(VCCEP) Tier 1 Pilot Submission for BENZENE - Tera

estimate is very conservative both because of the conservative nature of the model and
because it did not consider workplace administrative management controls. Benzene
exposures from human milk were similar to that from other food sources except that from highend
occupationally exposed mothers, which were higher.
Exposures to benzene from gasoline were assessed for in-vehicle, refueling and small engine
use scenarios. Published literature provided data for analysis of the in-vehicle and refueling
scenarios.
Benzene exposure from tobacco smoke was assessed for ETS and mainstream smoking.
Emission rates of benzene from cigarettes were used in an EPA indoor air model to calculate
indoor air concentrations due to ETS. The model estimated that ETS adds slightly less than 1
µg/m3 to the background indoor air levels. Benzene exposures from mainstream smoking were
calculated using the published emission rates from cigarettes and the common inhalation dose
algorithm. Mainstream smoking resulted in doses similar to that of typical occupational
exposures in the benzene manufacturing and production industries.
The exposure assessment indicated that the inhalation pathway is the primary route of exposure
with systemic (absorbed) doses at least one order of magnitude higher than those received via
oral ingestion or dermal pathways, except for infant ingestion of human milk from an
occupationally exposed mother. Of the ambient background sources, inhalation of indoor air
contributed approximately 95% of the overall dose to children and prospective parents. Food
and water accounted for the remaining 5%. For nursing infants of occupational exposed
mothers up to 22% of the overall infant’s dose is estimated to be from benzene concentrations
in human milk, though this estimate is likely to be very conservative given the model used and
the typical practice of removing nursing mothers from benzene exposed jobs.
Risk Assessment
The risk assessment evaluates of the potential for age-related differences in the sensitivity
towards benzene induced toxicity. In the absence of good relevant animal models for AML and
with no child-specific epidemiology data on benzene, an alternate analysis is provided to
address whether children are more sensitive to benzene induced hematopoetic toxicity or AML
than adults. This alternative analysis was based on the literature describing children’s
therapeutic treatment with chemotherapeutic agents that can cause AML and hematopoetic
toxicity. Chemotherapeutic agents (alkylating agents and topoisomerase II inhibitors) are known
to cause AML secondary to the treatment regimen in a clear dose-response manner. The
clinical data on leukemia risk associated with the treatment of primary pediatric cancers do not
indicate that children are at increased risk of developing chemically induced AML. Likewise,
published data on the myelosuppressive/hematotoxic effects of various chemotherapy agents in
children and adults do not support the existence of an age related difference in sensitivity.
Therefore, additional uncertainty/safety factors were not used to adjust the benzene reference
values used in this risk assessment.
The EPA default (linear) approach of calculating HQs and excess cancer risk contains
significant conservatism, as EPA acknowledges. The use of a single value for the HQ and/or
CSF would inappropriately convey a level of confidence or certainty about the risk estimates,
when in fact, the HQ and excess risk predicted using a single point estimate contain a large
degree of uncertainty, and usually reflect, as with EPA’s benzene Integrated Risk Information
System (IRIS) values, the upper end of the conservative range of uncertainty. To fully evaluate
the range of potential risks, a range of RfDs and cancer slope factors were used to provide
Benzene VCCEP Submission
March 2006
6