Biphenyl-4,4'-diyl tetrakis(2,6-dimethylphenyl) bis(phosphate)

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

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:

15-22 May 2014

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Data have been generated according to current internationally recognised study guidelines and in accordance with GLP

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial 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, TA 100 and E. coli WP2

Metabolic activation:

with and without

Vehicle / solvent:

Dimethyl sulfoxide (DMSO):
Manufacturer: SIGMA-ALDRICH
Batch No.: SZBD1830V
Expiry date: 16 June 2016

Distilled water:
Manufacturer: TEVA Zrt.
Batch No.: 0790713
Expiry date: 31 July 2016

N,N-Dimethylformamide (DMF):
Manufacturer: SIGMA-ALDRICH
Batch No.: SZBD2210V
Expiry date: 24 July 2016

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

DMSO, Distilled Water, DMF

True negative controls:

no

Positive controls:

yes

Positive control substance:

9-aminoacridine

sodium azide

methylmethanesulfonate

other: 4-nitro-1,2-phenylene-diamine (NPD), 2-aminoanthracene (2AA)

Species / strain:

S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Positive controls validity:

valid

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

In the Range Finding Test the concentrations examined were: 2500, 1000, 316, 100, 31.6, 10 and 3.16 μg/plate.

The observed numbers of revertant colonies were in the normal range. Minor differences compared to the solvent control numbers were observed in some sporadic cases. However, they had no biological significance and were within the historical control range in all cases; thus, they were considered as reflecting the variability of the test system.

Slight precipitate was detected on the plates in all examined strains in the highest concentration with and without metabolic activation. There was no insolubility or signs of inhibitory, cytotoxic effect of the test item in the Preliminary Range Finding Test.

Examined concentrations in the main tests were 2500, 1250, 625, 312.5, 156.25, 78.125 and 39.063 test item/plate.

In the Initial Mutation Test and Confirmatory Mutation Test none of the observed revertant colony numbers were above the respective biological threshold value. There were no reproducible dose-related trends and no indication of any treatment effect.

Using the plate incorporation method (Initial Mutation Test), the highest revertant rate was observed in Salmonella typhimurium TA100 bacterial strain without metabolic activation at 312.5 μg/plate concentration. The mutation factor value was 1.20. The observed mutation factor values were below the biologically relevant threshold limit and the numbers of revertant colonies were within the historical control range.

Using the pre-incubation method (Confirmatory Mutation Test), the highest revertant rate was observed in Salmonella typhimurium TA1537 bacterial strain with metabolic activation at 39.063 μg/plate concentration. The mutation factor value was 1.35. However, there was no dose response, the observed mutation factor values were below the biologically relevant threshold limit and the numbers of revertant colonies were within the historical control range.

Higher numbers of revertant colonies compared to the solvent control were detected in the Initial Mutation Test and Confirmatory Mutation Test in some other sporadic cases. However, the numbers of revertant colonies were below the biologically relevant threshold value and they were within the historical control range, so they were considered as reflecting the biological variability of the test.

Lower revertant counts compared to the solvent control were observed in the Initial Mutation Test and Confirmatory Mutation Test in some sporadic cases with and without metabolic activation. The mean numbers of revertant colonies were in the historical control range, thus they were considered as biological variability of the test system.

Slight precipitate was detected on the plates in all examined strains in the Initial Mutation Test in the highest concentration with and without metabolic activation.

There was no insolubility or signs of inhibitory, cytotoxic effect of the test item in the Initial Mutation Test and the Confirmatory Mutation Test in any of the examined bacterial strains at any concentrations with or without metabolic activation.

Conclusions:

Interpretation of results (migrated information):
negative

Under the conditions of the test, the test item had no mutagenic activity

Executive summary:

The mutagenic potential has been assessed by exposure to S. typhimurium TA 1535, TA 1537, TA 98 and TA 100 and E. coli WP2 uvr A in DMSO, Distilled water and DMF with and without S9 metabolic activations in accordance with the OECD 471 test guideline in compliance with GLP. Under the conditions of the test, the test substance was shown to have no mutagenic activity to bacterium tester strains.

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
Data have been generated according to current internationally recognised study guidelines and in accordance with GLP

Justification for classification or non-classification

The mutagenic potential has been assessed by exposure to S. typhimurium TA 1535, TA 1537, TA 98 and TA 100 and E. coli WP2 uvr A in DMSO, Distilled water and DMF with and without S9 metabolic activations in accordance with the OECD 471 test guideline in compliance with GLP. Under the conditions of the test, the test substance was shown to have no mutagenic activity to bacterium tester strains.