(VCCEP) Tier 1 Pilot Submission for BENZENE - Tera

The National Cancer Institute (NCI) and the Chinese Academy of Preventative Medicine
conducted an epidemiology study of over 74,000 benzene-exposed Chinese workers employed
from 1972 to 1987 (Yin et al., 1987, 1989, 1996; Travis et al., 1994; Hayes et al., 1997).
Workers came from a total of 672 Chinese factories and were employed in the painting, printing,
footwear, rubber, or chemical industries. A statistically elevated risk of all hematological
malignancies was observed with air concentrations of benzene less than 10 ppm, although a
meaningful dose response was not evident (Hayes et al., 1997). The risk of ANLL and a
combination of MDS and ANLL were not statistically elevated at less than 10 ppm benzene. At
higher exposure levels (10–25 ppm), the risk of ANLL and MDS increased to a statistically
significant level. Other leukemias (CML) were not significantly elevated at any exposure level.
These authors also reported an increased risk of developing NHL at greater than 25 ppm
benzene. At cumulative exposures estimated to be less than 40 ppm-years, there was no
elevated risk of ANLL or MDS/ANLL (Hayes et al., 1997). Cumulative exposures were 40–99
ppm-years before a positive association was reported with ANLL or MDS/ANLL risk. The
NCI/CAPM study was severely limited by the inclusion of concurrent exposures and the lack of
reliable exposure information. Further, significant confounders in NHL etiology were not
adequately accounted for. As a result, EPA does not view this data set as suitable for
quantitative risk assessment (U.S. EPA, 2000).
Recently, Glass et al. (2003) published findings from the 11th Australian Health Watch and
reported a significant increase in ANLL associated with benzene exposure. In this study, the
authors report a significant elevation of ANLL at cumulative benzene exposures of greater than
8 ppm-years (estimated value is not reported). These authors state that they find no evidence
of a threshold for ANLL. The reported cumulative exposures associated with a statistically
elevated risk were much lower than those similar industries from other countries. As a result,
these findings are inconsistent with the wider scientific and medical literature on ANLL risks
associated with benzene exposure, including an update of this overall cohort published by Gun
et al. (2004). Other methodological problems decrease the potential usefulness of this study for
risk assessment purposes. Some investigators believe that the expected cases of ANLL in the
baseline or control group in this study were under-represented. This would change the
calculated risks, as well as the interpretation of this data, particularly at low exposures
(Schnatter, 2004; Goldstein, 2004). There are also problems with case selection and controlling
for various types of bias (Schnatter, 2004; Goldstein, 2004). As it stands, this study may
suggest a relationship between benzene exposure and ANLL; however, a stronger interpretation
regarding exposures is not possible.
6.1.8 Ongoing Studies
Two large epidemiology studies are concurrently being conducted in and around Shanghai,
China. Shanghai was chosen for these studies, because it has a large population base (over
17 million), as well as numerous industries and factories where benzene exposures are still a
significant occupational health hazard. Both of these independent studies are designed to
further characterize the relationship between benzene exposure (in various industries) and
hematopoietic and lymphoid malignancies.
The first study is a follow-up and extension of the NCI/CAPM study that began in the 1980s (Yin
et al., 1987, 1989, 1996; Travis et al., 1994; Hayes et al., 1997). The likely goal of this
investigation is to extend the follow-up period for study cohorts and to provide quantitative data
to better characterize the benzene exposures. Early reports from this investigation have been
discussed briefly (Lan et al., 2004).
Benzene VCCEP Submission
March 2006
46