Azelaic acid, calcium salt (1:1)

Endpoint summary

Description of key information

The skin sensitisation potential of calcium azelate has been read across from the structural analogue, dilithium adipate, which was assessed in an in vivo study conducted in accordance to OECD guideline 429. At test item concentrations of 2, 15 and 30%, the SI were 1, 0.9 and 0.6, and the EC3 was >30. The substance would not be regarded as a skin sensitizer.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

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

Adequacy of study:

key study

Study period:

2015

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: This study is carried out in accordance to OECD guideline 429, EU method B.42 and is GLP compliant. Therefore, it is given reliability rating of 1 (reliable without restrictions).

Justification for type of information:

Please see attached read across justification for full details of the read across approach.

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)

Qualifier:

according to guideline

Guideline:

EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)

GLP compliance:

yes (incl. QA statement)

Type of study:

mouse local lymph node assay (LLNA)

Species:

mouse

Strain:

CBA

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Janvier, Le Genest-Saint-Isle, France
- Age at study initiation: Approximately 10 weeks old
- Weight at study initiation: Body weight variation was within +/- 20% of the sex mean.
- Housing: Makrolon cages containing sterilised sawdust
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-24
- Humidity (%): 40-70
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

acetone/olive oil (4:1 v/v)

Concentration:

2, 15 and 30 % test item w/w

No. of animals per dose:

5

Details on study design:

RANGE FINDING TESTS: 15 and 30 % test item w/w using 2 animals per concentration

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: 6 days
- Test groups: 5 animals exposed to each concentration
- Control group: 5 animals exposed to the vehicle
- Site: dorsal surface of both ears
- Frequency of applications: Days 1, 2, 3
- Duration: 6 days
- Concentrations: 2, 15 and 30 % test item w/w

SCORE:
Erythema and eschar formation:
No erythema - 0
Very slight erythema (barely perceptible) - 1
Well-defined erythema - 2
Moderate to severe erythema (beet redness) to slight eschar formation (injuries in depth) - 3
Severe erythema (beet redness) to eschar formation preventing grading of erythema - 4

Positive control substance(s):

other: No

Positive control results:

A reliability check is carried out at regular intervals to check the sensitivity of the test system and the reliability of the experimental techniques used at the laboratory. The last check was performed in April 2015. The SI values calculated for the item concentrations 5, 10 and 25% were 1.7, 3.0 and 9.1 respectively. An EC3 value of 10% was calculated using linear interpolation. The calculated EC3 value was found to be in the acceptable range of 4.8 and 19.5%. The results of the 6 monthly HCA reliability checks of the recent years were 16.5, 14.5, 13.4, 14.1, 17.3 and 9.8%. Based on the results, it was concluded that the Local Lymph Node Assay as performed at the laboratory is an appropriate model for testing for contact hypersensitivity.

Parameter:

SI

Value:

1

Test group / Remarks:

Test item concentration = 2%

Parameter:

SI

Value:

0.9

Test group / Remarks:

Test item concentration = 15%

Parameter:

SI

Value:

0.6

Test group / Remarks:

Test item concentration = 30%

Parameter:

EC3

Value:

> 30

No irritation and no signs of systemic toxicity were observed in any of the animals.

No mortality occurred and no clinical signs of systemic toxicity were observed in the animals of the main study. Body weights and body weight gain of experimental animals remained in the same range as controls over the study period.

All auricular lymph nodes of the animals of the experimental and control groups were considered normal in size.

No macroscopic abnormalities of the surrounding area were noted for any of the animals.

Mean DPM/animal values for the experimental groups treated with test item concentrations 2, 15 and 30% were 899, 780 and 584 DPM, respectively. The mean DPM/animal value for the vehicle control group was 911 DPM. The SI values calculated for the item concentrations 2, 15 and 30% were 1.0, 0.9 and 0.6, respectively.

Interpretation of results:

GHS criteria not met

Conclusions:

Dilithium adipate would not be regarded as a skin sensitizer.

Executive summary:

This study is carried out in accordance to OECD guideline 429, EU method B.42 and is GLP compliant. Therefore, it is given reliability rating of 1 (reliable without restrictions). Dilithium adipate would not be regarded as a skin sensitizer.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

The skin sensitisation potential of calcium azelate has been read across from the structural analogue, dilithium adipate. The substance does not meet the criteria for classification as a skin sensitizer.