Azelaic acid

Endpoint summary

Description of key information

Irritation/corrosion:
- skin: irritating (OECD 404; Analogy CAS 68937-75-5);
- eyes: irritating (national guideline; Analogy CAS 334-48-5);

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Additional information

Skin

In a range finding test as part of a sensitization study with guinea pigs performed according to OECD 406, azelaic acid was tested at concentrations of 1.0, 5.0, 10.0, 15.0, 25.0, 50.0 % for 24 under occlusive conditions. The readings 24 and 48 hours after removal of the patches did not reveal any signs of irritation of the skin for all concentrations tested. Thus, azelaic acid with concentration up to and including 50% is not irritating to skin.

However, due to lack of reliable data with pure azelaic acid on skin irritation, a study with the analogue fatty acids C8-10 is used for assessment. Since azelaic acid and fatty acids C8-10 belong to the same category based on structural and toxicological properties, this approach can be regarded as scientifically justified. Thus, read-across is performed based on a category approach (for details refer to IUCLID chapter 13).

Irritation to skin was evaluated in a study performed according to GLP and OEC guideline 404 and EU method B.4 (Daamen, 2000). Three female New Zealand White rabbits received a dermal application of 0.5 mL Fatty acid C8-10 to the shaved dorsal skin under semiocclusive conditions for 4 hours. No symptoms of systemic toxicity were observed in the animals during the 21 day observation period and no mortality occurred. However, although brown staining of the skin was caused by the test substance, the mean scores for 24 – 72 hours readings were found to be 3.3 and 3.7 for erythema and edema, respectively. Even at the end of the observation period, the effects were still evident. Based on these finding, fatty acids C8-10 have to be regarded as irritant to skin.

Due to the structural and functional similarities of members within the category including azelaic acid and fatty acids C8-10, the same result could be expected for azelaic acid. Together with the results of the range finding test for a sensitization study, azelaic acid has to be regarded as irritating to skin at concentrations higher than 50%.

 

Eyes

Due to lack of reliable data with azelaic acid on irritation to eyes, a study with the analogue C10 fatty acid decanoic acid is used for assessment. Since azelaic and decanoic acid belong to the same category based on structural and toxicological properties, this approach can be regarded as scientifically justified. Thus, read-across is performed based on a category approach (for details refer to IUCLID chapter 13).

In a published study performed according to national guidelines, decanoic acid was instilled into the eyes of six rabbits (Briggs, G.B. et al., 1976). Since corneal opacity and moderate conjunctivitis which did not subside in 72 h, the mean scores could be determined >2 for erythema and edema, respectively. Thus, decanoic acid can be regarded as irritating to eyes. Due to the structural and toxicological similarities of members within the category including azelaic acid and decanoic acid, the same result could be expected for azelaic acid.

Effects on skin irritation/corrosion: irritating

Effects on eye irritation: irritating

Justification for classification or non-classification

According to DSD (67/548/EEC) or CLP (1272/2008/EC) classification criteria for irritation/corrosion, azelaic acid has to be classified as irritating to skin (Xi, R38; Skin Cat. 2) at concentration higher than and including 50%.

According to DSD (67/548/EEC) or CLP (1272/2008/EC) classification criteria for irritation/corrosion, azelaic acid has to be classified as irritating to eyes (R36; Eye Cat. 2).

Based on the relaible experimenta data, the specific concentration limit (SCL) for skin irritating is established as 50% .