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

Endpoint summary

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 irritating to eyes and skin.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

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

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

The short exposure time of 15 minutes is thought not to impair the evaluation of the skin irritation potential significantly. As a 50% aqueous preparation is the limit of solubility, no higher concentrations would have been achieved if neat AH salt had been tested and this deviation from the test guideline is thought not to impair the evaluation of the skin irritation potential significantly.

Principles of method if other than guideline:

Before OECD Guideline 404 was established in 1982, skin irritation was tested using an internal method (BASF test). White Vienna rabbits were used. 2 animals were treated for 1, 5 and 15 minutes using occlusive conditions. An application site of 2.5 x 2.5 cm was covered with the liquid test substance on a patch. After the application time of 1, 5, and 15 minutes, respectively, the skin was first washed with undiluted Lutrol 9, then with an aqueous Lutrol solution (50 %). The skin of the animals that had been treated with the test substance for 20 hours, remained unwashed.

GLP compliance:

no

Remarks:

pre-GLP study

Species:

rabbit

Strain:

Vienna White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Breeder
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Photoperiod (hrs dark / hrs light): 12h/12h

Type of coverage:

occlusive

Preparation of test site:

clipped

Vehicle:

water

Controls:

other: not treated skin

Amount / concentration applied:

TEST MATERIAL
- Concentration (if solution): 50%; saturated solution; pH = 7.5

Duration of treatment / exposure:

1, 5 and 15 minutes

Observation period:

no data

Number of animals:

2

Details on study design:

TEST SITE
- Area of exposure: back, an application site of 2.5 X 2.5 cm was covered with the liquid (37°C; approx. 1 ml)

REMOVAL OF TEST SUBSTANCE
- Washing: yes, the sites were wiped with a mixture of acetic acid and polyethylene glycol (Lutrol) after the end of the exposure period.

SCORING
Descriptive scores of the raw data have been converted to Draize numerical scores.

Irritation parameter:

erythema score

Basis:

mean

Remarks:

n = 2

Time point:

other: unspecified

Score:

0

Max. score:

4

Reversibility:

other: no effects

Remarks on result:

other: short-time test with 1; 5; 15 min exposure

Irritation parameter:

edema score

Basis:

mean

Remarks:

n = 2

Time point:

other: unspecified

Score:

0

Max. score:

4

Reversibility:

other: no effects

Remarks on result:

other: short-time test with 1; 5; 15 min exposure

Irritant / corrosive response data:

None of two animals showed any effects of irritation at any application site.

primary dermal irritation index (PDII), mean of n=2: Score = 0

Limited documentation; no further details.

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the test conditions of this study, the test item, is considered as not irritating to the skin.

Executive summary:

In a skin irritation study (BASF, 1956), application of a saturated aqueous solution of the test substance (concentration ca. 50%) to the back of two rabbits for up to 15 minutes did not produce any signs of irritation. The short exposure time of 15 minutes is thought not to impair the evaluation of the skin irritation potential significantly. As a 50% aqueous preparation is the limit of solubility, no higher concentrations would have been achieved if neat AH salt had been tested and this deviation from the test guideline is thought not to impair the evaluation of the skin irritation potential significantly.

The primary dermal irritation index (PDII), mean of n=2: Score = 0. Based on these results, the test substance is considered as not irritating to the skin.

By analogy, sebacic acid, compound with hexane-1,6 -diamine (1:1) is not classified according to the CLP regulation 1272/2008/EC and the Directive 67/548/EC criteria.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

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

Adequacy of study:

key study

Study period:

no data

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Data on purity are lacking, but as there was no strong irritation observed, this is thought not to impair the evaluation of the eye irritation potential significantly. As a 50% aqueous preparation is the limit of solubility, no higher concentrations would have been achieved if neat AH salt had been tested and this deviation from the test guideline is thought not to impair the evaluation of the eye irritation potential significantly

Reason / purpose for cross-reference:

reference to other study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

limited documentation, 50 µl instead of 100 µl test substance instilled

Principles of method if other than guideline:

Not applicable.

GLP compliance:

no

Remarks:

pre-GLP study

Species:

rabbit

Strain:

Vienna White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Breeder
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Photoperiod (hrs dark / hrs light): 12h/12h

Vehicle:

water

Controls:

other: other eye of the same animals: treated with physiol. saline

Amount / concentration applied:

TEST MATERIAL
- Concentration (if solution): 50%

Duration of treatment / exposure:

instillation once without rinsing

Observation period (in vivo):

10 minutes, and 1, 3 and 24 hours

Number of animals or in vitro replicates:

2

Details on study design:

REMOVAL OF TEST SUBSTANCE
- The eye was left unwashed.
SCORING SYSTEM:
- Descriptive scores of the raw data have been converted to Draize numerical scores.

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

n = 2

Time point:

other: 24 h

Score:

0

Max. score:

4

Reversibility:

other: no effects

Irritation parameter:

iris score

Basis:

mean

Remarks:

n = 2

Time point:

other: 24 h

Score:

0

Max. score:

2

Reversibility:

other: no effects

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

n = 2

Time point:

other: 24 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 24 h

Remarks on result:

other: after 10 min and 1 to 3 hours mean score of 1

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

n = 2

Time point:

other: 24 h

Score:

0

Max. score:

4

Reversibility:

other: no effects

Irritant / corrosive response data:

Until 3 hours after administration of the test substance, very slight (equivalent to Draize score 0) and transient conjunctivitis was observed in both tested animals. All effects were completely reversible at 24 hours after instillation (no effects were observed in the control eyes treated with physiological saline).

Other effects:

No data

Limited documentation; no further details.

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the test conditions of this study, the test item is considered as not irritating to eyes. Thus, no classification is required according to EU criteria.

Executive summary:

In a primary eye irritation study (BASF, 1956), a 50% aqueous preparation of AH salt (limit of solubility) was instilled without rinsing into one eye of each of 2 rabbits (strain and sex not given). The eyes of 2 rabbits were examined 10 minutes, and 1, 3, and 24 hours after instillation of a 50% aqueous solution of the test substance into the right eye. The other eye served as control and was treated with physiological saline. The test material caused slight and transient conjunctivitis in two rabbits after exposure up to 3 hours. All effects were completely reversible within 24 hours.

A very slight and transient conjunctivitis was observed within the first 3 hours in both test animals. All eyes were normal at the 24 -hour reading. Therefore no readings were necessary to be done at 48 and 72 hours as required by the guideline.

As there were only very slight reactions after 3 hours and as no signs of irritation were observed after 24 hours, the test substance can be assumed to have no eye irritating properties.

Based on these results, the test item is considered as not irritating to eyes.

Thus, by analogy, no classification is required for sebacic acid, compound with hexane-1,6 -diamine (1:1), according to the Regulation (EC) 1272/2008 and the Directive 67/548/EEC criteria.

 

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

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 skin irritation / corrosion endpoint:
Only study available

Justification for selection of eye irritation endpoint:
Only study available

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 skin and eye irritation tests performed on this analogue, the substance sebacic acid, compound with hexane-1,6-diamine (1:1) is not classified for skin or eye irritation according to the regulation 1272/2008/EC criteria.