(VCCEP) Tier 1 Pilot Submission for BENZENE - Tera

6.1.12e Conclusions
Based on a recent review of all available scientific evidence, it is not possible to reach definitive
conclusions regarding human developmental and/or reproductive toxicity of benzene. Relevant
studies were severely limited by small populations of subjects, poorly defined or missing
exposure information (including exposure to other confounding chemicals), as well as recall and
selection bias. Most epidemiology studies evaluating the potential relationship between
benzene and reproductive/developmental toxicity are case control studies. Case-control
studies, while useful tools for generating hypotheses, rarely provide reliable quantitative
exposure data. As a result, it is not possible to use data from most case-control studies in a
quantitative risk assessment.
Reproductive epidemiology presents quite a challenge to investigators, in both study design and
conduct. Many of the endpoints of interest (e.g., menstrual cycle abnormalities or spontaneous
abortions) are relatively common occurrences in the human population. This fact compounds
the difficulties faced by investigators attempting to establish environmental or occupational
causes for reproductive endpoints. Additional confounders, such as diet, genetics, and lifestyle
factors all likely play a role in the background incidence of these events. As such, without
careful control of these confounder factors, appropriate interpretation of any data collected is
greatly complicated.
These and other shortcomings in the available data have been reviewed by several
organizations, including the ATSDR, the US EPA and the European Union (EU). To date, no
federal regulatory agency or scientific body has established a regulatory toxicity value for
benzene based on the reproductive or developmental toxicity in humans. The data are not
robust enough for such a determination. The Organization for Economic Cooperation and
Development (OECD) reviewed the EU risk assessment and concluded:
"Evidence from human data for an effect of benzene exposure on female reproduction is
not sufficient to demonstrate a causal association due to poorly designed studies and
inadequately quantified exposure to benzene as well as to other chemicals.
Epidemiological studies in males on effects on fertility are not available. Likewise
epidemiological studies implicating benzene as a developmental toxicant have many
limitations thus not providing sufficient information to assess the effects on the human
fetus." (OECD, 2005)
As described herein, there are poorly documented studies that are suggestive of an association
between un-quantified benzene exposures and maternal toxicity in the form of menstrual
alterations. Additionally, there are both positive and negative studies on the potential adverse
effect on the human fetus following parental exposure to benzene, including spontaneous
abortion, low birth weight or specific malformations. While leukemia studies are consistent in
their demonstration that parental exposure to benzene is not casually related to the
development of ALL, there is limited evidence for a potential association with childhood AML
(which has not been independently evaluated). Problems and short-comings inherent in the
specific studies preclude the development of a causal relationship between these reported
adverse effects and benzene exposure. In the absence of additional, more reliable data, it is
not currently possible to conclude that parental benzene exposure will adversely affect the
developing fetus (including the development of AML) or adversely effect reproductive function in
either exposed parent.
Benzene VCCEP Submission
March 2006
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