Sebacic acid, compound with hexane-1,6-diamine (1:1)

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

By analogy with adipic acid, compound with hexane-1,6-diamine (1:1), the substance sebacic acid, compound with hexane-1,6-diamine (1:1) is not mutagenic in an ames test.

Link to relevant study records

Reference

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:

1980-01-15 to 1980-01-17 (experiment 1); 1980-02-02 to 1980-02-04 (experiment 2)

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable, well-documented study report which meets basic scientific principles. No test with S.typhimurium TA102 and/or E.coli; limited exposure concentration.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

not specified

GLP compliance:

no

Remarks:

Pre-GLP study.

Type of assay:

bacterial reverse mutation assay

Species / strain / cell type:

S. typhimurium, other: TA 1535, TA 1537, TA 1538, TA 98, TA 100

Metabolic activation:

with and without

Metabolic activation system:

Aroclor induced rat liver S-9

Test concentrations with justification for top dose:

4, 20, 100, 500, 2500 µg/plate

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: water

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: Cyclophosphamide, 2-aminoanthracene, N-methyl-N'-nitro-N-nitrososguanidine, 4-nitro-ophenylenediamine, 9-aminoacridinium chloride monohydratrate

Remarks:

positive control substance depending on the strain and activation condition

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation)

DURATION
- Exposure duration: 48 h (37°C)

NUMBER OF REPLICATESS: 4 plates per dose and control

DETERMINATION OF CYTOTOXICITY
- Method: decreased his- background growth

OTHER:
For better evaluation, the test was repeated with tester strain TA 100 with metabolic activation, only.

Evaluation criteria:

In general, a test substance has to be judged as positive, if the following criteria are fulfilled:
- doubling of the spontaneous mutation rate (control),
- dose-response relationship,
- reproducibility of results.

Species / strain:

S. typhimurium, other: TA 1535, TA 1537, TA 1538, TA 98, TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

No mutagenic activity (increase in the number of his+ revertants) and no bacteriotoxicity (decreased his- background growth) was observed at any concentration with any tester strain both with and without metabolic activation. For details, see attached files.

Conclusions:

Interpretation of results (migrated information):
negative (with and without metabolic activation).

Under the test conditions, hexamethylenediamine adipate was not mutagenic in the Ames test, when assayed at concentrations of up to 2500 µg/plate in the presence and absence of metabolic activation.

Executive summary:

In a reverse gene mutation assay in bacteria, performed similarly to the OECD No. 471 guideline, AH salt was tested in five Salmonella strains (TA 1535, TA 1537, TA 1538, TA 98, TA 100) both in the presence and in the absence of metabolic activation (liver S-9 mix) using the direct incorporation method (four plates per concentration for each strain) at 4, 20, 100, 500, 2500 µg/plate.

The positive controls induced appropriate responses in the corresponding strains.

Under the test conditions of this study, AH salt was not mutagenic in the Ames test up to 2500 µg/plate tested.

By analogy, sebacic acid, compound with hexane-1,6 -diamine, is considered negative in Ames test.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Additional information

Additional information from genetic toxicity in vitro:

READ-ACROSS JUSTIFICATION

When toxicological data required by REACH regulation are missing for sebacic acid, compound with hexane-1,6-diamine (1:1), read-across approach with adipic acid, compound with hexane-1,6-diamine (1:1) (CAS RN: 3323-53-3) is performed. This approach is justified by the information below:

1) Structural similarity

Both substances are acid compounds with hexane-1,6-diamine and therefore these acids have similar chemical structure.

As the difference between the 2 molecules is acids, the comparison is done between sebacic acid and adipic acid.

Both are linear diacids with structural formula of COOH-(CH2)₄-COOH for adipic acid and COOH-(CH2)₈-COOH for sebacic acid.

 

2) Similar physico-chemical properties

Below are the physic-chemical properties of both acids:

	Sebacic acid	Adipic acid
Melting point	135°C (exp)	150.85°C (exp)
Boiling point	> 420°C ; decomposes before boiling (exp)	337.5°C (published data)
Water solubility	224 mg/L at 25°C	23 g/L at 25°C
Vapour pressure	9x10E-6 Pa at 25°C	9.7 Pa at 18.5°C
Log kow	1.5 at 23°C and pH=3	0.093 at 25°C and pH=3.3
Flammability	Not flammable	Not flammable
Explosivity	Not explosive	Not explosive
Oxidizing properties	Not considered as oxidizing (SAR)	Not considered as oxidizing (SAR)

 

3) Similar toxicity potential

Both acid are:

- Not classified by oral route

- Not classified by dermal route

- Not classified for skin irritation

- Sebacic acid is slightly irritating to eyes and adipic acid causes serious eye damage

- Not classified for skin sensitization

 

To conclude, based on the similar chemical structure, physico-chemical properties and toxicity potential of diacids, the toxicity data obtained on adipic acid, compound with hexane-1,6-diamine (1:1) can be used to assess the toxicological profile of sebacic acid, compound with hexane-1,6-diamine (1:1). Data on adipic acid, compound with hexane-1,6-diamine (1:1) are used in a read-across approach in this dossier.

Justification for selection of genetic toxicity endpoint
Only study available
Acceptable, well-documented study report which meets basic scientific principles.

Justification for classification or non-classification

By analogy with adipic acid, compound with hexane-1,6-diamine (1:1) and based on the negative results obtained in an Ames test performed on this analogue, the substance sebacic acid, compound with hexane-1,6-diamine (1:1) is not classified for genetic toxicity according to the regulation 1272/2008/EC criteria.