Appendix D - Dossier (PDF) - Tera

date: 20–JUL–2005
5. Toxicity Substance ID: 71–43–2
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06–JAN–1997 (1245)
Type: Metabolism
Remark: Bone marrow stromal cells from mice were significantly more
susceptible to the cytotoxicity induced by the benzene
metabolites hydroquinone (HQ) and benzoquinone (BQ) than
cells from rats. Since cellular glutathione (GSH) and
quinone reductase (QR) are known to play critical roles in
modulating HQ–induced cytotoxicity, the GSH content and the
QR and glutathione S–transferase (GST) activity in stromal
cells from both species was measured. In rat cells, the
GSHcontent and the QR specific activity were 2 and 28 times
as much as those from mice, respectively. GSH and QR in
both mouse and rat stromal cells were inducible by
1,2–dithiole–3–thione (D3T). D3T pretreatment of both
mouseand rat stromal cells resulted in a marked protection
against HQ–induced toxicity. Pretreatment of both mouse
andrat stromal cells with GSH ethyl ester also provided a
dramatic protection against HQ–induced toxicity.
Conversely, dicoumarol, an inhibitor of QR, enhanced the
HQ–induced toxicity in stromal cells from both mice and
rats, indicating an important role for QR in modulating
HQ–induced stromal toxicity in both species.
Source: Deutsche Shell Chemie GmbH Eschborn ;German rapporteur
Flag: Risk Assessment
14–SEP–2000 (1311)
Type: Neurotoxicity
Remark: methods: narcotic properties of benzene studied on 10
rabbits exposed to 3.5–4.5% benzene vapor in air.
results:
symptoms average time of occurrence in minutes
light anesthesia, relaxed 3.7
excitation (running movement, tremor, chewing) 5.0
pupillary reflex lost 6.5
loss of blink reflex to tactual stimulus 11.4
pupillary contraction 12.0
involuntary blinking 15.6
death 36.2
Source: Deutsche Shell Chemie GmbH Eschborn
Test substance: no data
06–JAN–1997 (177)
Type: Neurotoxicity
Remark: method: 5 male CD–1 mice per group were fed drinking water
containing 0, 31, 166, or 790 mg/l benzene (analytical) for
28 d; at termination monoamine neurotransmitter
concentrations in different brain regions were determined.
results: no significant effects on body weight gain, water
and food consumption; benzene doses correspond to 0, 8, 40,
180 mg/kg/d, respectively; dose dependent significant
increase in norepinephrine (hypothalamus, medulla oblongata,
Appendix D: Benzene SIDS Dossier
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