Appendix D - Dossier (PDF) - Tera

date: 20–JUL–2005
5. Toxicity Substance ID: 71–43–2
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reduction in absolute and relative thymus weight and spleen
B– and T–lymphocytes. There was no effect on the bone marrow
cellularity at any time or treatment group.
In male Sprague–Dawley rats, no significant effect on the
humoral immune response was measured in an ELISA of serum
anit–SRBC IgM. SRBC was injected four days prior to the
completion of 2 or 4–week exposure to 30, 200, or 400 ppm
benzene vapour (6 hr/d, 5 d/w).
Source: German Rapporteur
Flag: Risk Assessment
06–JUL–2005 (952)
Species: rat Sex: male/female
Strain: Sprague–Dawley
Route of administration: inhalation
Exposure period: 13 weeks
Frequency of treatment: 6 hours per day/5 days per week
Post exposure period: none
Doses: 1, 10, 30, 300 ppm (converts to 0.003, 0.033, 0.098,
0.98 mg/l); 50 rats/sex/dose
Control Group: yes, concurrent no treatment
NOAEL: = 10 ppm
LOAEL: = 30 ppm
Method: Directive 87/302/EEC, part B, p. 20 "Sub–chronic inhalation
toxicity study: 90–day repeated dose study using rodent
species"
GLP: no data
Method: 50 rats/sex/group were exposed to benzene vapour (whole body
exposure) at concentrations of 3.2, 32, 96 or 960 mg/m³ (1,
10, 30 or 300 ppm) for 6 hr/day, 5 days/week for up to 13
weeks, and 10 rats/sex/group sacrificed after 7, 14, 28, 56,
and 91 days of treatment.
All animals were examined twice daily for mortality and
moribundity throughout the study. Observations for signs of
toxicity were made weekly. On days 7, 14, 28, 56 and 91,
blood samples were obtained at necropsy from ten randomly
selected rats/sex/group. Complete necropsies were performed
on all of these sacrificed animals and on all animals found
dead or moribund.
Result: No exposure–related mortality, clinical observations or mean
body weight changes were seen. In the high–dosed animals, a
significant decrease in the white blood cell count and, from
day 14, the percentage of lymphocytes was noted. No
exposure–related gross pathologic observations were
reported. Females exposed to 0.098 mg/l had significantly
increased mean thyroid weights and, on histopathological
examination of the high–dosed animals, lower femoral bone
marrow cellularity was noted on days 7, 28, 56 and 91. No
data on morphology or cellularity are reported for the
lower dosed animals.
Source: BP Chemicals Ltd LONDON
Deutsche Shell Chemie GmbH Eschborn
German Rapporteur
Appendix D: Benzene SIDS Dossier
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