Appendix D - Dossier (PDF) - Tera

date: 20–JUL–2005
5. Toxicity Substance ID: 71–43–2
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not teratogenic.
Source: BP Chemicals Ltd LONDON
Test substance: Supplied by Reanal, Budapest; p.a. grade.
24–OCT–2000 (1110)
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/day); 40 rats/dose
Control Group: yes, concurrent no treatment
NOAEL Maternal Toxity: = 100 ppm
NOAEL Teratogenicity: = 100 ppm
Method: other
GLP: no data
Test substance: no data
Remark: Two control groups consisting of 40 females 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.
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
average number of implantation sites, number of resorptions,
resorption incidence and number of live foetuses were
similar in all groups. A small, statistically significant
decrease in the average male and female foetal body weight
and non–significant, slight decrease in mean foetal body
length was recorded at 0.33 mg/l. A slight, non–significant
increase in dilation of the renal pelvis and ureters was
seen in the lowest– and top–dose groups and a small,
non–significant decrease in the average number of sternebrae
and caudal vertebrae occurred at 0.33 mg/l. No
benzene–induced skeletal variants or soft tissue anomalies
were reported. The investigators concluded that benzene was
slightly foetotoxic as shown by reduced foetal weights and
lengths and a statistically non–significant delay in
ossification of extremities and sternebrae at 0.33 mg/l.
Source: BP Chemicals Ltd LONDON
Appendix D: Benzene SIDS Dossier
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