(VCCEP) Tier 1 Pilot Submission for BENZENE - Tera

which were lower than the Paustenbach estimates. The upper bound of this unit risk range is
2.5×10 -2 at 1 ppm (7.8×10 -6 at 1 µg/m 3 ). EPA recommends using the range of risk estimates,
each with equal scientific plausibility. Crump also calculated an estimated range of unit risk
based on a combination of models selected, disease endpoints, and exposure estimates. This
range was large; 8.6×10 -5 to 2.5×10 -2 at 1 ppm (3200 µg/m 3 ) (Crump and Allen, 1984).
EPA states that risk estimates would likely fall in the lower range if a sub-linear exposure
response model were found to be more plausible. EPA further concluded that the shape of the
dose-response curve cannot be considered without a better understanding of the biological
mechanism of benzene-induced leukemia (U.S. EPA, 2000). This remains uncertain and as a
result, EPA’s default public-health-protective approach is to use the linear extrapolation model
(U.S. EPA, 2000).
EPA’s quantitative oral unit risk estimate is an extrapolation from the known inhalation dose
response to the potential oral route of exposure. The inhalation unit risk range is converted to
an oral slope factor, which is expressed in units of risk per µg/kg/day. The inhalation-to-oral
conversion assumes a standard air intake of 20 m 3 /day, a standard body weight of 70 kg for an
adult human, and 50% inhalation absorption. The drinking water unit risk was then calculated
from the oral slope factor, assuming a drinking water intake of 2 L/day. For benzene, the range
of EPA’s oral slope factors was determined to be 1.5×10 -2 to 5.5×10 -2 per (mg/kg)/day. The
drinking water unit risk has a corresponding range of 4.4×10 -7 to 1.6×10 -6 per (µg/L).
6.1.7.2 Additional Literature for Cancer Effects
The scientific and medical literature has the leukemogenic potential of chronic exposure to high
concentrations of benzene. The following is a brief compilation of some of the more important
studies on benzene carcinogenicity in humans.
Aksoy at al. (1974) reported the effects of benzene exposure among 28,500 Turkish shoe
workers. Peak exposures were estimated to be as high as ~600 ppm. There was a significant
elevation of leukemia or ‘pre-leukemia’ (likely MDS) observed when compared to the general
Turkish population. This cohort was followed up in 1980, and eight additional cases of leukemia
were reported (Aksoy, 1977; Aksoy and Erdem, 1978). While the Turkish shoe worker studies
are consistent with the wider literature on AML and benzene, the study lacks detailed exposure
information and a well-defined comparison population.
Ott et al. (1978) observed a non-significant increase in leukemia among 594 chemical workers
exposed to benzene. Air concentrations in this study were estimated to be from less than 2 to
over 25 ppm. Bond et al. (1986) updated this study and added an additional 363 exposed
workers. The overall risk of leukemia was non-significant, but the risk for myelogenous
leukemia was significantly elevated (SMR = 2.5). Unfortunately, the authors do not state
whether the observed myelogenous leukemia cases were acute or chronic. Estimated
cumulative exposures for workers in this study were reported to be 18–4211 ppm-months.
Wong (1983 and 1987a,b) reported on the mortality of 4602 male chemical workers. Dosedependent
increases were seen in the risk of leukemia (all types) and the biologically arcane
category of lymphatic and hematopoietic cancers combined. Cumulative exposure to benzene
at 60 ppm-years or greater exhibited a borderline significant risk of lymphatic and hematopoietic
cancers. However, none of these cancers were myelogenous. These authors stated that,
based on these data, the cumulative, not peak, exposures were the best predictor of cancer
risk.
Benzene VCCEP Submission
March 2006
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