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Genetic toxicity in vitro

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Endpoint:
in vitro gene mutation study in bacteria
Remarks:
Type of genotoxicity: gene mutation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1988
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP guideline study with full documentation
Justification for type of information:
Read-across from supporting substance (structural analogue or surrogate)
Qualifier:
according to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
yes
Remarks:
no positive controls were used for TA100, TA1535 and TA1537 with metabolic activation. However the number of revertants is very low. Also the number of cells per culture was not specified.
GLP compliance:
yes (incl. certificate)
Type of assay:
bacterial reverse mutation assay
Target gene:
Histidine independent mutant colonies of Salmonella typhimurium
Species / strain / cell type:
other: S. typhimurium TA 1535, TA 1537, TA 1538, TA 98 and TA 100
Additional strain / cell type characteristics:
other: histidine deficient
Metabolic activation:
with and without
Metabolic activation system:
Aroclor 1254 rat liver S9-mix
Test concentrations with justification for top dose:
10, 100, 500, 1000 and 5000 micrograms/plate
Untreated negative controls:
yes
Negative solvent / vehicle controls:
no
True negative controls:
not specified
Positive controls:
yes
Positive control substance:
other: sodium azide (without S9 for TA1535 and TA100; 9-aminoacridine without S9 for TA1537; 2-nitrofluorene without S9 for TA1538 and TA98; and 2-aminofluorene with S9 for TA1538 and TA98.
Remarks:
no positive controls were used used for TA100, TA1535 and TA1537 with metabolic activatiion; however the number of revertants is very low
Species / strain:
other: S. typhimurium TA 1535, TA 1537, TA 1538, TA 98 and TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
not applicable
Untreated negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Precipitation concentration was >5000 micrograms per plate

Conclusions:
Interpretation of results (migrated information):
negative

The test substance is not mutagenic in the AMES Test
Endpoint:
in vitro gene mutation study in bacteria
Remarks:
Type of genotoxicity: gene mutation
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1988
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Secondary source with limited details
Principles of method if other than guideline:
Six test substance concentrations; with and without metabolic activation; positive and negative controls; 3 replicates; application using preincubation assay with a 20 minute timeframe.
GLP compliance:
not specified
Type of assay:
bacterial reverse mutation assay
Target gene:
Histidine independent mutant colonies of Salmonella typhimurium
Species / strain / cell type:
other: TA97, TA98, TA100, TA1535
Additional strain / cell type characteristics:
other: histidine deficient
Metabolic activation:
with and without
Metabolic activation system:
liver S9 fraction (Aroclor 1254-induced) from rats (10 and 30%) and hamsters (10 and 30%)
Test concentrations with justification for top dose:
100, 333, 1000, 3333, 6667 (without activation) and 10000 (with activation) micrograms per plate
Untreated negative controls:
yes
Negative solvent / vehicle controls:
no
True negative controls:
yes
Positive controls:
yes
Positive control substance:
other: 2-aminoanthracene; 4-nitro-o-phenylenediamine; sodium azide, 9-aminoacridine
Remarks:
true negative control was DMSO
Species / strain:
other: TA97, TA98, TA100, TA 1535
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity, but tested up to precipitating concentrations
Vehicle controls validity:
not applicable
Untreated negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Precipitation concentration 10,000 micrograms per liter

Conclusions:
Interpretation of results (migrated information):
negative

Test substance is not mutagenic or cytotoxic in the Ames test
Endpoint:
in vitro cytogenicity / chromosome aberration study in mammalian cells
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
experimental study
Adequacy of study:
key study
Study period:
October 10-12, 1988
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP guideline study with full documentation
Justification for type of information:
Read-across from supporting substance (structural analogue or surrogate)
Qualifier:
according to
Guideline:
OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Type of assay:
in vitro mammalian chromosome aberration test
Species / strain / cell type:
Chinese hamster lung fibroblasts (V79)
Metabolic activation:
with and without
Metabolic activation system:
rat liver S9 fraction following Aroclor 1254 exposure
Test concentrations with justification for top dose:
200, 600, 1902 micrograms per milliliter
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: Ethylmethanesulfonate without S9 and cyclophosphamide with S9
Remarks:
solvent was xylene
Species / strain:
Chinese hamster lung fibroblasts (V79)
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Mitotic Index: Concentration related plating efficiency was established in 1000 cells from each of two slides per test group. No influence on mitotic index was observed.

The precipitation concentration was > 1902 ug/mL

Conclusions:
Interpretation of results (migrated information):
negative

The test substance does not induce chromosome mutations (aberrations) in V79 Chinese Hamster cells. The substance is neither mutagenic nor cytotoxic under the conditions of the study.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

There is a fully documented, GLP Guideline (OECD 471) Ames Test (Hoechst, 1988a) and a fully documented, GLP Guideline (OECD 473) Chromosome Aberration Test (Hoechst, 1988b) for one of the aromatic sulphonic acids, p-toluenesulphonic acid (CAS No. 104-15-4). Both tests were conducted with and without metabolic activation. The Ames test exposed up to 5000 micrograms/plate and the chromosome aberration test exposed up to 1902 micrograms per liter of the test substance. These studies conclude the substance is neither mutagenic norcytotoxic.

There is an additional, published report (Zeiger, 1988) of an Ames Test for another of the aromatic sulphonic acids, benzenesulphonic acid (CAS No. 98-11-3). Exposures up to 10,000 micrograms/plate were done with and without metabolic activation. The conclusion is the same as for the p-toluenesulphonic acid; that is, not mutagenic and notcytotoxic.

There are no in vivo mutagenicity studies for the aromatic sulphonic acids, but there are two in vivo mouse micronucleusstudies for the related hydrotropes – sodium cumene sulphonate (CAS 28348-53-0) (Sasol, 1992) and calcium xylene sulphonate (CAS 28088-63-3) (Ruetgers-Nease, 1994). Both are GLP-compliant Guideline mouse micronucleus studies with full documentation.  The Sasol study was an oral dose of 4467 mg/kg bw and the Ruetgers-Nease study was an IP injection exposure of up to 580 mg/kg bw. Both studies conclude the test substances were not mutagenic in these assays.

Short description of key information:

Negative

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

All study results are negative.

No classification for mutagenicity is warranted under 67/548/EEC or Regulation 1272/2008.