Disodium [N-[7-hydroxy-8-[(2-hydroxy-5-mesylphenyl)azo]-1-naphthyl]acetamidato(2-)][2-hydroxy-3-[(2-hydroxy-1-naphthyl)azo]-5-nitrobenzenesulphonato(3-)]chromate(2-)

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1983

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with national standard methods with acceptable restrictions

Justification for type of information:

Justification for read across is detailed in the report attached to the IUCLID section 13.

Cross-reference

Reason / purpose for cross-reference:

read-across source

Reference

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

1983

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with national standard methods with acceptable restrictions

Justification for type of information:

Justification for read across is detailed in the report attached to the IUCLID section 13.

Reason / purpose for cross-reference:

read-across source

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Remarks:

only four tester strains tested; no tester strain to detect cross-linking mutagens was included

Principles of method if other than guideline:

None

GLP compliance:

no

Type of assay:

bacterial reverse mutation assay

Specific details on test material used for the study:

None

Target gene:

Histidine for Salmonella

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Details on mammalian cell type (if applicable):

Strain Type of MutationS. typhimurium TA 100 base-pair substitutionS. typhimurium TA 1535 base-pair substitutionS. typhimurium TA 98 frame-shiftS. typhimurium TA 1537 frame-shift

Additional strain / cell type characteristics:

not applicable

Metabolic activation:

with and without

Metabolic activation system:

Rat-liver post mitochondrial supernatant (S9 fraction)

Test concentrations with justification for top dose:

0.2 to 2000 µg

Vehicle / solvent:

bidistilled water

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: Without S9: strains TA 1535 and TA 100 - MNNG, for Strain TA 98 - Daunomycine and for strain TA 1537 - 9-aminoacridine; with S9: 2-anthramine was used for all the strains

Details on test system and experimental conditions:

INDUCTION OF RAT LIVER ENZYMESThree male Sprague-Dawley rats weighing approximately 200 grams were given an i.p. injection of Aroclor 1254 (Monsanto) in peanut oil at a dose of 500 mg/kg.Five days after the injection, the rats were anaesthetized with ether, decapitated and the livers removed in a sterile manner. The livers were homogenizedin twice their volume of sterile 0.15 M KCl, pooled together and centrifuged for 15 min at 9000 xg (Beekman refrigerated ultracentrifuge). The supernatant(termed the S-9 fraction) was aliquoted into sterile tubes and frozen at -70°C.TEST SUBSTANCE AND CONCENTRATIONSA sample of the product FAT 20013/B (a brown dyestuff) was tested in S. typhimurium strains TA 1535, TA 1537, TA 98 and TA 100 at five dose levels: 0.2, 2, 20, 200 and 2000 (jg (or nl) per Petri dish. The test substance was dissolved in distilled water and every concentration was tested in triplicate.

Rationale for test conditions:

None

Evaluation criteria:

The criteria of mutagenicity used in this test are a doubling of the spontaneous reversion rate and a dose-effect relationship.

Statistics:

None

Key result

Species / strain:

other: For strains TA 1535, TA 1537 and TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Key result

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

positive

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Additional information on results:

None

None

Conclusions:

It is concluded that the metabolites exerted a mutagenic action on strain S. typhimurium TA 98.

Executive summary:

The study was performed to investigate the potential of Fteh Similar substance 01 to induce gene mutations according to the plate incorporation test using the Salmonella typhimurium strains TA 1535, TA 1537, TA 98 and TA 100. The assay was performed in two independent experiments both with and without liver microsomal activation.

Under the experimental conditions defined in the protocol, and employing a doubling of the spontaneous reversion rate and dose-effect relationship as criteria of mutagenicity, the product was found mutagenic for S. typhimurium strain TA 98. No mutagenic effect was observed with the strains TA 1535, TA 1537 and TA 100. With TA 98, the evidence of mutagenicity existed at 2000 µg in the presence of S-9 mix, and at 200 µg and 2000 µg of product per Petri dish without S-9 mix. In the absence of S-9 mix, at 2000 µg of product per plate, a toxic effect was noted with a dispersed background lawn. A complete disappearance of the background lawn was observed with the strains TA 1535 and TA 1537 at 2000 µg in the absence of S-9 mix.

It is concluded that the metabolites of the substance exerted a mutagenic action on strain S. typhimurium TA 98.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1983

Report date:

1983

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 tested; no tester strain to detect cross-linking mutagens was included

Principles of method if other than guideline:

None

GLP compliance:

no

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Similar substance 01 of Acid Black 213

IUPAC Name:

Similar substance 01 of Acid Black 213

Test material form:

solid: particulate/powder

Specific details on test material used for the study:

None

Method

Target gene:

Histidine for Salmonella

Species / strain

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Details on mammalian cell type (if applicable):

Strain Type of MutationS. typhimurium TA 100 base-pair substitutionS. typhimurium TA 1535 base-pair substitutionS. typhimurium TA 98 frame-shiftS. typhimurium TA 1537 frame-shift

Additional strain / cell type characteristics:

not applicable

Metabolic activation:

with and without

Metabolic activation system:

Rat-liver post mitochondrial supernatant (S9 fraction)

Test concentrations with justification for top dose:

0.2 to 2000 µg

Vehicle / solvent:

bidistilled water

Controls

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: Without S9: strains TA 1535 and TA 100 - MNNG, for Strain TA 98 - Daunomycine and for strain TA 1537 - 9-aminoacridine; with S9: 2-anthramine was used for all the strains

Details on test system and experimental conditions:

INDUCTION OF RAT LIVER ENZYMESThree male Sprague-Dawley rats weighing approximately 200 grams were given an i.p. injection of Aroclor 1254 (Monsanto) in peanut oil at a dose of 500 mg/kg.Five days after the injection, the rats were anaesthetized with ether, decapitated and the livers removed in a sterile manner. The livers were homogenizedin twice their volume of sterile 0.15 M KCl, pooled together and centrifuged for 15 min at 9000 xg (Beekman refrigerated ultracentrifuge). The supernatant(termed the S-9 fraction) was aliquoted into sterile tubes and frozen at -70°C.TEST SUBSTANCE AND CONCENTRATIONSA sample of the product FAT 20013/B (a brown dyestuff) was tested in S. typhimurium strains TA 1535, TA 1537, TA 98 and TA 100 at five dose levels: 0.2, 2, 20, 200 and 2000 (jg (or nl) per Petri dish. The test substance was dissolved in distilled water and every concentration was tested in triplicate.

Rationale for test conditions:

None

Evaluation criteria:

The criteria of mutagenicity used in this test are a doubling of the spontaneous reversion rate and a dose-effect relationship.

Statistics:

None

Results and discussion

Test results

Test results 1

Key result

Species / strain:

other: For strains TA 1535, TA 1537 and TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Test results 2

Key result

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

positive

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Additional information on results:

None

Any other information on results incl. tables

None

Applicant's summary and conclusion

Conclusions:

It is concluded that the metabolites exerted a mutagenic action on strain S. typhimurium TA 98.

Executive summary:

The study was performed to investigate the potential of Fteh Similar substance 01 to induce gene mutations according to the plate incorporation test using the Salmonella typhimurium strains TA 1535, TA 1537, TA 98 and TA 100. The assay was performed in two independent experiments both with and without liver microsomal activation.

Under the experimental conditions defined in the protocol, and employing a doubling of the spontaneous reversion rate and dose-effect relationship as criteria of mutagenicity, the product was found mutagenic for S. typhimurium strain TA 98. No mutagenic effect was observed with the strains TA 1535, TA 1537 and TA 100. With TA 98, the evidence of mutagenicity existed at 2000 µg in the presence of S-9 mix, and at 200 µg and 2000 µg of product per Petri dish without S-9 mix. In the absence of S-9 mix, at 2000 µg of product per plate, a toxic effect was noted with a dispersed background lawn. A complete disappearance of the background lawn was observed with the strains TA 1535 and TA 1537 at 2000 µg in the absence of S-9 mix.

It is concluded that the metabolites of the substance exerted a mutagenic action on strain S. typhimurium TA 98.