(VCCEP) Tier 1 Pilot Submission for BENZENE - Tera

increased risk of disease. It should also be pointed out that this study is inconsistent with other
recent studies that found no alterations in peripheral blood cell counts in individuals exposed to
1 ppm benzene (Tsai, 2004). As described above, most of the existing literature (including
studies by many of these same authors) does not indicate hematotoxicity occurring at benzene
concentrations below 5-10 ppm.
Therefore, existing human data support that prolonged occupational exposure to high
concentrations of benzene (greater than 10–25 ppm) can result in peripheral cytopenias and
observable hematopoietic toxicity. However, there is much less consistency in the literature
regarding the potential adverse effects associated with low-dose exposure (less than 5 ppm).
6.1.7 Cancer
6.1.7.1 Critical Study for EPA’s Benzene Cancer Slope Factor (Rinsky et al. 1987)
The most important study of benzene and AML is the National Institute for Occupational Safety
and Health (NIOSH)–sponsored retrospective cohort mortality study of workers involved with the
manufacture of rubber hydrochloride (Pliofilm) at one of three plants in Ohio (Infante et al.,
1977; Rinsky et al., 1981, 1987). The original study evaluated 748 white male workers exposed
for at least 1 day in a rubber manufacturing facility. Exposure to benzene occurred in these
workers during 1940–1949. No effort was made to evaluate individual exposures to benzene
that could be used to help characterize a dose response relationship (Infante et al., 1977). In an
extension of this study, Rinsky et al. (1981) reported that all seven of the leukemias were of the
acute myelogenous type. This cohort was updated in 1987 and expanded to include 1165 nonsalaried
white male workers employed for at least 1 day through December 1965 (Rinsky et al.,
1987). Two additional AML cases were reported in this expanded cohort. Rinsky and coauthors
attempted to reconstruct cumulative exposures to benzene in terms of ppm-years for all
members of the expanded cohort and establish a dose-response relationship. The SMR for
AML was non-significant in the 0–39.99 ppm-years and the 40–199.9 ppm-year cumulative
exposure categories. At 200 ppm-year, the SMR for AML was 11.86, which was statistically
elevated. The last follow-up through 1996 reported five additional cases of AML with an SMR of
3.37, statistically elevated at the highest exposure category (Rinsky et al., 2002). All workers
with AML held jobs that first exposed them to benzene before 1950, and most of them before
1945 (Paxton et al., 1994, 1992). Few direct industrial hygiene data were available during this
time frame, so several attempts have been made to provide refined quantitative estimates for
the likely exposures that occurred during this time frame (Crump et al., 1984; Rinsky et al.,
1987; Paustenbach et al., 1992; Schnatter et al., 1996b).
The Rinksy (1981, 1987) study analysis of the ‘Pliofilm’ cohort was selected by EPA as the
critical study for dose-response analysis and for the quantitative estimation of cancer risk to
humans (Rinsky et al. 1981, 1987). This study was selected because it has ample power,
reasonably good estimates of exposure (except prior to 1946), a wide range of exposure from
low to high levels, and a relative lack of potential confounding chemicals. Further, the job
activities of the various workers were fairly well documented. Based on data obtained from this
cohort, the carcinogenic risk of inhaled benzene was calculated by EPA. Cancer risk is
expressed as the air unit risk and ranges from 2.2×10 -6 to 7.8×10 -6 as the estimated increased
risk for an individual who is exposed for a lifetime to 1 µg/m 3 benzene in air. The range was set
by the choice of exposure estimates used (Crump and Allen 1984; Paustenbach et al. 1992).
The lowest unit risk is based on the exposure estimates of Paustenbach (1992), because the
exposure estimates for the Rinsky cohort are the highest. That estimate is 7.1×10 -3 at 1 ppm
(2.2×10 -6 at 1 µg/m 3 ). The highest unit risk is based on Crump and Allen exposure estimates,
Benzene VCCEP Submission
March 2006
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