1,8-Naphthalenediol, 1,8-dibenzoate

Genetic toxicity: in vitro

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline and GLP study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2014

Report date:

2014

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.5100 - Bacterial Reverse Mutation Test (August 1998)

GLP compliance:

yes (incl. QA statement)

Remarks:

testing lab.

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

8-(benzoyloxy)naphthalen-1-yl benzoate

EC Number:

810-797-4

Cas Number:

331711-99-0

Molecular formula:

C24 H16 O4

IUPAC Name:

8-(benzoyloxy)naphthalen-1-yl benzoate

Details on test material:

- Name of test material (as cited in study report): Thane 003-6
- Physical state: solid, beige to brown
- Analytical purity: approx. 98.153%
- Test substance No.: 13/0254-1
- Batch identification: LJ-008-09-136
- Storage condition of test material: Room temperature (protected against humidity)
- Homogeneity: ensured by mixing before preparation of test substance solutions
- Storage stability: The stability of the test substance under storage conditions throughout the study period was guaranteed until 30 Jun 2016 as indicated by the sponsor, and the sponsor holds this responsibility.

Method

Target gene:

Salmonella typhimurium: histidine
Escherichia coli WP2 uvrA: tryptophan

Species / strain

Species / strain 1

Species / strain / cell type:

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

Species / strain 2

Species / strain / cell type:

E. coli WP2 uvr A

Metabolic activation:

with and without

Metabolic activation system:

phenobarbital/b-naphtoflavone

Test concentrations with justification for top dose:

Standard plate test and Preincubation test: 0; 33; 100; 333; 1 000; 2500 and 5000 μg/plate

Vehicle / solvent:

The test substance was dissolved in DMSO. To achieve a clear solution of the test substance in the vehicle, the test substance preparation was treated with ultrasonic waves and shaken thoroughly. The further concentrations were diluted according to the planned doses. All test substance formulations were prepared immediately before administration.

Controls

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

4-nitroquinoline-N-oxide

9-aminoacridine

N-ethyl-N-nitro-N-nitrosoguanidine

other: 2-aminoanthracene (with S9 mix), 4-nitro-o-phenylenediamine (without S9 mix)

Remarks:

with S9 mix: 2-AA (all strains); without S9 mix: MNNG (TA 1535, TA100), NOPD (TA 98), AAC (TA 1537), 4-NQO (E. coli)

Details on test system and experimental conditions:

1st Experiment
Strains: TA 1535, TA 100, TA 1537, TA 98, E. coli WP2 uvrA
Doses: 0; 33; 100; 333; 1 000; 2 500 and 5 000 μg/plate
Type of test: Standard plate test with and without S9 mix
Number of plates: 3 test plates per dose or per control

2nd Experiment
Strains: TA 1535, TA 100, TA 1537, TA 98, E. coli WP2 uvrA
Doses: 0; 33; 100; 333; 1 000; 2 500 and 5 000 μg/plate
Type of test: Preincubation test with and without S9 mix
Number of plates: 3 test plates per dose or per control
Reason: No mutagenicity was observed in the standard plate test.

3rd Experiment
Strains: TA 98
Doses: 0; 33; 100; 333; 1 000; 2 500 and 5 000 μg/plate
Type of test: Preincubation test with and without S9 mix
Number of plates: 3 test plates per dose or per control
Reason: Due to contaminations observed in the Preincubation test with TA 98 an evaluation of this tester strain was not possible. The 2nd Experiment with TA 98 was not reported.

Evaluation criteria:

Individual plate counts, the mean number of revertant colonies per plate and the standard deviations were given for all dose groups as well as for the positive and negative (vehicle) controls in all experiments. In general, six doses of the test substance were tested with a maximum of 5 mg/plate, and triplicate plating was used for all test groups at least in the 1st Experiment. The titer was generally determined only in the experimental parts with S9 mix both for the negative controls (vehicle only) and for the two highest doses in all experiments. Toxicity detected by a decrease in the number of revertants, clearing or diminution of the background lawn, or reduction in the titer. Toxicity was recorded for all test groups both with and without S9 mix in all experiments. Precipitation of the test material was recorded and as long as it did not interfere with the colony scoring, 5 mg/plate was generally selected and analyzed as the maximum dose to detect possible mutagenic impurities.

Results and discussion

Test results

Test results 1

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:

cytotoxicity

Remarks:

starting at 1000 ug/plate (standard plate test) or 2500 µg/plate (in preincubation test)

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Test results 2

Species / strain:

E. coli WP2 uvr A

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

starting at 1000 ug/plate (standard plate test) or 2500 µg/plate (in preincubation test)

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

No increase in bacterial reverse mutants was observed with Thane 003-6, either in the standard plate test or the preincubation test. Precipitation of the test substance was found starting at 333 ug/plate with and without S9 mix.