Nitric acid, reaction products with cyclododecanol and cyclododecanone, by-products from, high-boiling fraction

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

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

Adequacy of study:

key study

Study period:

1999-10-05 to 1999-10-22

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1999

Report date:

1999

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Principles of method if other than guideline:

Directive 92/69/EEC, B.14

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Dodecanedioic acid

EC Number:

211-746-3

EC Name:

Dodecanedioic acid

Cas Number:

693-23-2

Molecular formula:

C12H22O4

IUPAC Name:

dodecanedioic acid

Constituent 2

Reference substance name:

Dodecandioic Acid

IUPAC Name:

Dodecandioic Acid

Details on test material:

Dodecanedioic acid of Creanova Spezialchemie GmbH, batch no. 73. Purity not reported here; 99.4 % according to other test reports

Method

Target gene:

mutated gene loci responsible for histidine auxotrophy

Species / strain

Species / strain / cell type:

other: Salmonella typhimurium TA 1535, TA 1537, TA 98, TA 100, TA 102

Metabolic activation:

with and without

Metabolic activation system:

Phenobarbital / beta-naphthoflavone co-induced rat liver S9 fraction

Test concentrations with justification for top dose:

313; 625; 1250; 2500; 5000 µg/plate (+/- metabolic  activation)

Vehicle / solvent:

dimethyl sulfoxide (DMSO)

Controls

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

Remarks:

dimethyl sulfoxide (DMSO)

True negative controls:

yes

Positive controls:

yes

Positive control substance:

other: without S9 sodium azide (TA 1535, TA 100); 9-aminoacridine (TA 1537); cumene hydroperoxide (TA 102); 2-nitrofluorene (TA 98) with S9: 2-aminoanthracene

Details on test system and experimental conditions:

Ames test
SYSTEM OF TESTING
- Metabolic activation system:    Phenobarbital / beta-naphthoflavone co-induced rat liver S9 fraction,  batch 99/7, 
prepared from male Sprague-Dawley rats
ADMINISTRATION: 
- Dosing:    Preliminary toxicity test (1 replicate): 50; 158; 500; 1580; 5000  µg/plate (+/- metabolic activation)   
Plate incorporation test: 313; 625; 1250; 2500; 5000 µg/plate (+/-  metabolic activation)   repeated for TA 102 (+/- metabolic activation) due to 
gross bacterial  contamination of all plates prepared with this strain   
Pre-incubation test: 313; 625; 1250; 2500; 5000 µg/plate (+/- metabolic  activation)
- Number of replicates: 3
- Application: Solvent dimethyl sulfoxide (CAS No. 67-68-5)
- Positive and negative control groups and treatment:    
positive, TA 1535: 1 µg sodium azide/plate (- S9) / 1 µg  2-aminoanthracene/plate (+ S9)   
positive, TA 1537: 50 µg 9-aminoacridine/plate (- S9) / 1 µg  2-aminoanthracene/plate (+ S9)   
positive, TA 102: 100 µg cumene hydroperoxide/plate (- S9) / 10 or 20  µg 2-aminoanthracene/plate (+ S9)   
positive, TA 98: 2 µg 2-nitrofluorene/plate (- S9) / 1 or 2 µg  2-aminoanthracene/plate (+ S9)   
positive, TA 100: 1 µg sodium azide/plate (- S9) / 1 or 2 µg  2-aminoanthracene/plate (+ S9)   
negative: untreated / solvent control (100 µl/plate) (pre-incubation:  50 µl/plate)   
sterility control including positive control   
activity of metabolic system: 2-aminoanthracene and benzo(a)pyrene / TA  100
- Pre-incubation: 30 minutes at 37 °C   incubation approximately 72 hours at 37 °C

Evaluation criteria:

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

Results and discussion

Test results

Species / strain:

S. typhimurium, other: strains TA 1535, TA 1537, TA 98, TA 100, TA 102

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

other: No toxicity at <= 5000 µg/plate (= highest dose level)

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

GENOTOXIC EFFECTS: 
- With metabolic activation: None
- Without metabolic activation: None   
The positive controls were functional.
PRECIPITATION CONCENTRATION: The solubility of the test substance in DMSO  was initially determined to be 100 mg/ml.

Remarks on result:

other: other: Salmonella typhimurium TA 1535, TA 1537, TA 98, TA 100, TA 102

Remarks:

Migrated from field 'Test system'.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative

No genotoxic effects in a battery of microbial tester strains in the presence or absence of metabolic activation.

Executive summary:

The test substance dodecanedioic acid was examined for mutagenic activity by assaying for reverse mutation to histidine prototrophy in the prokaryotic organism Salmonella typhimurium.tester strains TA1535, TA1537, TA98, TA100 and TA102. Experiments were performed both in the absence and presence of metabolic activation, using liver S9 fraction from rats pre-treated with phenobarbitone and betanaphthoflavone. Test substance solutions were prepared using dimethylsulphoxide.

No toxicity was observed with any tester strain in the toxicity test with a maximum dose-level of 5000µg/plate.

Using the plate incorporation method, and in a subsequent independent assay the preincubation method the test substance was assayed at a maximum dose-level of 5000 µg/plate and at 2500, 1250, 625 and 313 µg/plate.

The test substance did not induce two-fold increases in the number of revertantcolonies in the plate incorporation or pre-incubation assay, at any dose-level, in any tester strain, in the absence or presence of S9 metabolism.