(VCCEP) Tier 1 Pilot Submission for BENZENE - Tera

epidemiology study in Beijing, China to evaluate the potential relationship between
petrochemical exposures and spontaneous abortions. The OR for spontaneous abortions and
benzene exposure was statistically significant (OR = 2.5, 95% CI = 1.7 – 3.7). This data could
have been influenced by recall and selection bias as well as potential confounding chemical
exposures (Xu et al., 1998). Chen et al. (2000) reported that birth weight among children born
to benzene exposed workers in a petrochemical plant in Beijing was significantly reduced
compared to unexposed controls. Again, benzene exposures were not quantified and
confounding chemical exposure was likely (Chen et al., 2000).
Only one study was found that specifically addressed the relationship between parental
exposure to chemicals (including benzene) and malformations. Wennborg et al. (2005)
completed a survey of Swedish laboratory workers exposed during their pregnancy. The OR
ratio for neural crest malformations associated with benzene exposure was statistically
significant (OR = 5.3, 95% CI = 1.4-21.1) (Wennborg et al., 2005). Benzene exposures were
not quantified and exposure to confounding chemicals likely occurred. Further, this study was
based on an extremely small number of cases (major malformations was 2.3% in exposed and
1.9% in unexposed); therefore, misclassification of exposure or cases would have a significant
impact.
Epidemiology studies investigating the potential for benzene as a developmental toxicant have
many limitations. These include concomitant exposure to other chemicals, inadequate sample
size, lack of adequate quantification of exposure levels as well as biases associated with casecontrol
studies (recall, selection). Additionally, a variety of non-chemical confounders are also
potentially present including genetics and various lifestyle factors, such as diet, stress and
smoking history that are difficult to completely account for. Therefore, while there is limited
evidence suggesting that benzene exposures may increase the risk of spontaneous abortions or
malformations, the overall database on developmental toxicity in humans is currently insufficient
to draw definitive conclusions.
6.1.12d Parental Exposure to Benzene and the Development of Childhood Leukemia
Childhood AML is the second most common leukemia in children (next to acute lymphoblastic
leukemia or ALL) and represents about 20% of all cases of childhood leukemia (Colby-Graham
et al., 2003). Overall, the rate of childhood AML in the US is ~400 new cases per year and
unlike ALL, the rates do not fluctuate significantly with age (Bhatia et al., 1995; Lightfoot, 2005).
Understanding potential environmental causes of childhood AML has been particularly
challenging, mainly due to the rarity of the disease. There have been scattered reports
suggesting that maternal and/or paternal exposure to benzene or other chemicals could lead to
an increased risk of developing childhood AML. Recent studies have been specifically designed
to evaluate the potential relationship between parental exposure to benzene (and other
exposures) and the development of childhood leukemia in the offspring.
Shaw et al. (1984) conducted an early case-control study of childhood leukemia and paternal
occupation. No association between paternal exposures to benzene and childhood leukemia
(not specified) was observed. Maternal occupation was not considered. Exposures were not
quantified and were based on occupations listed on the child’s birth certificate (Shaw et al.,
1984). Shu et al. (1988) evaluated the relationship between parental occupational exposures
and childhood leukemia in Shanghai, China using a case control study design (Shu et al., 1988).
A variety of potential etiological agents were investigated, including benzene. Paternal
occupational exposure was not associated with either form of acute childhood leukemia (ALL or
ANLL). However, maternal exposure to benzene was positively associated with ANLL (OR =
Benzene VCCEP Submission
March 2006
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