Appendix D - Dossier (PDF) - Tera

date: 20–JUL–2005
5. Toxicity Substance ID: 71–43–2
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Source: Deutsche Shell Chemie GmbH Eschborn
06–JAN–1997 (410)
Type: other: Hematotoxicity
Remark: Inhaled benzene hematotoxicity to recognize stem cell
progeny was studied in male CD–1 mice exposed for 6 hr/day
x5 days to one of the following approximate benzene
concentrations: 1.0, 10, 100, 300, 600, 1280, 2400, and
4860ppm. Additional groups of mice were exposed for 6
hr/day x 5 days/week x 10 weeks to 9.6 ppm, or 6hr/day x 5
days/week x 26 weeks to 300 ppm. Following the 5–day
exposures, granulocytopenia and lymphocytopenia were
observed at levels>/= 100 ppm with no change in WBC
differential. RBC counts were depressed only at the two
highest exposure levels whilehematocrits were variably
affected and showed no clear dose/response effect. Marrow
and splenic cellularities werereduced at all levels >/= 100
ppm. Marrow lymphocytes, splenic lymphocytes, and marrow
granulocytes were reduced inaccordance with the reduction in
total cellularity, however,splenic granulocytes and spleen
weights were depressed at almost all exposure levels.
Nucleated RBCs in the marrow and spleen were depressed at
all levels >/= 100 ppm. Exposure for 50 days to 9.6 ppm
benzene, a total dose equivalent to that delivered over 5
days at 100 ppm, inducedno detectable changes in the
peripheral blood or bone marrow.
Source: Deutsche Shell Chemie GmbH Eschborn
06–JAN–1997 (439)
Type: other: Hematotoxicity
Remark: In order to investigate the interaction of inhaled benzene
with hematopoietic stem cells, marrow and spleen cells from
male CD–1 mice were assayed for CFU–S by the spleen colony
method, and for GM–CFU–C by an in vitro agar technique
following benzene exposure using a number of regimes.
Specifically, these consisted of a 6 hr/day x 5 days
exposure to either 1, 10, 100, 300, 600, 1280, 2400, or
4860ppm (Experiment 1); a 6 hr/day x 5 days/week x 50 days
exposure to 9.6 ppm (Experiment 2); and a 6 hr/day x 5
days/week x 26 weeks exposure to 300 ppm (Experiment 3).
InExperiment 1 femoral and splenic cellularites were
significantly reduced at concentrations >/= 100 ppm.
Marrowconcentrations of GM–CFU–C was equivalent to or
greater thancontrol values at all levels, however, splenic
GM–CFU–C concentration was decreased at 100 ppm and above.
Femoral and splenic CFU–S and GM–CFU–C per organ were
depressed at 100 ppm and above. Experiment 2 was designed
to compare theeffects of a 10–ppm exposure delivered over 50
days with the100–ppm exposure delivered over 5 days. In
Experiment 2, nodetectable changes were observed in bone
marrow, but spleniccellularity and the number and
concentration of splenic CFU–S were elevated vs matched
control. Experiment 3 repeated a regime that produced two
Appendix D: Benzene SIDS Dossier
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