Appendix D - Dossier (PDF) - Tera

date: 20–JUL–2005
5. Toxicity Substance ID: 71–43–2
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overall 12–fold increase in total micronuclei.
DNA probe assays showed no consistent, significant increase
in hyperploidy at chromosomes 8 and 14, although values from
treated animals were typically slightly higher than control.
Combining results for the two probes and the two cell types
again showed a significant, weak, dose–related increase in
frequency of hyperploidy (15% in controls, 25% in high dose
mice). The percentage of mononuclear cells was slightly
decreased in benzene–treated animals, but this was
significant only in the 100 mg/kg bwt/d group.
LONG–TERM (12 WK) BENZENE TREATMENT
The frequency of micronuclei in newly–formed PCEs from
benzene–treated mice increased from 2% in control to 75% in
animals given 400 mg/kg bwt over 12wk, while the frequency
in NCEs increased from 2% to 26%. There was a significant
decrease in the PCE:NCE ratio (controls = 1.2; 0.5 in
high–dose group).
Probes for the mouse major and minor satellites showed an
increase in micronuclei originating from chromosomal loss
(26–fold increase at 400 mg/kg bwt/d) as well as micronuclei
arising from breakage of the mouse heterochromatin (17–fold
increase) and euchromatin (16–fold increase) against an
overall 17–fold increase in total micronuclei. At the
highest dose (400 mg/kg bwt/d), chromosomal breakage was
responsible for approx. 87% of the total micronuclei.
DNA probe assays for chromosomes 8 and 14 generally failed
to detect significant increases in hyperploidy. Combining
results for the two probes and the two cell types lead to a
significant increase in hyperploidy in bone marrow cells
from treated mice (12% in controls, 20% in high dose mice).
The percentage of mononuclear cells decreased from 45% in
controls to 35–32% (significant) in mice given 100 or 400
mg/kg bwt/d over 12 wk.
Source: A.K. Mallett Surrey
Conclusion: Results from these experiments suggest that benzene causes
both chromosomal breakage and aneuploidy in mouse bone
marrow cells. Chromosomal breakage is the predominant effect
and occurred primarily within euchromatin. Aneuploidy was
relatively infrequent, with increases of both chromosome
loss and hyperploidy being observed.
26–JAN–2003 (319)
Appendix D: Benzene SIDS Dossier
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