Appendix D - Dossier (PDF) - Tera

date: 20–JUL–2005
5. Toxicity Substance ID: 71–43–2
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frequency over the background. Survival in these cultures
exceeded 10% and benzene was, therefore, judged to be
mutagenic in the presence of activation.
A similar positive result was reported by Styles J.A. et al.
Prog. Mutation Res. 5, 587–596, 1985: In the presence of
S9, benzene produced an unequivocal positive result at the
Na+/K+ ATPase locus (selected by resistance to ouabain) and
a weak result at the thymidine kinase locus (no such effect
was found in the absence of S9 but this was thought to be
due to excessive toxicity of benzene).
Matthews, E.J. et al., Prog. Mutat. Res. 5, 639–650 (1985),
reported also increased mutation frequency to ouabain
resistance at the Na+/K+ ATPase locus.
Source: Deutsche Shell Chemie GmbH Eschborn
Test substance: Laboratory reagent grade; 99% pure.
06–JAN–1997 (850)
Type: Mouse lymphoma assay
System of testing: L5178Y mouse lymphoma cells
Concentration: 12.5–200 ug/ml
Metabolic activation: with and without
Result: positive
Method: other: in compliance with OECD Guide–line 476
Year: 1984
GLP: no data
Test substance: other TS
Remark: Reliability: 2 (valid with restriction)
Comparable to guideline study with acceptable restrictions
no data about mean value and deviation, 2 plates per dose,
no 2nd independent experiment
results: From the preliminary study, a dose range of
12.5–200 ug/ml was determined. The mutant frequency was
statistically significantly increased in the 6–thioguanine
test in the absence of S9. No increased mutations to ouabain
resistance were detected.
The method of Cole J. et al. Mutation Res. 41, 377–386,
1976 was followed. Benzene was dissolved in
dimethylsulphoxide and diluted to obtain the required
concentration. Cells were treated in the presence and
absence of S9 mix (derived from Aroclor–1254–induced rats)
for 2 hours. Survival was determined initially at the
various concentrations tested without S9. In the
mutagenicity assay, after treatment, the cells were cultured
for 48 hours, mixed with ouabain and incubated for 2 weeks
or cultured for 7 days, mixed with 6–thioguanine and
incubated for 2 weeks. Benzo(a)pyrene and
4–nitroquinoline–1–oxide were the positive control chemicals
for the assays conducted with and without S9 respectively.
Dimethylsulphoxide was the negative solvent control.
Source: Deutsche Shell Chemie GmbH Eschborn
Test substance: Laboratory reagent grade.
06–JAN–1997 (394)
Appendix D: Benzene SIDS Dossier
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