Appendix D - Dossier (PDF) - Tera

date: 20–JUL–2005
5. Toxicity Substance ID: 71–43–2
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Test substance: >99.9% pure.
Flag: Risk Assessment
06–JUL–2005 (1237)
Species: rat Sex: male/female
Strain: Sprague–Dawley
Route of administration: inhalation
Exposure period: 6–31 wk
Frequency of treatment: 5 h/d, 4 d/wk
Doses: several dosing regimens (15–831 ppm)
Control Group: yes
LOAEL: 15 ppm
Method: other
Method: 5 hr/d, 4 d/w:
46 d/831 ppm
39 d/65 ppm
154 d/15 ppm
7 hr/d, 4 d/w:
245 d/47 ppm
54 d/44 ppm
126 d/31 ppm
88 d/29 ppm
Result: In an early less documented study of Deichmann et al. (1963)
groups of 40 Sprague–Dawley rats were exposed for 5 hr/d on
4 d/w for 6 to a maximum of 31 weeks to benzene vapour
(whole body exposure). Hematology was done at weekly or
biweekly intervals in 10 male and 10 female randomly picked
animals. Rats exposed to a mean concentration of 831 ppm on
32 days over a period of 46 days had reduced number of WBC
in males and females after one week of exposure and
thereafter. Another treatment with mean exposure to 65 ppm
on 26 days over a total period of 39 days showed reduced
number of WBC beginning at the treatment week 2 in females
and week 4 in males. Leucopenia became also apparent in rats
exposed to 47 ppm of benzene for 7 hr/d on 180 days over a
total of 245 days. A mean benzene vapour concentration of 44
ppm induced leucopenia gaining significance in males at week
7 and in females at week 5. Animals were sacrificed at week
8 after 45–54 periods of exposure. Concentrations of 31 ppm
on 126 days (7 hr/d, 4 d/w), 29 ppm on 88 days (7 hr/d, 4
d/w) or 15 ppm on 154 days (5 d/w) did not induce changes in
WBC counts. The spleen of rats of the 15 ppm, 31 ppm and 47
ppm groups examined microscopically revealed a higher
incidence and severity of hemosiderosis (females>males). The
authors summarized that the degree of leucopenia was similar
in rats exposed to 65 ppm or 831 ppm, but exposure to higher
concentration induced an earlier response. The leucopenia
was less severe in rats exposed to 44 and 47 ppm. Female
rats were more susceptible to leucopenia than males. The
NOAEL for effects on peripheral blood was 31 ppm. However,
no clear NOAEL for all adverse effects was established due
to increased incidence/severity of splenic hemosiderosis at
doses 15 ppm and above.
Source: German Rapporteur
Appendix D: Benzene SIDS Dossier
– 375/957 –