(VCCEP) Tier 1 Pilot Submission for BENZENE - Tera

quantification of benzene air concentrations provided and potential confounders were not
adequately addressed.
Taken collectively, the data linking benzene exposure to male or female reproductive toxicity is
insufficient to allow scientifically tenable conclusions to be reached. Available evidence
suggests that the complex occupational exposures that occurred in these studies may have
potentially contributed to the menstrual abnormalities in some women. However, co-exposures
with other chemicals, genetics, various lifestyle factors and other potential confounders prevent
a definitive link with benzene from being established. More importantly, inadequately
characterized exposure histories make it impossible to establish concentrations of benzene;
therefore, it is not clear how this information could be used for quantitative risk assessment
purposes. Additionally, historic exposures, particularly in some Chinese industries (such as
shoe-making), are considerably higher than those experienced in the US under current
occupational practices.
6.1.12c Human Developmental Toxicity of Benzene
A few studies have attempted to address the potential association between benzene exposure
and developmental toxicity. Some of these studies have suggested that benzene exposure may
be associated with spontaneous abortions and developmental toxicity in the fetus, but this
literature is highly inconsistent. Due to its lipophilic nature and relatively small molecular weight,
benzene readily crosses the placenta and has been measured in cord blood at levels equal to or
exceeding maternal levels (Dowty et al., 1976). Therefore, it is assumed that maternal
exposure would likely result in some benzene reaching the developing fetus.
Forni et al. (1971) published the first case report of a woman exposed to benzene during her
entire pregnancy. Benzene exposures were high enough to have resulted in severe
pancytopenia, but did not adversely affect the fetus (Forni, 1971). A 1972 Russian study
reported evidence of fetal toxicity and premature interruptions of pregnancy in women exposed
to gasoline and chlorinated hydrocarbons (Mukhametova, 1972). Due to this complex exposure,
it was not possible to attribute this reported toxicity solely or even partially to benzene. Another
study reported increased chromosomal aberrations in the lymphocytes of children whose
mothers were exposed occupationally to benzene and/or organic solvents compared to nonexposed
controls (Funes-Cravioto et al., 1977). The relevance of peripheral cytogenetic
findings is not clear nor is it clear if this affect was causally related to maternal benzene
exposure. Benzene levels were not quantified, and it is not possible to rule out confounding
chemical exposures.
A 1984 study of pregnant laboratory employees was conducted to evaluate the potential
association between occupational exposures and pregnancy outcome (Axelsson et al., 1984).
There was no difference in miscarriages, perinatal death rates or prevalence of malformations
between those with mixed solvent exposure (some recalled specifically using benzene) and
those without. However, the lack of reliable exposure information, potential recall bias and
complex chemical exposures, weaken the relevance of this study for risk assessment purposes
(Axelsson et al., 1984). Savitz, et al. (1989) analyzed data from three case groups of pregnancy
outcome and reported a slight, but statistically significant increase in the risk of stillbirths
associated with paternal exposure to benzene (OR = 1.5, 95% CI = 1.1-2.3). Benzene levels
were not quantified, and it is not possible to rule out confounding chemical exposures (Savitz et
al., 1989). Strucker et al. (1994) evaluated the relationship between paternal benzene exposure
and spontaneous abortions and found no evidence of an effect at benzene air concentrations
greater than 5 ppm (Strucker et al., 1994). Xu et al. (1998) conducted a retrospective
Benzene VCCEP Submission
March 2006
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