Appendix D - Dossier (PDF) - Tera

date: 20–JUL–2005
5. Toxicity Substance ID: 71–43–2
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sacral vertebrae at 0.45 mg/l[150 ppm]; one case of fused
metacarpal and carpal bones at 1.5 mg/l [500 ppm] and one
case of missing orbita). The incidence of these
malformations was not considered to have been increased and
the investigators concluded that benzene was not
teratogenic.
No maternal deaths were seen at 0.15 mg/l (50 ppm), however
1–3 animals/ group died in the other treatment groups after
completion of the exposures. Dissection revealed fresh
haemorrhages in the lungs and kidneys and multiple incipient
necroses in the liver, indicating ischaemia. Maternal
weight gain and placental weight were statistically
significantly decreased in all the treatment groups and
liver/body weight ratio significantly increased at 0.45 mg/l
(150 ppm) and above.
Source: German rapporteur; Deutsche Shell Chemie GmbH Eschborn
Test substance: Supplied by Reanal, Budapest; p.a. grade.
Flag: Risk Assessment
17–JUN–2005 (1111)
Species: rat Sex: female
Strain: Sprague–Dawley
Route of administration: inhalation
Exposure period: gestation days 6–15
Frequency of treatment: daily/6 hours per day
Duration of test: gestation day 20
Doses: 1, 10, 40, 100 ppm/day (converts to 0.003, 0.033,
0.12, 0.33 mg/l); 40 rats/dose used
Control Group: yes, concurrent vehicle
NOAEL Maternal Toxity: = 100 ppm
NOAEL Teratogenicity: = 100 ppm
Method: other
GLP: no data
Test substance: other TS: technical grade benzene, purchased from API
Remark: Two control groups consisting of 40 dams were exposed to
filtered room air. Animals were examined prior to, during
and after daily exposure and weighed at intervals. On day
20 dams were sacrificed and necropsied. Foetuses were
removed by caesarian section and weighed and measured.
Numbers of corpora lutea/ovary, implantation sites,
resorptions and live and dead foetuses were recorded for
each dam. Foetuses were examined for gross external
variations and either sectioned to examine for visceral
abnormalities or examined for skeletal abnormalities.
Benzene vapour concentrations were determined daily and the
mean ranges by infrared and gas chromatographic analyses
found to be 1.02, 8.36–11.02, 37.36–41.21 and 96.59–104.15
ppm (0.003, 0.028–0.036, 0.12–0.14 and 0.32–0.34 mg/l) for
the four groups respectively. Benzene chamber concentration
variability ranged from 3–13%.
Result: No deaths and no treatment–related clinical signs or gross
pathology were noted in the dams and the pregnancy rate was
within the expected range. Average maternal body weight
gain was very slightly lower than the controls in the
top–dose but this was not statistically significant. The
Appendix D: Benzene SIDS Dossier
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