broadly, acute leukemia, chronic leukemia, lymphatic leukemia, and hairy cell leukemia. The committee acknowledges that the literature on adult leukemia could be divided by specific cell type but believes that there were too few studies to support valid conclusions on each specific type of leukemia. The committee therefore determined that there were enough high quality studies to support conclusions regarding the broad category of adult leukemia and acute leukemia only, which includes acute myeloid leukemia (AML) and acute lymphocytic leukemia (ALL). The decision to group leukemia types by onset (acute vs chronic) rather than by cell type was based on the available literature. The studies on acute leukemia, including AML and ALL, appeared to share more risk factors and findings than the more limited literature on chronic myeloid leukemia (CML) and chronic lymphocytic leukemia (CLL). Thus, the literature directed the committee to draw conclusions of association that encompassed both subtypes of acute leukemia.

Description of Case-Control Studies

The characteristics of the case-control studies considered by the committee in drawing its conclusions of association are described below in Table 6.39. All but one case-control study (Aschengrau et al., 1993) included interviews with study subjects concerning occupational history. Several questionnaires also included queries about specific chemical exposures, including benzene, trichloroethylene, and tetrachloroethylene (Albin et al., 2000; Bernard et al., 1984; Clavel et al., 1996; Nordström et al., 1998; Richardson et al., 1992; Staines and Cartwright, 1993). In many studies, experts reviewed questionnaire responses and attributed exposures unaware of case or control status (Albin et al., 2000; Ciccone et al., 1993; Clavel et al., 1996, 1998; Costantini et al., 2001; Lazarov et al., 2000; Malone et al., 1989; Richardson et al., 1992). Another study used a job—exposure matrix (Clavel et al., 1998) to determine exposures. However, in some studies, self-reported exposures were used as the metric (Bernard et al., 1984; Clavel et al., 1995; Flodin et al., 1981; Mele et al., 1994; Nordström et al., 1998; Staines and Cartwright, 1993). Unlike most occupational studies of leukemia, the study by Aschengrau and colleagues (1993) assessed exposure to tetrachloroethylene on the basis of estimated concentrations in public drinking water in five towns of Cape Cod, Massachusetts. Case-control studies of leukemia and exposure to organic solvents that had reasonably good assessments of exposure and enough exposed cases include those by Albin and colleagues (2000), Clavel and colleagues (1996), Lazarov and colleagues (2000), Malone and colleagues (1989), and Richardson and colleagues (1992).

Epidemiologic Studies of Exposure to Organic Solvents and Adult Leukemia

Several large cohort studies provided evidence for evaluating the association between exposure to benzene and adult leukemia. The principal cohort studies included several occupational populations with estimated levels of exposure, including the Pliofilm workers (Crump, 1994; Rinsky et al., 1981, 1987), Chinese factory workers (Hayes et al., 1997; Yin et al., 1996a,b), US chemical workers (Bond et al., 1986; Ireland et al., 1997; Wong, 1987a,b), US and British petroleum-distribution and oil-refinery workers (Rushton and Alderson, 1981; Wong et al., 1993), and, in nested case-control studies, petroleum-distribution workers in Canada (Schnatter et al., 1996a,b) and the UK (Rushton and Romaniuk, 1997).



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