3-cyano-3,5,5-trimethylcyclohexanone

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

Study period:

September 1990

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Guideline study with acceptable restrictions: Both TA 102 and E.coli WP2 were not tested (not required by applied version of guideline).

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1990

Report date:

1990

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

3-cyano-3,5,5-trimethylcyclohexanone

EC Number:

411-490-4

EC Name:

3-cyano-3,5,5-trimethylcyclohexanone

Cas Number:

7027-11-4

Molecular formula:

C10H15NO

IUPAC Name:

3-cyano-3,5,5-trimethylcyclohexanone

Details on test material:

Isophorone nitrile of Degussa AG. Batch No. 64-II/78/90. Purity 99.6 % (GC).

Method

Target gene:

mutated gene loci responsible for histidine auxotrophy

Species / strain

Species / strain / cell type:

other: Salmonella typhimurium TA 1535, TA 1537, TA 1538, TA 98, TA 100

Additional strain / cell type characteristics:

other: histidine auxotroph

Metabolic activation:

with and without

Metabolic activation system:

Aroclor 1254-induced rat liver S9 fraction, prepared from male Wistar  rats (Crl:WI (WU)BR)

Test concentrations with justification for top dose:

0.31; 0.93; 2.78; 8.33; 25.0 mg/plate

Vehicle / solvent:

DMSO dimethyl sulfoxide (CAS No. 67-68-5)

Controls

Untreated negative controls:

yes

Remarks:

untreated

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

True negative controls:

no

Positive controls:

yes

Remarks:

with and without metabolic acvtivation

Positive control substance:

9-aminoacridine

Remarks:

different positive control substances without metabolic activation, see below

Migrated to IUCLID6: all strains with metabolic activation

Details on test system and experimental conditions:

Ames test
SYSTEM OF TESTING
- Metabolic activation system:    Aroclor 1254-induced rat liver S9 fraction, prepared from male Wistar  rats (Crl:WI (WU)BR)
ADMINISTRATION: 
- Dosing:    Dose range initially determined in a cytotoxicity test with up to 25  mg/plate.   
Test doses 0.31; 0.93; 2.78; 8.33; 25.0 mg/plate (+/- metabolic  activation)
- Number of replicates: 3
- Application: solvent dimethyl sulfoxide (DMSO, CAS No. 67-68-5)
- Positive and negative control groups and treatment:    
positive without metabolic activation:   
TA 1535, TA 100: 1.0 µg sodium azide/plate   
TA 1538, TA 98: 2.0 µg 2-nitrofluorene/plate   
TA 1537: 80 µg 9-aminoacridine/plate   
positive with metabolic activation:   
all strains: 2 µg (TA 1537: 5 µg) 2-aminoanthracene/plate   
negative: untreated   
activity of metabolic system: 2-aminoanthracene and 4-aminobiphenyl in  TA 98
- Pre-incubation: no   incubation 3 days at 37 °C
DESCRIPTION OF FOLLOW UP REPEAT STUDY: Repeat study for confirmation of  results with identical test conditions

Evaluation criteria:

CRITERIA FOR EVALUATING RESULTS:    ratio of revertant rates treated/control >= 2 with generally positive  dose-response relationship in any 
strain in two independent experiments

Statistics:

usual statistical methods (standard deviation; means; factors)

Results and discussion

Test results

Species / strain:

other: Salmonella typhimurium TA 1535, TA 1537, TA 1538, TA 98, TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Remarks:

No cytotoxicity was observed.

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

GENOTOXIC EFFECTS: None (initial and repeat study)
PRECIPITATION CONCENTRATION: No precipitation was observed.

Remarks on result:

other: other: Salmonella typhimurium TA 1535, TA 1537, TA 1538, TA 98, TA 100

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

no further remarks

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative

Under the conditions of the study the test item isophorone nitrile proved to be non-mutagenic, both in the presence and in the absence of Arochlor-induced liver microsomes, for all test strains used in this study.

Executive summary:

The substance isophorone nitrile was tested in the Ames Salmonella mutagenicity test for any mutagenic activity. The test organisms were five histidine-auxotrophic Salmonella typhimurium strains (TA 1535; TA 1537; TA 1538; TA 98 and TA 100). Under the conditions of the study the test item isophorone nitrile proved to be non-mutagenic, both in the presence and in the absence of Arochlor-induced liver microsomes, for all test strains used in this study.