Registration Dossier

Administrative data

Description of key information

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Justification for read-across from fatty acids, tall-oil (CAS No. 61790-12-3)

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 and 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.

For the endpoint skin sensitisation, within the chemical categoryDimerised Fatty Acids and its Derivatives, limited information is available for fatty acids, C18-unsaturated, trimers (CAS No. 68937-90-6) and isooctadecanoic acid (CAS No. 30399-89-4). This information is discussed further below. Additionally, available information on pure C16-C18 monomeric fatty acids was also taken into account for assessment.

Furthermore, a skin sensitisation study (Guinea Pig Maximisation Test) with fatty acids, tall-oil(CAS No. 61790-12-3),is available.

On the basis of Annex XI, Item 1.5, of Regulation (EC) No 1907/2006, whereby human health effects may be predicted from data for a reference substance, provided that the physicochemical, toxicological and ecotoxicological properties of the reference and target substances are likely to be similar as a result of structural similarity,read-across from the surrogate substance fatty acids, tall-oil (CAS No. 61790-12-3) is conducted and the aforementioned study is selected as a key study for assessment of potential skin sensitising effects of the members of the category Dimerised Fatty Acids and its Derivates.

The similarities between fatty acids, tall-oil and the category members are based on the following considerations:

The Dimerised Fatty Acids and its Derivates category includes the following members:

61788-89-4 Fatty acids, C18-unsaturated, dimers, “Dimer”

68937-90-6 Fatty acids, C18-unsaturated, trimers, “Trimer”

68783-41-5 Fatty acids, C18-unsaturated, dimers, hydrogenated, “Hydrogenated dimer”

71808-39-4 Fatty acids, C16-18 and C18 unsaturated, dimerized, “Crude dimer”

68955-98-6 Fatty acids, C16-18 and C18-unsaturated, branched and linear, “Monomer acid”

68201-37-6 Octadecanoic acid, branched and linear, “Hydrogenated monomer acid”

30399-84-9 Isooctadecanoic acid

All the members of this category of substances are derived from unsaturated fatty acids, for example from fatty acids, tall-oil, which contains predominantly C18 unsaturated and saturated fatty acids. 

Natural fatty acids, tall-oil has the following properties:

Chemical name: Fatty acids, tall-oil

Chemical formula: not available - UVCB substance

EC No.: 263-107-3

CAS Name: Fatty acids, tall-oil

CAS number: 61790-12-3

logKow: determined range 4.9 – 7.6 (Lightbody et al., 2002)

Solubility in water (mg/L, at 20 °C): 12.6 (The quoted value represents the sum solubility of all the components of the test material) (Dinwoodie, 2004)

Biodegradation at 28 days: 56-84% (Madsen, 1993; Aniol, 1999; Sewell, 1994)

The HPV report final submission for fatty acids, tall-oil and related substances; CAS No. 61790-12-3 CAS No. 65997-03-7 CAS No. 68955-98-6 CAS No. 68201-37-6 CAS No. 61790-44-1 CAS No. 61790-45-2 Submitted to the US EPA August 2004 was screened by the US EPA and a screening level hazard characterisation report was published in 2007 (U. S. Environmental Protection Agency, 2007). This report prepared by the High Production Volume Chemicals Branch indicated that fatty acids, tall-oil are non-toxic following acute oral exposure (LD50 (rat) > 10000 mg/kg bw) and following a 90-day test in rats the No Observed Effect Level (NOEL) was 5% (approximately 2500 mg/kg bw/day). Fatty acids, tall-oil were negative in an Ames test with 5 S. typhimurium strains and in an in vitro chromosomal aberration assay with Chinese Hamster Ovary cells. In a Two-Generation Reproduction Toxicity study in rats, the NOEL for reproduction and systemic toxicity was 10% in diet (ca. 5000 mg/kg bw/day). Furthermore, fatty acids, tall-oil were not acute toxic in fish (96 h NOELr 1000 mg/L), daphnia (48 h NOELr 1000 mg/L) and algae (72 h NOELr 845 mg/L).

Given their chemical nature, fatty acids, tall-oil are expected to be absorbed, metabolised and excreted following the same well-known pathways of dietary fatty acids.

In conclusion, the physicochemical, toxicological and ecotoxicological properties of fatty acids, tall-oil and the members of the category Dimerised Fatty Acids and its Derivates are considered to be similar, and similarity is based on common functional groups (long-chain fatty acids, saturated and unsaturated) and the likelihood of common breakdown products via the metabolism of fatty acids. It is therefore considered appropriate that the skin sensitisation data of fatty acids, tall-oil is used for read-across purposes to this category.

The selected study fulfils the requirements laid down in Annex XI, Item 1.5, of Regulation (EC) No 1907/2006 for read-across, i.e. 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); and adequate and reliable documentation of the applied method is provided.

 

Skin sensitisation

The skin sensitising potential of fatty acids, tall-oil (CAS No. 61790-12-3) was studied in a Guinea Pig Maximisation Test according to OECD Guideline 406 and in compliance with GLP. The study was performed on 30 Dunkin-Hartley guinea pigs divided into a negative control group of 10 animals and a test group of 20 animals. The test comprised induction and challenge phases.

Induction was carried out by intradermal injection of the test material at 6.25% (w/w) in coconut oil and by closed patch topical application at 25% (w/w) in coconut oil for 48 h one week apart. The negative control group was treated with coconut oil.

All animals were challenged 3 weeks after the intradermal induction by closed patch topical application of the test material at 12.5% (w/w) in coconut oil for 24 h on the left flank. The skin reactions were evaluated 24 and 48 h after termination of the challenge procedure.

No skin reactions were observed 24 and 48 h after the challenge procedure.

A positive control test was also performed using undiluted hexyl cinnamic aldehyde for induction and at 12.5% (w/w) in ethanol/diethylphthalate 1:1 (w/w) for challenge, under experimental conditions similar to those described above. Evidence of delayed contact hypersensitivity was seen in 6 out of 10 animals (60%).

Under the experimental conditions described, it was concluded that no evidence of delayed contact hypersensitivity reaction was seen after treatment with fatty acids, tall-oil (Bollen, 1998).

The skin sensitising potential of fatty acids, C18-unsaturated, trimers (CAS No. 68937-90-6) was assessed in two independent Buehler Tests. Both studies involved the treatment of guinea pigs (20 animals per concentration) using two procedures: the potential induction of an immune response and a challenge of that response. Three inductions with the undiluted test substance were performed. Animals were challenged with the test substance at 0, 50 and 75% w/v in corn oil. The sensitisation response of the animals was determined 1 and 2 days after challenge, by assessing the degree of erythema.

In one study, all animals treated with the 50% dilution showed no effects, while in 2/20 (10%) animals in the 75% group mild sensitising effects were observed at both the 24 and 48 h reading time points. In the other study, the test substance induced no effects in any animal at any time (Johnson, 2000a, b).

Isooctadecanoic acid (CAS No. 30399-84-9) as well as palmitic (C16), oleic and stearic (both C18) acids have been assessed with respect to their safety as cosmetic ingredients, and tested for skin sensitisation in a number of clinical 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. No evidence of contact sensitisation was observed in 333 subjects tested in repeated insult patch tests using product formulations containing 2.5-2.85% isooctadecanoic acid (CIR, 1983). In clinical repeated insult patch tests (occlusive, semi-occlusive and open), maximisation tests as well as prophetic patch tests using cosmetic product formulations containing palmitic, stearic and oleic acids at concentrations between < 1 and 13%, no primary or cumulative irritation or sensitisation was reported. Less than 5% of the ca. 4000 subjects tested reacted to a few, isolated induction patches. Slight, if any, reactions were noted after challenge patching at the original or adjacent applications sites of some subjects (< 2%). The intensity of the observed reactions was not directly related to the fatty acid concentrations in the product formulations (CIR, 1987).

In addition, the skin sensitising potential of isooctadecanoic acid was estimated by means of QSAR analysis. Structural alerts were examined by means of the OECD QSAR Application Toolbox databases. Alternatively, the record of the substance in the Danish EPA QSAR Database was examined. The model applied for skin sensitisation was MULTICASE model A33. No structural alerts were detected in the molecule of the substance, hence the result was negative. The result of the Multicase model was negative as well. Based on the absence of relevant structural alerts, and the result recorded in the QSAR database, the chemical is considered not sensitising.

Taken together, the information available on structurally related substances indicates that fatty acids, C16-C18 and C18 unsaturated, branched and linear are unlikely to induce skin sensitisation.


Migrated from Short description of key information:
Based on read-across from supporting substance (surrogate fatty acids, tall-oil) and information on further structurally related substances, fatty acids, C16-C18 and C18 unsaturated, branched and linear are not skin sensitising.

Justification for classification or non-classification

Based on read-across from a supporting substance (surrogate fatty acids, tall-oil) and information on further structurally related substances, the available information on the skin sensitising potential of fatty acids, C16 -C18 and C18 unsaturated, branched and linear is conclusive but not sufficient for classification.