Appendix D - Dossier (PDF) - Tera

date: 20–JUL–2005
5. Toxicity Substance ID: 71–43–2
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sulphate and hydroquinone sulphate, mainly contributed to
the higher rate of benzene metabolism.
Source: Deutsche Shell Chemie GmbH Eschborn ;German rapporteur
Flag: Risk Assessment
14–SEP–2000 (859)
Type: Metabolism
Remark: The effect of induction by phenobarbital (PB),
beta–naphthoflavone (BNF), and benzene on benzene
metabolismwas studied in hepatic microsomes from male
Sprague–Dawley rats. Two distinct froms of mixed–function
oxidase activityappeared to metabolize benzene. One form
was active at all substrate concentrations in microsomes
from control, benzene–treated, and BNF–treated animals, and
at benzene concentrations of 0.8 mM and below in microsomes
from PB–treated animals. It was saturated at benzene
concentrations above 0.4 mM, had a pH optimum of
approximately 6.6, and was stimulated by fluoride.
Pretreatment with benzene, but not BNF, increased benzene
metabolism in these preparations. Benzene metabolism in
microsomes from PB–induced rats was less active than in
controls at benzene concentrations below 0.8 mM, but
increased rapidly at higher benzene concentrations.
Furthercharacteristics of the PB–induced enzyme activity
were that saturation was not observed at benzene
concentrations as high as 4 mM, the pH optimum for benzene
metabolism in thesepreparations was 7.1, metabolism was not
stimulated by fluoride, and metabolism was inhibited by
metyrapone. Both phenol and an unidentified polar component
were formed from benzene in all microsomal preparations.
Source: Deutsche Shell Chemie GmbH Eschborn ;German rapporteur
Flag: Risk Assessment
14–SEP–2000 (903)
Type: Metabolism
Remark: The metabolis interactions of benzene and toluene
co–exposure were investigated in male Fischer rats.
Endosedrecirculated exposure system was used to obtain
inhalation uptake curves for individual chemicals as well as
for a mixture of the two compounds. Pharmacokinetic
parameters for benzene and toluene individually were
determined in previous experimental studies. These values
were incorporated into a physiologically based
pharmacokinetic model which simulated the inhalation uptake
process for bothchemicals simultaneously. An optimal fit to
the uptake curves for simultaneous exposure was obtained by
adjusting the metabolic interaction terms for each chemical.
Mutual suppression of metabolism was apparent. Toluene
more effectively inhibited benzene metabolism than the
reverse.
Source: Deutsche Shell Chemie GmbH Eschborn
06–JAN–1997 (911)
Appendix D: Benzene SIDS Dossier
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