Hexadecanedioic acid

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Study period:

1999-10-05 to 1999-10-22

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

1. HYPOTHESIS FOR THE CATEGORY APPROACH (ENDPOINT LEVEL)
Dicarboxylic acids are organic compounds that contain two carboxylic acid functional groups. They have the general type formula HOOC-(CH2)n-COOH. The present defined category comprises dicarboxylic acids with straight carbon chain having a “n” value from 6 to 16.
The physical and chemical properties as well as the toxicology and environmental fate and effects show that substances in this category have a similar order of toxicological and environmental fate properties, which supports the grouping of these substances as a category. (see attached justification)

2. CATEGORY APPROACH JUSTIFICATION (ENDPOINT LEVEL)
There are number of unifying considerations justifying the similarity between these substances in some important aspects. These include:
(1) Similarity of Use: these dicarboxylic acids have several industrial uses in the production of adhesives, plasticizers, lubricants, copolymers (such as polyamides and polyesters), etc.
(2) Similarity of Functional groups: all these substances contain two common functional groups (2 carboxyl groups). The only difference between the substances of this group lies in the length of the carbon chain.
(3) Similarity of Physical / Chemical properties: the similarity of physical / chemical properties for these substances (see attached justification)
(4) Similarity of Metabolism: Dicarboxylic acids were shown to be rapidly absorbed from the gastrointestinal tract, introduced into the fatty acid catabolism and therefore extensively metabolized by the organism and excreted (Passi, S. et al, 1983).
(5) Similarity of Mammalian Toxicity: The constituents of this class have similar toxicological properties. They are not acutely toxic, irritating to skin or sensitizing. However, they all present, except for dodecanedioic acid, irritating effects on the eyes (from moderate to high effects). They do not produce systemic effects in repeated dose studies. They are neither mutagenic nor carcinogenic and do not produce developmental/reproductive toxicity. (see attached justification)
(6) Similarity of Environmental Toxicity and Fate Properties: The substances in this category have similar environmental effects properties. The environmental effects data are similar for most category members in that most members do not exhibit acute toxicity. (see attached justification)

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)

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

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:

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

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 TA 1535, TA 1537, TA 98, TA 100 and 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 were detected for dodecanedioic acid in a battery of microbial tester strains in the presence or absence of metabolic activation. Based on a read across (category approach), no classification regarding the genetic toxicity is required for hexadecanedioic acid.