Appendix D - Dossier (PDF) - Tera

date: 20–JUL–2005
5. Toxicity Substance ID: 71–43–2
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intointernal doses, and these internal doses are used in
conjunction with a multistage model to compare previous
estimated virtually safe doses (VSD) associated with small
added health risks. The ratio of VSD for the administered
dose risk assessment to the VSD from the internal dose risk
assessment was approximately 1.0 for the F344/N rats and
ranged from 2.5 to 5.0 for B6C3F1 mice in the National
Toxicology Program study. For an occupational exposure of
1ppm, a risk estimate of 0.7 excess cancers/1000 exposed
withan upper bound 3.5/1000 was obtained for a total
metabolite internal dose risk assessment.
Source: Deutsche Shell Chemie GmbH Eschborn ;German rapporteur
Flag: Risk Assessment
14–SEP–2000 (65)
Type: Metabolism
Remark: Cancer risk from exposure to benzene for a working lifetime
was estimated from data obtained in studies with rodents.
Cancers of the Zymbal gland and the blood–forming system
were selected as endpoints for the assessment because of
their consistent occurrence. The combined metabolites were
judged from toxicological data to be the best
representativeof the reactive agent. Because of similarity
in the percentages of lifetime exposed in the rodent studies
and inthe occupational setting, the amount metabolized/day
as a result of exposures 5 days a week for a lifetime was
judged to be an appropriate dose paradigm for this
assessment. Derived Michaelis–Menton constants were used to
convert the doses of combined metabolites from the
pharmacokinetic studies to the doses used in the bioassays.
Scaling across species was based on allometric
relationships. Experimentaldata were used to scale doses
across species with body weight ratios raised to the
exponents of 0.74 for the inhalation route and 1.0 for the
oral route. The occupational lifetime cancer risk estimated
from rodent datawas 6 to 14 cases/1000 workers, which is
consistent with the9.5 to 174 leukemia cases/1000 estimated
by others from epidemiological data.
Source: Deutsche Shell Chemie GmbH Eschborn
06–JAN–1997 (91)
Type: Metabolism
Remark: A physiological pharmacokinetic model for benzene,
incorporating metabolic transformations, is used to explore
why benzene, but not phenol is carcinogenic at many sites
inrats. The model has been parametrized using in vitro or
in vivo experimental data. Ranges, rather than fixed values
were assigned to the parameters. The model–predicted
levelsof phenol and hydroquinone in the tissue are
consistently higher when phenol, rather than benzene, is
administered. This result demonstrates that the
differential carcinogenicity of the two compounds is not
explainable in the context of this pharmacokinetic analysis.
Appendix D: Benzene SIDS Dossier
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