Appendix D - Dossier (PDF) - Tera

date: 20–JUL–2005
5. Toxicity Substance ID: 71–43–2
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male Sprague–Dawley rats. Exposure followed by 2 d
postexposure incubation period. Resistance to 8–azaguanine
was used as the genetic marker.
results: No evidence of mutagenicity was seen when benzene
was tested up to a concentration of 13 mM in this strain in
the presence of metabolic activation systems. Similar
results were reported by Seixas, G.M. et al., Mutat. Res.
102, 201–212 (1982, Reliability: 2 (valid with restriction))
Source: Deutsche Shell Chemie GmbH Eschborn
Test substance: Supplied by Aldrich Chemical Co., Milwaukee, Wisconsin;
purity unspecified.
06–JAN–1997 (591)
Type: other: Ames test (preincubation assay)
System of testing: Salmonella typhimurium strains TA98, 100, 104, 1535
Concentration: 3–1000ppm (converts to 0.009– 3.26 mg/l)
Metabolic activation: with and without
Result: positive
Method: other
GLP: no data
Test substance: no data
Remark: Reliability: 2 (valid with restriction)
No standard test procedure, but in accordance with generally
accepted scientific standards and described in sufficient
detail
no positive control, TA1537 not tested; no data about
cytotoxicity, test substance, standard deviation
results: Benzene was found to be mutagenic in the presence
but not the absence of S9. Strain TA1535 was the most
responsive. A benzene concentration as low as 0.03 mg/l
caused a two–fold increase in the number of mutants above
the control. In this same strain, the metabolites
trans–benzene–1,2–dihydrodiol in the presence of S9 and
anti–benzene–diol–epoxide and syn–benzene–diol–epoxide in
the absence of S9 induced mutations. No other metabolite,
including catechol to which trans–benzene–1,2–dihydrodiol is
converted by cytosolic dihydrodiol dehydrogenase, gave a
positive result in strain TA1535. Mutagenic responses, some
of them weak, were noted in other strains treated with
1,2,3–trihydroxybenzene, 1,2,4–trihydroxybenzene, catechol,
quinone, hydroquinone, syn–benzene–diol–epoxide and
anti–benzene–diol–epoxide.
Tests were conducted on benzene and its following
metabolites: benzene oxide, phenol, hydroquinone,
4,4’–dihydroxybiphenyl, 2,2’–dihydroxy–biphenyl, quinone,
trans–benzene–1,2–dihydrodiol, catechol and
1,2,4–tri–hydroxybenzene. Duroquinone,
anti–benzene–diol–epoxide, syn–benzene–diol–epoxide and
1,2,3–trihydroxybenzene were also included. S. typhimurium
was exposed to benzene vapour in desiccators to allow for
longer exposure periods. S9 mix derived from rat and mouse
liver homogenate was used as the activation system.
Metabolites also tested with strains TA97 and 102.
Source: Deutsche Shell Chemie GmbH Eschborn
06–JAN–1997 (416)
Appendix D: Benzene SIDS Dossier
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