N-(4-chlorophenyl)-3-hydroxy-4-[(2-methyl-5-nitrophenyl)azo]naphthalene-2-carboxamide

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Justification for type of information:

Data is from publication.

Data source

Reference

Reference Type:

publication

Title:

Macrocyclic musk compound an absence of genotoxicity in the Ames test and the in vivo Micronucleus assay

Author:

Lilianne Abramsson-Zetterberg , Premysl Slanina

Year:

2002

Bibliographic source:

Toxicology Letters 135 (2002) 155/163

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: Refer below principle

Principles of method if other than guideline:

Gene mutation toxicity study was performed to evaluate the mutagenic nature of the test compound Cyclopentadecanolide.

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Pentadecan-15-olide

EC Number:

203-354-6

EC Name:

Pentadecan-15-olide

Cas Number:

106-02-5

IUPAC Name:

oxacyclohexadecan-2-one

Constituent 2

Reference substance name:

Cyclopentadecanolide

IUPAC Name:

Cyclopentadecanolide

Test material form:

not specified

Details on test material:

- Name of test material: Cyclopentadecanolide/ Exactolide®
- Molecular formula: C15H28O2
- Molecular weight: 240.3842 g/mol
- Substance type: Organic
- Physical state: No data available
- Purity: 97%
- Impurities: 3%

Specific details on test material used for the study:

- Name of test material: Cyclopentadecanolide/ Exactolide®
- Molecular formula: C15H28O2
- Molecular weight: 240.3842 g/mol
- Substance type: Organic
- Physical state: No data available
- Purity: 97%
- Impurities: 3%

Method

Target gene:

Not applicable

Species / strain

Species / strain / cell type:

S. typhimurium, other: TA 97, TA 98, and TA 100

Details on mammalian cell type (if applicable):

Not applicable

Additional strain / cell type characteristics:

other: histidine auxotrophic strains

Cytokinesis block (if used):

No data

Metabolic activation:

with and without

Metabolic activation system:

Aroclor 1254 induced rat liver microsomal fraction S9

Test concentrations with justification for top dose:

Maximum concentration tested: 1.3 mg/plate

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: The test chemical was soluble in DMOS

Controls

Untreated negative controls:

not specified

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

benzo(a)pyrene

other: 2-aminofluorene

Details on test system and experimental conditions:

METHOD OF APPLICATION: Preincubation

DURATION
- Preincubation period: 20 mins
- Exposure duration: No data available
- Expression time (cells in growth medium): No data available
- 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: Duplicate

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

Rationale for test conditions:

No data

Evaluation criteria:

Increase in number of reversion mutants was noted

Statistics:

The two-tailed, Student t-test was used for a statistical evaluation of the results.

Results and discussion

Test results

Species / strain:

S. typhimurium, other: TA 97, TA 98, and TA 100

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:

TEST-SPECIFIC CONFOUNDING FACTORS
- Effects of pH: No data available
- Effects of osmolality: No data available
- Evaporation from medium: No data available
- Water solubility: No data available
- Precipitation: No data available
- Other confounding effects: No data available

RANGE-FINDING/SCREENING STUDIES: Provisional bacterial survival test was made before the Ames test in order to find out suitable compound concentrations.

COMPARISON WITH HISTORICAL CONTROL DATA: No data available

ADDITIONAL INFORMATION ON CYTOTOXICITY: No data available

Remarks on result:

other: No mutagenic potential

Applicant's summary and conclusion

Conclusions:

Exactolide® did not induce gene mutation in the Salmonella typhimurium bacterial strains TA 97, TA 98, and TA 100 both in the presence and absence of S9 metabolic activation system and hence is not likely to classify as a gene mutant in vitro.

Executive summary:

The macrocyclic musk cyclopentadecanolide was tested for gene toxicity in vitro in the Salmonella typhimurium strains TA 97, TA 98, and TA 100 both in the presence and absence of S9 metabolic activation system. The maximum concentration tested was 1.3mg/plate. The test chemical was dissolved in DMSO. Concurrent positive control chemicals were included in the study. Exactolide® did not induce gene mutation in the Salmonella typhimurium bacterial strains TA 97, TA 98, and TA 100 both in the presence and absence of S9 metabolic activation system and hence is not likely to classify as a gene mutant in vitro.