Appendix D - Dossier (PDF) - Tera

date: 20–JUL–2005
5. Toxicity Substance ID: 71–43–2
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CFU–HPP/femur was observed at 1, 2, 4 and 8 weeks (200 ppm)
and 2, 4 and 8 weeks (100 ppm), and in the number of
CFU–HHP/5x10(4) marrow cells at 2, 4 and 8 weeks (100 and
200 ppm). An investigation of recovery of the CFU–HPP
population in mice following a 4–week exposure demonstrated
that the number of CFU–HPP/femur and number of
CFU–HPP/5x10(4) marrow cells approach control levels within
11 (100 ppm) and 18 (200 ppm) days.
Source: Deutsche Shell Chemie GmbH Eschborn
06–JAN–1997 (951)
Type: other: Hematotoxicity
Remark: The hematopoietic cell response to benzene intoxication in
mice (during and after long–term inhalation) was analyzed
bya mathematical model of murine hematopoiesis. Two
complementary methods, Time–Curve and Steady–State
Analysis,were developed to identify target cells for benzene
toxicityand to quantify the extent of damage in different
stages of development of these target cells. Erythropoietic
cells were the most sensitive; (ii) granulopoietic cells
were about half as sensitive as erythropoietic and (iii)
hematopoietic stem cells exhibited a sensitivity that
rangedbetween that of erythropoietic and granulopoietic
cells. A dose–response relationship between benzene levels
and damagein target cells (valid from 1 to more than 900
ppm) was derived that was linear for doses up to 300 ppm and
plateaued thereafter. This relationship indicated that
benzene–induced hematotoxicity is subject to a saturable
process. Recovery of hematopoiesis following chronic
benzene intoxication was simulated for different doses and
preceding exposure periods. The impaired recovery
followingexposure periods > 8 weeks could be explained by a
severe reduction in the maximum self–maintenance of stem
cells.
Source: Deutsche Shell Chemie GmbH Eschborn
06–JAN–1997 (1012)
Type: other: Hematotoxicity
Remark: Using the 59Fe uptake method of Lee et al. it was shown
thaterythropoiesis in female mice was inhibited following IP
administration of benzene, hydroquinone, p–benzoquinone,
andmuconaldehyde. Toluene protected against the effects of
benzene. Coadministration of phenol plus either
hydroquinone or catechol resulted in greatly increased
toxicity. The combination of metabolites most effective in
reducing iron uptake was hydroquinone plus muconaldehyde.
We have also shown that treating animals with benzene leads
to the formation of adducts of bone marrow DNA as measured
by the 32P–postlabeling technique.
Source: Deutsche Shell Chemie GmbH Eschborn
06–JAN–1997 (1078)
Appendix D: Benzene SIDS Dossier
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