Appendix D - Dossier (PDF) - Tera

date: 20–JUL–2005
5. Toxicity Substance ID: 71–43–2
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cases of myeloid leukemia in CD–1 mics and a marked
depression was observed in marrow and spleen cellularity.
The concentration and number of marrow and spleen CFU–S and
marrow GM–CFU–C were also depressed. The number of splenic
GM–CFU–C were also reduced, however, splenic GM–CFU–C
concentration was increased relative to control. Stem cell
depletion seems, therefore, to be involved in the
pathogenesis of benzene–induced hematotoxicity.
Source: Deutsche Shell Chemie GmbH Eschborn
06–JAN–1997 (440)
Type: other: Hematotoxicity
Remark: Benzene (BZ) and Hydroquinone (HQ) were shown to induce
granulopoiesis in a mouse model and in the murine diploid,
interleukin (IL)–3–dependent, G–CSF–inducible, myeloblastic
cell line, 32DcI3(G). We show that granulocyte–colony
stimulating factor (G–CSF) can provide both a proliferative
and differentiative signal for myeloblasts whereas BZ, HQ
and LTD4, a G–CSF–induced effector essential for
granulocytic differentiation, can replace G–CSF for
differentiation, but cannot obviate the IL–3 requirement
forgrowth and survival. HQ and LTD4 synergize with IL–3 to
promote a significant stimulation of proliferation. An
analysis of the kinetics of stage–specific granulocytic
differentiation induced by these agents over 6 days in the
absence of IL–3 demonstrated that all of the inducers
causedvirtually complete differentiation. G–CSF promoted
predominantly terminal differentiation. BZ, like LTD4,
showed a stimulation of all stages of progenitors as well
asterminally differentiated granulocytes but with a delayed
onset because BZ must induce the formation of LTD4. In
contrast, HQ induced differentiation which arrested at the
myelocyte stage.
Source: Deutsche Shell Chemie GmbH Eschborn
06–JAN–1997 (489)
Type: other: Hematotoxicity
Remark: Pregnant Swiss Webster mice were exposed from Day 6 through
Day 15 of gestation to either air, 5 ppm, 10 ppm, or 20 ppm
benzene. On Day 16 of gestation, 2 days after birth, and 6
weeks after birth, progeny of the exposed dams were assayed
for the amount and type of hemoglobin produced and for
recognizable hematopoietic cells in the peripheral blood
andhematopoietic organs. None of the benzene exposures
inducedsignificant changes in the indices assayed from the
16–day fetuses. In contrast, 2–day neonates exposed in
utero to all concentrations of benzene exhibited reduced
numbers of circulating erythroid precursor cells. In
addition, those 2–day neonates exposed in utero to 20 ppm
benzene exhibited increased numbers of hepatic hematopoietic
blast cells and granulopoietic precursor cells accompanied
by decreased numbers of erythropoietic precursor cells.
Six–week adult mice exposed in utero to 20 ppm benzene
Appendix D: Benzene SIDS Dossier
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