inasmuch as exposures were attributed by industrial hygienists unaware of the status of subjects. The committee did not believe that any of these studies were subject to strong confounding biases, in that risk factors for brain and other CNS cancer are not well known. A dose-response relationship between brain and other CNS cancers and increasing levels of exposure was supported by two studies: Heineman et al., 1995; Ireland et al., 1997. However, the study by Hayes and colleagues (1996) did not yield a dose-response relationship based on years of exposure to benzene, nor did the nested case-control study by Carpenter and colleagues (1988) support an association with brain or other CNS cancers. Moreover, several studies were based on small numbers of exposed cases. As a result, the committee did not reach a consensus. Some committee members believed that the evidence was limited/suggestive of an association; others believed it was inadequate/insufficient to determine whether an association exists. Additional research will help to clarify whether an association exists between exposure to benzene and the risk of brain and other CNS cancers.

All but one of the studies reviewed by the committee reported positive associations between exposure to solvent mixtures and brain and other CNS cancers, including two that showed a slight dose-response pattern (Heineman et al., 1994, 1995). However, the studies did not examine the same cancer outcomes; some evaluated only brain cancer, others looked at brain and other CNS cancers together, and still others evaluated specific subtypes of brain cancer. Furthermore, the mixtures of solvents were known in some studies and unspecified in others. Given those concerns and the consistently positive findings, the committee could not reach a consensus; the evidence was neither wholly inadequate/insufficient to determine whether an association exists nor wholly limited/suggestive.

Table 6.32 identifies the key studies and relevant data points reviewed by the committee in drawing its conclusions. Unless indicated in the tables, the study populations include both men and women.

The committee concludes, from its assessment of the epidemiologic literature, that there is inadequate/insufficient evidence to determine whether an association exists between chronic exposure to the solvents under review, other than benzene, and brain or other central nervous system cancers.

TABLE 6.32 Selected Epidemiologic Studies—Brain and Central Nervous System Tumors and Exposure to Organic Solvents


Study Population

Exposed Cases

Estimated Relative Risk (95% CI)


Cohort Study—Incidence

Anttila et al., 1995

Biologically monitored workers in Finland



Entire period since first measurement


1.09 (0.50–2.07)


0–9 years




10–19 years


2.00 (0.86–3.93)


20+ years


0.76 (0.02–4.26)

Cohort Studies—Mortality

Boice et al., 1999

Aircraft-manufacturing workers in California, potential routine exposure


0.54 (0.15–1.37)

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