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Appendix D - Dossier (PDF) - Tera

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date: 20–JUL–2005<br />

5. Toxicity Substance ID: 71–43–2<br />

______________________________________________________________________________<br />

methods, the authors demonstrated increased recruitment of<br />

cells responsive to rGM–CSF following exposure to a variety<br />

of agents with documented leukemogenic potential. These<br />

findings support the possibility that transient alterations<br />

in HPC differentiation may be an important factor in the<br />

early stages of development of leukemia secondary to<br />

chemical or drug exposure.<br />

Source: Deutsche Shell Chemie GmbH Eschborn<br />

06–JAN–1997 (566)<br />

Type: other: Hematotoxicity<br />

Remark: This research involved exposure of CBA/Ca male mice to<br />

benzene vapor in varying concentrations. Exposure to 300<br />

ppm 6 hrs/day, 5 days/week, for 16 weeks is highly<br />

leukemogenic. Exposure for the same time to 100 ppm is<br />

alsoleukemogenic. Concentrations from 25 ppm to 400 ppm 6<br />

hrs/day, 5 days/week, for 10 exposures produce an<br />

increasinglymphopenia. Exposure to 100 ppm for the same<br />

exposure timeproduces anemia, decrease in stem cell content<br />

of marrow, and marrow cellularity.<br />

Source: Deutsche Shell Chemie GmbH Eschborn<br />

06–JAN–1997 (258)<br />

Type: other: Hematotoxicity<br />

Remark: Effects of benzene inhalation on mouse pluripotent<br />

hemapoietic stem cells were evaluated. Male mice 8–12 wk<br />

old were exposed to 400 ppm benzene for 6 h/d, 5 d/wk, for<br />

up to 9 1/2 wk. At various time intervals exposed and<br />

control animals were killed, and cardiac blood was<br />

evaluatedfor changes in white blood cell (WBC) and red blood<br />

cell (RBC) content. In addition, femora and tibiae were<br />

evaluated for total marrow cellularity, stem cell content<br />

(as measured by the spleen colony technique), and the<br />

percent of stem cells in DNA synthesis (as determined by<br />

thetritiated thymidine cytocide technique). Exogenous<br />

spleen colonies grown from marrow of exposed animals were<br />

counted, identified, and scored by histological type.<br />

Exposure to benzene caused sigificant depressions of RBCs<br />

and WBCs throughout the exposure period, which continued for<br />

at least14 d after exposure. Bone marrow cellularity and<br />

stem cell content were also depressed in exposed animals<br />

throughout the study. Tritiated thymidine cytocide of<br />

spleen colony–forming cells was generally increased in<br />

exposed animals, perhaps indicating a compensatory response<br />

to the reduction of circulating cells. Spleen colonies of<br />

all types were depressed after exposure to benzene.<br />

Source: Deutsche Shell Chemie GmbH Eschborn<br />

06–JAN–1997 (259)<br />

<strong>Appendix</strong> D: Benzene SIDS <strong>Dossier</strong><br />

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