared with hospital controls. The committee concludes, from its assessment of the epidemiologic and experimental literature, that there is sufficient evidence of a causal relationship between chronic exposure to benzene and aplastic anemia.

There is inadequate/insufficient evidence to determine whether an association does or does not exist between exposure to other specific organic solvents under review or solvent mixtures and aplastic anemia.

TABLE 9.2 Selected Epidemiologic Studies: Aplastic Anemia and Exposure to Organic Solvents



Exposed Cases

Estimated Relative Risk (95% CI)


Cohort Studies

Paci et al., 1989

Shoe-manufacturing workers in Florence, Italy









15.66 (5.47–32.64)a

Yin et al., 1996

Workers in China



Linet et al., 1989

Residents of Baltimore, Maryland


3.1 (1.0–9.2)


Case-control Studies

Issaragrisil et al., 1996

Residents of Thailand



Bangkok residents


4.6 (2.5–8.7)

Guiguet et al., 1995

Residents of France



All types of solvents


0.9 (0.5–1.7)c


Halogenated solvents


1.3 (0.6–2.7)c


Hydrocarbon solvents


1.2 (0.6–2.3)c

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