Appendix D - Dossier (PDF) - Tera

date: 20–JUL–2005
5. Toxicity Substance ID: 71–43–2
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high incidence of antibodies against Hsp71 (approximately
40%) which was associated with a decrease in white blood
cells [3.84±1.13 x 10(9)versus 7.68±1.84 x 10(9) in
controls] and with an increase in activities of serum SOD
(138.43±23.15 micro/ml) and lymphocyte DNA damage (18.7%).
These data suggest that antibodies against Hsps can
potentially be useful biomonitors to assess if workers are
experiencing or have experienced abnormal xenobiotic–induced
stress within their living and working environment.
Source: EXXON Biomedical Sciences East Millstone, NJ
Reliability: (2) valid with restrictions
21–JUL–2000 (1283)
Type: other: Overview of the toxicology of benzene.
Remark: No abstract given in paper.
Source: ExxonMobil Biomedical Sciences Inc. Annadale, New Jersey
13–FEB–2002 (1106)
Type: other: Possible mechanisms of carcinogenesis after exposure
to benzene.
Remark: This review covers the history of the toxicology of benzene,
current exposure levels, the metabolism of benzene,
reactions of the metabolites with biomolecules, and possible
mechanisms of carcinogenesis due to benzene. Epidemiological
evidence indicates a relationship between exposure to
benzene and the occurrence of acute non–lymphocytic
leukaemia in humans. Working groups convened by IARC and
other organizations have therefore judged that there is
sufficient evidence for classifying benzene as a human
carcinogen. Despite much research, including numerous
studies in animals, the detailed mechanism of the
carcinogenicity of benzene is unknown. The significant
differences in the responses of rodents and humans to
benzene are not understood. Benzene forms many metabolites,
some of which are reactive towards biomolecules, but the
metabolite(s) responsible for the induction of leukaemia is
unknown. Candidate metabolites, either singly or in
combination, include epoxides, oxepins, quinones and
aldehydes, all of which are reactive towards proteins and
DNA. Our studies on muconaldehydes and benzene oxide–oxepin
are discussed in this context. The significance of DNA
adduct formation in respect of human leukaemia is uncertain.
The overall reactivity of benzene towards DNA has been shown
to be very low in experimental animals, although
dose–related reactivity of metabolites with DNA was
observed. The lack of significant DNA reactivity is
reflected in the lack of activity of benzene in short–term
tests for genotoxicity; however, benzene causes oxidative
stress, which can be detected as oxidative damage to DNA.
Mechanisms other than DNA damage may play a role in
benzene–related toxicity, e.g. reactions of benzene
metabolites with essential enzymes such as topoisomerase II.
Source: EXXON Biomedical Sciences East Millstone, NJ
Appendix D: Benzene SIDS Dossier
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