Fatty acids, C14-18 and C16-18-unsatd.

Endpoint summary

Description of key information

Irritation / corrosion:
- skin: not irritating (OECD 404, human data; Analogy CAS 57-10-3, CAS 57-11-4);
- eye: not irritating (OECD 405; Analogy CAS 143-07-7, CAS 57-10-3, CAS 57-11-4, CAS 90990-10-6);

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Additional information

Skin

Due to the lack of reliable data with fatty acids C14-18 and C16-18-unsatd. on skin irritation, studies with two of the main constituents, C16 fatty acid (palmitic acid) and C18 fatty acid (stearic acid), are used for hazard assessment. Since fatty acids C14-18 and C16-18-unsatd., palmitic acid and stearic 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).

Skin irritation by palmitic acid was evaluated in a study performed under GLP according to OECD guideline 404 with the exception, that the test was performed under occlusive condition (Kästner, 1988). Four Kleinrussen rabbits received an application of 0.5 g palmitic acid to the shaved skin under occlusion for 4 hours. The readings 24, 48, and 72 hours after application did not reveal any signs of irritation, thus resulting in mean scores of 0 for erythema and edema, respectively. As a consequence, test was cancelled due to welfare reasons. Based on the results, palmitic acid can be regarded as not irritating to skin.

In a study with human subjects, palmitic acid and 19 other substances were investigated with a closed epicutanous test. 10 µl of palmitic acid at a concentration of 50% was applied to the back of the volunteers for 24 hours using a Large Finn Chamber (Matthies, 1988). The reactions were scored for edema, erythema, scaling and fissures 1, 6, 24, 48, 72 and 144 hours after application. As result, for all readings the score 0 was found.

Skin irritation by stearic acid was evaluated in a study performed in accordance with federal guidelines (International Bio-Research, 1974). 0.5 mL of stearic acid was applied to the abraded skin of 6 New Zealand White rabbits under occlusion for 24 hours.at 24 and 72 hours after application revealed no signs of irritation. Although a longer application under occlusion than suggested according to actual guidelines, the resulting scores are 0, both for erythema and edema, respectively.

Due to the similar structural and toxicological properties of the members within the category including fatty acids C14-18 and C16-18-unsatd. and its main constituents palmitic acid and stearic acid, the same result is expected for fatty acids C14-18 and C16-18-unsat.. Thus, it is not irritating to skin.

Eyes

Due to the lack of reliable data with fatty acids C14-18 and C16-18-unsatd. on eye irritation, studies with three of the main constituents, C12 fatty acid (lauric acid), C16 fatty acid (palmitic acid) and C18 fatty acid (stearic acid) and a study with the analogue fatty acids C12-14 are used for hazard assessment. Since fatty acids C14-18 and C16-18-unsatd., lauric acid, palmitic acid and stearic 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).

Eye irritation by lauric acid was evaluated in a study performed under GLP according to OECD guideline 405, where 52.45 +/- 0.45 mg of lauric acid was instilled into the eyes of 3 New Zealand White rabbits (Daamen, 1989). The result mean scores for corneal opacity, iris, and conjunctival erythema and chemosis after 24 – 72 h were 0.9, 0.8, 2.9 and 1.6, respectively. While the effect on the iris and the edema disappeared within 7 and 21 days, respectively, corneal opacity and erythema were still present at the end of the 21 day observation period. In addition, neovacularisation starting from day 7 until day 21 was found. Thus, lauric acid was found to be irritating to eyes in this study. Fatty acids C12-14 containing 73.6% lauric acid was found to be not irritating to eyes, when it was tested in a study performed according to GLP and OECD guideline 405 where 0.1 g was instilled into the eyes of three New Zealand White rabbits (Stelter, 2010). While neither mortality nor significant clinical signs of toxicity were observed until 21 days after the test item application, the resulting mean scores (24 – 48 – 72 hours) for corneal opacity, iris, conjunctival erythema and chemosis were 0, 0, 0.78, and 0.67, respectively. Thus, lauric acid at a concentration of 73.6% was not found to be irritation to eyes.

Eye irritation by palmitic acid was analyzed in a study performed in accordance with GLP and according to OECD guideline 405 (Kästner, 1988). 0.1 g of palmitic was instilled into the rtights eyes of four Kleinrussen rabbits while the untreated left eyes served as control. The reactions were examined 1, 6, 24, 48, and 72 hour after administration and resulted in mean scores of 0, 0, 0.3, 0 and 0 for corneal opacity, iris, conjunctival redness and chemosis, and exudation, respectively. Since all signs were subsided on day three after instillation, the study was cancelled on that day due to animal welfare reasons. Based on the findings, palmitic acid can be regarded as not irritating to eyes.

In a published study performed according to national guidelines, stearic acid was instilled into the eyes of six rabbits (Briggs et al., 1976). Mild conjunctival erythema was found in 2 animals at 24 and 48 hours while all signs of irritation hat subsided completely in 72 hours. Thus, a mean score of 0.2 for conjunctival erythema could be calculated. Based on the results, stearic acid can be regarded as not irritating to eyes

Due to the structural and functional similarities of members within the category including fatty acids C14-18 and C16-18-unsatd. and its main constituents palmitic acid and stearic acid and the analogue fatty acids C12-14, the same result is expected for fatty acids C14-18 and C16-18-unsat. Thus, fatty acids C14-18 and C16-18-unsatd. are not irritating to eyes based on the contents of the individual constituents and their non-irritating properties.

Justification for classification or non-classification

The substance may contain few of lauric acid (C12), which is classified as R41/eye damage Cat 1. The specific concentration limit for the lauric acid is established as 73.6% based on a reliable experimental data. According to DPD (1999/45/EC) or CLP (1272/2008/EC) classification criteria for irritation/corrosion, fatty acids C14-18 and C16-18-unsatd. do not fulfill the criteria for classification and thus a non-classification is warranted for this endpoint as the concentration of C12 is lower than 73.6%.