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Toxicological information

Genetic toxicity: in vitro

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Administrative data

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:
1992
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP compliant study conducted similar to OECD guideline 471 with only minor limitations.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1992
Report date:
1992

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
yes
Remarks:
only four tester strains investigated, limited purity of 77%
GLP compliance:
yes
Type of assay:
bacterial reverse mutation assay

Test material

Constituent 1
Chemical structure
Reference substance name:
Naphthalene-1,5-disulphonic acid
EC Number:
201-317-9
EC Name:
Naphthalene-1,5-disulphonic acid
Cas Number:
81-04-9
Molecular formula:
C10H8O6S2
IUPAC Name:
naphthalene-1,5-disulfonic acid
Test material form:
solid: crystalline
Details on test material:
- Name of test material (as cited in study report): 1,5-Naphtalenedisulfonic acid tetrahydrate
- Physical state: white crystalline powder
- Analytical purity: 77%
- Lot/batch No.: N0074
- Expiration date of the lot/batch: 15 July, 1992
- Storage condition of test material: refrigerator

Method

Target gene:
his operon
Species / strain
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Metabolic activation:
with and without
Metabolic activation system:
cofactor supplemented post-mitochondrial fraction (S9-mix), prepared from the livers of rats treated with Aroclor 1254.
Test concentrations with justification for top dose:
Experiment I:
- 8, 40, 200, 1000 and 5000 µg/plate (with and without metabolic activation)
Experiment II:
- 150, 300, 600, 1200, 2400 and 4800 µg/plate (with and without metabolic activation)
Controls
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: without S9-mix: sodium azide, 10 µg/plate (TA 1535); nitrofurantoin, 0.2 µg/plate (TA 100); 4-nitro-1,2-phenylene diamine, 10 µg/plate (TA 1537) and 0.5 µg/plate (TA 98); with S9-mix: 2-aminoanthracene, 3 µg/plate (TA 1535, TA 1537, TA 98 and TA 100)
Remarks:
DMSO was used as vehicle for the positive controls

Results and discussion

Test results
Species / strain:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Remarks:
No increase in revertant count was observed
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
A significant decrease in bacterial count (titre assessment) was observed ≥200 µg/plate (TA 1535, TA 100, TA 98) and ≥600 µg/plate (TA 1537)
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Applicant's summary and conclusion

Executive summary:

1,5-Naphthalenedisulfonic acid was investigated using the Salmonella/microsome test for point mutagenic effects in doses of up to 5000 µg per plate on four Salmonella typhimurium LT2 mutants. These comprised the histidine-auxotrophic strains TA 1535, TA 100, TA 1537 and TA 98.

Doses of up to and including 150 µg per plate did not cause any bacteriotoxic effects: Total bacteria counts remained unchanged and no inhibition of growth was observed. At higher doses, the substance had a strain-specific bacteriotoxic effect. However, this range could nevertheless be used for assessment purposes.

Evidence of mutagenic activity of 1,5-naphthalenedisulfonic acid was not seen. No biologically relevant increase in the mutant count, in comparison with the negative controls, was observed. Therefore, 1,5-naphthalenedisulfonic acid was considered tobe non-mutagenic without and with S9 mix in the Salmonella/microsome test.

The positive controls sodium azide, nitrofurantoin, 4-nitro- 1,2-phenylene diamine and 2-aminoanthracene had a marked mutagenic effect, as was seen by a biologically relevant in­ crease in mutant colonies compared to the corresponding negative controls.