2,2'-[(3,3'-dimethyl[1,1'-biphenyl]-4,4'-diyl)bis(azo)]bis[4-nonylphenol]

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Gene mutation in vitro:

Ames test:

The test chemical 2,2'-[(3,3'-dimethyl [1,1'-biphenyl]-4,4'-diyl)bis (azo)] bis[4-nonylphenol] (CAS no 67990 -27 -6) is not mutagenic to the Salmonella typhimurium strains in the presence and absence of liver S9 metabolic activation system and hence it is not likely to classify as a gene mutant in vitro.

Link to relevant study records

Reference

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

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

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Remarks:

experimental data of read across substances

Justification for type of information:

Data for the target chemical is summarized based on the structurally similar read across chemicals

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Principles of method if other than guideline:

WoE derived based on the experimental data from structurally and functionally similar read across chemicals

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Target gene:

Histidine

Species / strain / cell type:

S. typhimurium, other: TA98 and TA100

Remarks:

1

Details on mammalian cell type (if applicable):

No data

Additional strain / cell type characteristics:

not specified

Species / strain / cell type:

S. typhimurium, other: TA100, TA98, TA1535, TA1537 and TA1538

Details on mammalian cell type (if applicable):

Not applicable

Additional strain / cell type characteristics:

not specified

Cytokinesis block (if used):

No data

Metabolic activation:

with and without

Metabolic activation system:

Liver S9 was prepared from Aroclor-induced male Fischer F344 rats

Test concentrations with justification for top dose:

1. 0, 222, 444, 888, 1776 or 3552 µg/plate
2. 200 µg/Plate

Vehicle / solvent:

1./2. - Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: The test chemical is soluble in DMSO

Untreated negative controls:

not specified

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

other: 2-aminoanthracene

Remarks:

1

Untreated negative controls:

not specified

Negative solvent / vehicle controls:

not specified

True negative controls:

yes

Positive controls:

yes

Positive control substance:

4-nitroquinoline-N-oxide

ethylmethanesulphonate

methylmethanesulfonate

other: Anthragallol, 2-Anthramine

Details on test system and experimental conditions:

1. METHOD OF APPLICATION: Liquid preincubation

DURATION
- Preincubation period: 30 mins in gyratory water bath
- Exposure duration: No data
- Expression time (cells in growth medium): No data
- Selection time (if incubation with a selection agent): No data available
- Fixation time (start of exposure up to fixation or harvest of cells): No data available

SELECTION AGENT (mutation assays): No data available
SPINDLE INHIBITOR (cytogenetic assays): No data available
STAIN (for cytogenetic assays): No data available

NUMBER OF REPLICATIONS: Triplicate

NUMBER OF CELLS EVALUATED: No data available

DETERMINATION OF CYTOTOXICITY
- Method: mitotic index; cloning efficiency; relative total growth; other: No data available

OTHER EXAMINATIONS:
- Determination of polyploidy: No data available
- Determination of endoreplication: No data available
- Other: No data available

OTHER: No data available

2. METHOD OF APPLICATION: Spot test

DURATION
- Preincubation period: No data
- Exposure duration: 72 hrs
- Expression time (cells in growth medium): 72 hrs
- Selection time (if incubation with a selection agent): No data
- Fixation time (start of exposure up to fixation or harvest of cells): No data

SELECTION AGENT (mutation assays): No data
SPINDLE INHIBITOR (cytogenetic assays): No data
STAIN (for cytogenetic assays): No data

NUMBER OF REPLICATIONS: No data

NUMBER OF CELLS EVALUATED: No data

DETERMINATION OF CYTOTOXICITY
- Method: mitotic index; cloning efficiency; relative total growth; other: No data

OTHER EXAMINATIONS:
- Determination of polyploidy: No data
- Determination of endoreplication: No data
- Other: No data

OTHER: No data

Rationale for test conditions:

No data

Evaluation criteria:

1. The plates were observed for increase in the number of revertants/plate
2. The criteria adopted for scoring a mutagenic response in routine plate tests was that the observed number of revertants should exceed twice the background value for that given assay and exceed the 99.9% confidence limit based on our historical controls.

Statistics:

1. Mean ± SD
2. No data

Species / strain:

S. typhimurium, other: TA98 and TA100

Remarks:

1

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

valid

Untreated negative controls validity:

not specified

Positive controls validity:

valid

Species / strain:

S. typhimurium, other: TA100, TA98, TA1535, TA1537 and TA1538

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

not specified

Untreated negative controls validity:

not specified

Positive controls validity:

valid

Additional information on results:

1/2.. No data

Remarks on result:

other: No mutagenic potential

Conclusions:

The test chemical 2,2'-[(3,3'-dimethyl[1,1'-biphenyl]-4,4'-diyl)bis(azo)]bis[4-nonylphenol] is not mutagenic to the Salmonella typhimurium strains in the presence and absence of liver S9 metabolic activation system and hence it is not likely to classify as a gene mutant in vitro.

Executive summary:

Data available for the test chemical was reviewed to determine its mutagenic nature of 2,2'-[(3,3'-dimethyl [1,1'-biphenyl]-4,4'-diyl)bis (azo)] bis[4-nonylphenol]. The studies are as mentioned below:

The test chemical was studied for its ability to induce mutations in strains of Salmonella typhimurium TA98 and TA100. The test compound was dissolved in DMSO and was tested at concentration of 0, 222, 444, 888, 1776 or 3552 µg/plate using Salmonella typhimurium TA100 and TA98 in the presence and absence of liver S9 metabolic activation system. Liquid preincubation assay was performed with a preicubation for 30 mins. The plates were observed for histidine independence. Concurrent solvent and positive controls were included in the study. The test chemical is not mutagenic to the Salmonella typhimurium TA100 and TA98 in the presence and absence of liver S9 metabolic activation system and hence it is not likely to classify as a gene mutant in vitro.

In another study, Gene mutation by the spot assay was performed for the test chemical. The given chemical was used at dose level of 200 µg/plate both with and without S9 metabolic activation system. The plates were incubated for 3 days at 37°C for the growth of colonies to occur. The plates were observed for an increase in the number of His+ revertants. The criteria adopted for scoring a mutagenic response in routine plate tests was that the observed number of revertants should exceed twice the background value for that given assay and exceed the 99.9% confidence limit based on our historical controls. Concurrent positive control was also included in the study. The test chemical did not induce mutation in Salmonella typhimurium strain TA100, TA98, TA1535, TA1537 and TA1538 with and without S9 metabolic activation system in the spot test performed and hence is not likely to classify for gene mutation in vitro.

Based on the data available for the test chemical, 2,2'-[(3,3'-dimethyl[1,1'-biphenyl]-4,4'-diyl)bis(azo)]bis[4-nonylphenol] is not mutagenic to the Salmonella typhimurium strains in the presence and absence of liver S9 metabolic activation system and hence it is not likely to classify as a gene mutant in vitro.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Gene mutation in vitro:

Data available for the test chemical was reviewed to determine its mutagenic nature of 2,2'-[(3,3'-dimethyl [1,1'-biphenyl]-4,4'-diyl)bis (azo)] bis[4-nonylphenol] (CAS no 67990 -27 -6). The studies are as mentioned below:

The test chemical was studied for its ability to induce mutations in strains of Salmonella typhimurium TA98 and TA100. The test compound was dissolved in DMSO and was tested at concentration of 0, 222, 444, 888, 1776 or 3552 µg/plate using Salmonella typhimurium TA100 and TA98 in the presence and absence of liver S9 metabolic activation system. Liquid preincubation assay was performed with a preicubation for 30 mins. The plates were observed for histidine independence. Concurrent solvent and positive controls were included in the study. The test chemical is not mutagenic to the Salmonella typhimurium TA100 and TA98 in the presence and absence of liver S9 metabolic activation system and hence it is not likely to classify as a gene mutant in vitro.

In another study, Gene mutation by the spot assay was performed for the test chemical. The given chemical was used at dose level of 200 µg/plate both with and without S9 metabolic activation system. The plates were incubated for 3 days at 37°C for the growth of colonies to occur. The plates were observed for an increase in the number of His+ revertants. The criteria adopted for scoring a mutagenic response in routine plate tests was that the observed number of revertants should exceed twice the background value for that given assay and exceed the 99.9% confidence limit based on our historical controls. Concurrent positive control was also included in the study. The test chemical did not induce mutation in Salmonella typhimurium strain TA100, TA98, TA1535, TA1537 and TA1538 with and without S9 metabolic activation system in the spot test performed and hence is not likely to classify for gene mutation in vitro.

Based on the data avalable for the test chemical, 2,2'-[(3,3'-dimethyl[1,1'-biphenyl]-4,4'-diyl)bis(azo)]bis[4-nonylphenol] (CAS no 67990 -27 -6) does not exhibit gene mutation in vitro. Hence the test chemical is not likely to be mutagenic as per the criteria mentioned in CLP regulation.

Justification for classification or non-classification

Based on the data avalable for the test chemical, 2,2'-[(3,3'-dimethyl[1,1'-biphenyl]-4,4'-diyl)bis(azo)]bis[4-nonylphenol] (CAS no 67990 -27 -6) does not exhibit gene mutation in vitro. Hence the test chemical is not likely to be mutagenic as per the criteria mentioned in CLP regulation.