Appendix D - Dossier (PDF) - Tera

date: 20–JUL–2005
5. Toxicity Substance ID: 71–43–2
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5.7 Carcinogenicity
Species: mouse Sex: male
Strain: C57BL
Route of administration: inhalation
Exposure period: life–time
Frequency of treatment: 6 hours per day/5 days per week
Post exposure period: none
Doses: 300 ppm (converts to 0.98 mg/l); 40 mice
Control Group: yes, concurrent vehicle
Method: other
GLP: no data
Test substance: no data
Remark: C57Bl/6J strain mice were used. Control group consisted of
40 males exposed to filtered, conditioned air under the same
exposure regime as above. Benzene concentrations in the
exposure chambers were determined every ½–hour during the
daily exposures. Animals were observed daily for evidence
of morbidity and weighed weekly for the first 4 weeks and
biweekly thereafter. Blood was withdrawn from ten test and
ten control mice every other week throughout the study. The
lung, liver, spleen, kidney, bone marrow and any abnormally
appearing organs were examined histologically. Exposure
ended after 488 days when the last test animal died.
Result: Median survival time and body weight gain were decreased in
treated mice. Haematological studies were suspended after
61 weeks as too few animals were alive in the test group.
Statistically significant increases in lymphocytopenia and
anaemia were seen throughout the study and neutrophilia was
evident after 17 weeks. Changes were observed in the
peripheral blood cell morphology of the treated animals
including anisocytosis (variation in red blood cell size),
poikilocytosis (variation in red blood cell shape), giant
platelets and, concurrent with neutrophilia, hyperlobulated,
mature neutrophils and neutrophilic left shift. On
histopathologic examination, the incidences of
haematopoietic neoplasms and bone marrow and splenic
hyperplasias (without evidence of haematopoietic neoplasm)
were statistically significantly increased when compared
with the control group (8/40, 13/32 and 10/32 in the treated
and 2/40, 0/38 and 2/38 in the control group for the three
tumours respectively). Six of the eight test animals
showing haematopoietic neoplasms had lymphocytic lymphoma
with thymic involvement, a significant increase when
compared with the two control animals showing lymphocytic
lymphoma without thymic involvement.
Source: BP Chemicals Ltd LONDON
Deutsche Shell Chemie GmbH Eschborn
German Rapporteur
Flag: Risk Assessment
01–JUL–2005 (1066)
Appendix D: Benzene SIDS Dossier
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