Appendix D - Dossier (PDF) - Tera

date: 20–JUL–2005
5. Toxicity Substance ID: 71–43–2
______________________________________________________________________________
chromosomes was performed per sample.
Haematopoietic cytotoxicity
The frequency of myeloid progenitor cells (colony forming
units–granulocytic macrophage; CFU–GM) was quantified using
a cytokine–enriched proprietary assay (Methocult ^TM).
Statistics
Student’s t–test was used to compared CFU–GM frequencies.
Aneusomy frequencies were compared using chi–square test,
with Cochran’s test to identify any dose–response
relationship present.
Result: Effects on haematopoiesis
Blood and marrow cellularity of control and benzene–treated
mice were similar at all measurement intervals (i.e 6 d, 9
wk and 8 mo post–treatment). The frequency of
primative/immature cells with the Lin–minus c–kit+ Sca–1+
phenotype and marrow CFU–GM was similar in control and
benzene–treated mice, indicating minimal direct toxicity on
immature haematopoietic cells.
Aneusomy in haematopoietic sub–populations
The frequency of circulating lymphocytes and marrow myeloid
and hsc–containing sub–populations with copy changes in
chromosomes 2 and 11 were quantified 6 d, 9 wk and 8 mo
post–treatment. In benzene–treated mice, the frequency of
aneuploid lymphocytes and myeloid cells was higher at 9 wk
than at 6 d, suggesting disruption of chromosomal
segregation in differenting cells and/or progenitors. About
8 mo after benzene treatment, approx. 14% of cells with the
Lin–minus c–kit+ Sca–1+ phenotype exhibted numerical
chromosomal aberrations affecting chromsomes 2 or 11.
Source: A.K. Mallett Surrey
Conclusion: The results indicate that large oral doses of benzene induce
copy changes in chromosomes present in immature/primitive
cells, and that these changes persist for several months.
However the contribution of benzene–induced aneuploidy in
immature/primitive cells to leukemogenesis remains to be
determined.
25–APR–2002 (413)
Type: other: aneuploidy in oocytes
Species: mouse Sex:
Remark: Chinese language article, translation unavailable:
Appendix D: Benzene SIDS Dossier
ABSTRACT:
"Mice were treated with various doses of benzene (942,
1,881 and 3,762 mg/kg respectively) via single gavage and
multiple inhalation (706, 1,922 and 4,864 mg /m3,
respectively). After gavage, the mice were pair–matched
(1:1) with males overnight. The ovulated oocytes and the one
cell zygotes were collected for cytogenetic analysis
and the frequencies of aneuploidy were detected.
The frequencies of aneuploidy in M II oocytes significantly
– 516/957 –