(VCCEP) Tier 1 Pilot Submission for BENZENE - Tera

follow-up of this same cohort, Wong et al. (1999) evaluated 18,000 petroleum distribution
workers (including professional drivers and marine loading workers) exposed to gasoline
containing 2%–3% benzene. These authors estimated that the cumulative lifetime exposure to
benzene could be as high as 128 ppm-years and 8000 ppm-years total hydrocarbons (THC),
including peaks. The average employment duration was 26 years. Risks of total leukemia,
acute myeloid leukemia, multiple myeloma, and kidney cancer were examined. Total lymphatic
and hematopoietic cancers were significantly decreased in this cohort, with an SMR of 0.69.
There was no increased risk of developing AML observed in this cohort.
Many small case-control studies have been conducted, with inconsistent results. Some studies
report small increases, and others report decreased or no excess risk (Siemiatycki et al., 1987;
Jakobsson et al., 1993; Grandjean et al., 1991; Brandt et al., 1978).
Automobile mechanics constitute another occupational group that is exposed to benzene,
primarily though exposure to gasoline (Hotz et al., 1997). There is considerable epidemiological
literature available to evaluate the occupational risk of developing AML in automobile
mechanics. A large-scale cancer survey was conducted by Williams et al. (1977) and found no
increased risk of AML, ALL, CML, or ALL associated with automobile mechanics or gas station
attendants. Loomis and colleagues conducted a case-control study and examined ANLL and
leukemia rates in mechanics and service station attendants (Loomis et al., 1991). The number
of eligible subjects was 615,843. The odds ratio (OR) for ANLL in ‘motor mechanics’ and
‘service station attendants’ was 0.8 (95% CI: 0.5–1.1). One study was found that reported an
elevated SMR for all leukemias combined in car mechanics, fuel attendants, and painters
exposed to ‘high’ levels of fuels and solvents (Hunting et al., 1995). The elevated SMR was
based on only three leukemia cases (and only one was AML).
Collectively, the literature does not support the hypothesis that mechanics have an elevated risk
of developing AML (Hotz and Lauwerys, 1997; Jarvisalo et al., 1984; Linos et al., 1980; Linet,
1988; Howe et al., 1983; Jacobs et al., 1993; Giles et al., 1984; Mele et al., 1994)
6.1.12 Other Human Data
6.1.12a Genotoxicity
Benzene is an established etiological factor in the development of AML in humans. Additionally,
benzene is carcinogenic in multiple experimental animal species via all major routes of
exposure. Consequently, considerable research has been undertaken to understand the
mechanism of action for benzene induced carcinogenicity. This includes an extensive
evaluation of possible genotoxic mechanisms for benzene and/or its reactive metabolites. Over
250 individual publications containing original data on the genotoxicity of benzene were found in
the literature. Nonetheless, there is still uncertainty regarding the genotoxic potential of
benzene and its metabolites with inconsistent as well as contradictory results reported. This
variability could be the result of methodological differences, choice of metabolites, exposure
conditions or a variety of other poorly defined factors. This inconsistent dataset complicates any
attempt to generate a clear hypothesis regarding the role that genotoxicity plays in benzene
induced animal or human carcinogenicity.
All standard genotoxicity tests in mammalian (including human) cells have been conducted for
benzene and its reactive metabolites (see Section 6.2.2 for further discussion on animal
genotoxicity). These include a variety of assays designed to measure DNA reactivity and
adduct formation, micronuclei formation, clastogenicity (including chromosomal aberrations and
Benzene VCCEP Submission
March 2006
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