Registration Dossier

Administrative data

Description of key information

Isooctadecanoic acid is not irritating to the skin and not irritating to the eyes.

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

Justification for grouping of substances and read-across

In accordance with the specifications listed in Regulation (EC) No. 1907/2006 Annex XI, 1.5 Grouping of substances and read across, the similarity of category members has been shown to be justified based on the scope of variability and overlapping of composition, representative molecular structure, physico-chemical properties, tox-, ecotoxicological profiles and supporting Information by various validated QSAR methods. This information is given in further detail within the category justification for the grouping of chemicals and read-across (see IUCLID Section 13) for the dimerised fatty acids and its derivatives, and once more within the endpoint summary and discussion for Toxicokinetics.

For assessment of human health hazards of the category members, trends and similarities in toxicokinetic behaviour are most relevant. In particular, the molecular weight-dependent decrease in oral and dermal absorption and common metabolic pathways, which are explained by trends in molecular structure and common functional groups (monomers, dimers and trimers of similar long-chain fatty acids). This justifies the assumption that the toxicological profile of all category members is similar and effects or the lack of effects observed in toxicological studies of one ore more substances can also be expected and explained for the other substances in the category.

Therefore, in accordance with Annex XI, Item 1.5, of Regulation (EC) No 1907/2006, in order to avoid the need to test every substance for every endpoint, the category concept is applied for the assessment of human health hazards. Thus where applicable, human health effects are predicted from adequate and reliable data for reference substance(s) within the group by interpolation to other substances in the group (read-across approach).

All the available information from the substances within the category is taken into account for each endpoint to be assessed. Key studies are selected for assessment of the test substance and for read-across as to fulfil the requirements laid down in Annex XI, Item 1.5, of Regulation (EC) No 1907/2006, i.e. in all cases the results are adequate for the purpose of classification and labelling and/or risk assessment; have adequate and reliable coverage of the key parameters addressed in the corresponding test method referred to in Article 13(3); cover an exposure duration comparable to or longer than the corresponding test method referred to in Article 13(3) if exposure duration is a relevant parameter; and adequate and reliable documentation of the applied method is provided.

 

Discussion

Skin

The skin irritating potential of isooctadecanoic acid was assessed in a study conducted according to OECD Guideline 404 and in compliance with GLP. A volume of 0.5 mL of the test material was applied undiluted to the shaved skin of 3 New Zealand White rabbits for 4 hours under semiocclusive conditions. Slight reactional dryness together with decrease in skin suppleness was observed. Clear irritative phenomena were observed. They remained during 24 hours without any changes, and then decrease regularly. On day 6, not any irritation was seen, but slight changes in skin structure persisted until day 10. The mean erythema and edema scores over 24, 48 and 72 h for each individual animal were 1.3/1.3/1.0 and 0.7/0.7/0.7, respectively. Erythema was fully reversible within 6 days, while edema was fully reversible within 72 h (Saboureau, 1989).

In an earlier non-GLP study on primary skin irritation, the test material was applied both to intact and abraded skin of 6 rabbits for 24 h under occlusive conditions. No irritation effects were reported. Erythema and edema scores for the intact skin were both 0.0 at 24 and 72 h post-application (Wallace, 1976).

Data on isooctadecanoic acid have been previously reviewed as to its potential to induce primary skin irritation within a safety assessment of isooctadecanoic acid as cosmetic ingredient. Undiluted isooctadecanoic acid, 15% isooctadecanoic acid in corn oil and three product formulations were reported to have been assessed using the Draize rabbit skin patch test technique. An amount of 0.5 mL of the samples were applied and occluded for 24 h, after which time the patch sites were graded for erythema and edema on the Draize scale. According to the reported results, presented as primary irritation indices (PI), minimal irritation was induced by the undiluted ingredient (PI = 0.63 and 0.3), while no irritation was observed with the 15% dilution in corn oil (PI = 0.0). Isooctadecanoic acid in product formulations (at 1.25, 4 and 35%) induced minimal to moderate skin irritation (PI = 0.0 at 1.25%, 0.06 and 0.39 at 4%, 1.89 at 35%), which could also be mostly attributed to other ingredients found in the formulation (CIR, 1983).

In clinical studies, no signs of irritation were observed in 100 subjects after a 24-h single insult skin patch using undiluted isooctadecanoic acid. In other studies, isooctadecanoic acid was neither irritating nor sensitising when applied at concentrations of 10 and 35% in mineral oil to the skin of 103 and 168 subjects respectively (CIR, 1983).

Additionally, isooctadecanoic acid has been assessed in vitro in a skin integrity function test (SIFT) performed in compliance with GLP. 25 µl/cm² isooctadecanoic acid were applied to a mouse skin membrane placed in a glass diffusion cell for an exposure period of 20 h. The transepidermal water loss (TEWL) and the electrical resistance (ER) were measured in treated as well as in negative and positive control skin membranes prior to and after the 20 h exposure. According to the evaluation criteria described in the study report, test chemicals are classified as potentially irritant to skin if either the post application mean TEWL is > 10 g/m²/h or the mean post application ER is < 4 kΩ. Further, a correlation between the ER ratio (pre- to post-treatment) and the in vivo Draize scores was stated. Thus, an ER ratio between 0 and 3 is translated into “no irritation”. The test material gave a mean TEWL value of 6.24 and a mean ER value of 15.94. High ER values can result from the emollient properties of a test sample. The test material gave a mean ER ratio of 0.84 and, based on ER ratios values, was deemed not to be potentially irritant to skin (Johnson, 2006).

 

Eye

The eye irritating potential of the isooctadecanoic acid was investigated in a study conducted according to OECD Guideline 405 and in compliance with GLP. The test material (0.1 mL) was instilled into one eye of each of 3 New Zealand White rabbits, and the animals were observed at intervals for up to 72 h. A slight enanthema together with slight chemosis was observed in all 3 animals at the 1 hour reading. Enanthema remained during 48 hours in one animal and only 24 hours in the other two. Not any lesion of iris or cornea was recorded. The mean cornea and chemosis scores over 24, 48 and 72 h for all animals were both 0.0 (Boue-Grabot, 1989).

In an earlier non-GLP study on the toxicity of isooctadecanoic acid to eye mucosa, no signs of eye irritation were observed in rabbits after instillation of the test material into the conjunctival sac. Cornea, iris and chemosis scores were all 0.0 at 24, 48 and 72 h post-application in all animals (Wallace, 1976).

In addition, isooctadecanoic acid was reported to produce only minimal and transient eye irritation when instilled either undiluted or as a product formulation (2-35%) into the eyes of rabbits, without washing (CIR, 1983).

Justification for classification or non-classification

The available information on the skin and eye irritating potential of isooctadecanoic acid is conclusive but not sufficient for classification.