N-(4-acetylaminophenyl)-3-hydroxynaphthalene-2-carboxamide

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Naphtol AS-ONSAP of RCC 1014801 is not mutagenic (higher purity) whereas the Naphtol AS-ONSAP sample of Hoe 92.0838 is mutagenic. This can be assumed to be due to the higher impurity content of this sample. Therefore the pure(r) REACH substance Naphtol AS-ONSAP can be concluded to be not mutagenic.

Link to relevant study records

Reference

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:

2006

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: performed in accordance with OECD and GLP guidelines

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Qualifier:

according to guideline

Guideline:

OECD Guideline 472 (Genetic Toxicology: Escherichia coli, Reverse Mutation Assay)

GLP compliance:

yes (incl. QA statement)

Type of assay:

bacterial reverse mutation assay

Species / strain / cell type:

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

Species / strain / cell type:

E. coli WP2 uvr A

Metabolic activation:

with and without

Metabolic activation system:

rat liver S9-mix

Test concentrations with justification for top dose:

1st experiment: 3 - 5000 µg/plate
2nd experiment: 3 - 5000 µg/plate

Vehicle / solvent:

Tested substance dissolved in DMSO

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: sodium azide (TA100, TA1535), 4-nitro-o-phenylene-diamine=4-NOPD (TA1537, TA98), methyl methane sulfonate=MMS (WP2uvrA)

Remarks:

without metabolic activation

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 2-aminoanthracene (all strains)

Remarks:

with metabolic activation

Details on test system and experimental conditions:

Method of application:
1st experiment: as plate incorporation assay
duration of incubation: at least 48h at 37°C in the dark

2nd experiment: as pre-incubation assay
duration of pre-incubation: 1h at 37°C
duration of incubation: at least 48h at 37°C in the dark

Determination of cytotoxicity:
Method: reduction of spontaneous revertants or clearing of the bactarial background lawn

Evaluation criteria:

Increase of revertant colonies

Statistics:

Number of colonies per plate for each strain as well as mean values of the colonies of 3 plates/dose were counted, corrected to the next higher integer.

Species / strain:

S. typhimurium TA 1535, TA 1537, TA 98 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

Species / strain:

E. coli WP2 uvr A

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

Additional information on results:

Visible precipitation of the test compound was observed in the 1st experiment at 333 µg/plate and above, in the 2nd experiment at 1000 µg/plate and above respectively

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Conclusions:

Interpretation of results (migrated information):
negative without metabolic activation
negative with metabolic activation

The test substance was not mutagenic in the presence and absence of a metabolizing system in this tested Salmonella typhimurium and Escherichia coli reverse mutation assay.

Executive summary:

Naphtol AS-ONSAP was tested for mutagenicity with the strains TA 100, TA1535, TA 1537, TA 98 of Salmonella typhimurium and Escherichia coli WP2uvrA.

The mutagenicity studies were conducted in the absence and in the presence of a metabolizing system derived from rat liver homogenate. A dose range of 8 different doses from 3 µg/plate to 5 000 µg/plate was used.

Toxicity: The test compound was proved to be not toxic to the bacterial strains.

Mutagenicity: In the absence of the metabolic activation system the test compound did not show a dose dependent increase in the number of revertants in any of the bacterial strains. Also in the presence of a metabolic activation system, treatment of the cells with Naphtol AS-ONSAP did not result in relevant increases in the number of revertant colonies.

It can be stated that Naphtol AS-ONSAP is not mutagenic in these bacterial test systems neither with nor without exogenous metabolic activation at the dose levels investigated.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Additional information

Additional information from genetic toxicity in vitro:

Justification for selection of genetic toxicity endpoint
REACH substance with a lower impurity profile