Registration Dossier

Administrative data

Description of key information

Skin irritation: not irritating (OECD 402, GLP)
Eye irritation: not irritating (OECD 437, GLP; OECD 405, GLP, read-across from structurally similar substances)

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion
Endpoint conclusion:
no study available

Eye irritation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for grouping of substances and read-across

There are no data available on the in vivo eye irritation potential of Fatty acids, C18-unsaturated, trimers, hydrogenated. In order to fulfil the standard information requirements set out in Annex VIII, Section 8.2.1, in accordance with Annex XI, Section 1.5 of Regulation (EC) No 1907/2006, read-across from structurally similar substances is conducted.

In accordance with Article 13 (1) of Regulation (EC) No 1907/2006, "information on intrinsic properties of substances may be generated by means other than tests, provided that the conditions set out in Annex XI are met.” In particular for human toxicity, information shall be generated whenever possible by means other than vertebrate animal tests, which includes the use of information from structurally related substances (grouping or read-across).

Having regard to the general rules for grouping of substances and read-across approach laid down in Annex XI, Item 1.5, of Regulation (EC) No 1907/2006, whereby physicochemical, toxicological and ecotoxicological properties may be predicted from data for reference substance(s) by interpolation to other substances on the basis of structural similarity, Fatty acids, C18-unsatd., dimers (CAS 61788-89-4) and Fatty acids, C18-unsatd., dimers, hydrogenated (CAS 68783-41-5) are selected as reference substances for assessment of in vivo eye irritation.

The read-across is based on structural similarity as a result of common origin and production process line. Shortly, the source and target substances are derived from catalytically di- and trimerised long-chain fatty acids; dimers and trimers are separated by distillation and unsaturated alkyl chains are hydrogenated as specifically required. A detailed analogue approach justification is provided in the technical dossier (see IUCLID Section 13).

Overview of irritation/corrosion

 

Target substance (a)

Source substance 1 (b)

Source substance 2

CAS No.

1373883-45-4

61788-89-4

68783-41-5

Chemical name

Fatty acids, C18-unsaturated, trimers, hydrogenated

Fatty acids, C18-unsatd., dimers

Fatty acids, C18-unsatd., dimers, hydrogenated

Skin irritation (in vivo)

Waiving

(Acute dermal toxicity limit dose study available)

Experimental result:

Not irritating

Experimental result:

Not irritating

Eye irritation/corrosion (in vitro)

Experimental result:

Not corrosive

--

--

Eye irritation/corrosion (in vivo)

WoE:

RA: CAS 61788-89-4

RA: CAS 68783-41-5

Experimental result:

Not irritating

Experimental result:

Not irritating

(a) The substance subject to the REACh Phase-in registration deadline of 31 May 2013 is indicated in bold font. Only for this substance a full set of experimental results and/or read-across is given.

(b) Reference (read-across) substances are indicated in normal font. Lack of data for a given endpoint is indicated by “--“.

Skin

The results of the available acute dermal toxicity study with Fatty acids, C18-unsaturated, trimers, hydrogenated (discussed under Acute toxicity) do not indicate skin irritation or corrosion up to the limit dose level (Bradshaw, 2013). Therefore, an in vivo skin irritation study does not need to be conducted according to Column 2 of Annex VIII, Section 8.1.1 of Regulation (EC) No 1907/2006, and the substance is thus considered to be not irritating to the skin.

Eye

In vitro eye corrosion / severe irritation

A Bovine Corneal Opacity and Permeability (BCOP) Assay was conducted with Fatty acids, C18-unsaturated, trimers, hydrogenated following OECD guideline 437 and under GLP conditions (Warren, 2012). The test material was applied undiluted to 3 equilibrated adult bovine corneas for 10 min followed by a 120-minute post-treatment incubation period. Negative (0.9% w/v sodium chloride solution) and positive (ethanol) control items were concurrently tested. Opacity was measured as the decrease in light transmission through the cornea prior to treatment, post-treatment and at the end of the post-treatment incubation period. Thereafter, permeability was determined photometrically as the increase in optical density at 492 nm (OD492) related to the passage of sodium fluorescein through the cornea after a 90- minute incubation with the dye. Corneal opacity and permeability were combined in an empirically derived formula to calculate an In Vitro Irritancy Score. A test item inducing an In Vitro Irritancy Score ≥ 55.1 was defined as an ocular corrosive or severe irritant.

The In Vitro Irritancy Scores for the test material, negative and positive controls were 1.1, 1.7 and 31.6, respectively. The positive control produced an In Vitro Irritancy Score which fell within two standard deviations of the historical mean for the testing facility, thus satisfying the positive control acceptance criterion.

Under the conditions of the study, the test material was considered not to be an ocular corrosive or severe irritant.

In vivo eye irritation

CAS 61788-89-4, CAS 68783-41-5

Fatty acids, C18-unsaturated, dimers and Fatty acids, C18-unsaturated, dimers, hydrogenated were tested for eye irritation in GLP-compliant studies according to OECD Guideline 405 and EU Method B.5, respectively (Mulder, 1986; Daamen, 1988). In each study, 0.1 mL of undiluted test material was applied into the conjunctival sac of one eye of each of 3 New Zealand White rabbits. Ocular reactions were evaluated at 1, 24, 48 and 72 h and until the observed effects had fully reversed. 

Fatty acids, C18-unsaturated, dimers induced slight conjunctival redness in all animals, as well as slight chemosis in two of the rabbits. Adverse effects on the cornea and the iris were not observed in any of the rabbits during the entire observation period. The mean conjunctivae and chemosis scores after 24, 48 and 72 h for each individual animal were 1.0/0.0/0.7 and 0.0/0.0/0.3, respectively. Conjunctival redness was fully reversible within 72-96 h and swelling within 48 h.

Fatty acids, C18-unsaturated, dimers, hydrogenated affected only the conjunctivae. One hour after instillation, all 3 animals showed diffuse redness of the palpebral conjunctivae and slight chemosis. Redness decreased to slight within 24 h in one animal and was no longer observed at the 72 h reading. In the remaining 2 animals, conjunctival redness decreased to slight within 48 h post-instillation and was fully reversible within 7 and 14 days, respectively. Slight chemosis persisted up to the 72 h reading and resolved between Day 3 and 7. No adverse effects on the cornea and the iris were observed in any of the rabbits during the entire observation period. The mean conjunctivae and chemosis scores over 24, 48 and 72 h for each individual animal were 1.3/1.3/0.7 and 1.0/1.0/1.0, respectively.

Based on the results of these studies, Fatty acids, C18-unsaturated, dimers and Fatty acids, C18-unsaturated, dimers, hydrogenated are not irritating to the rabbit eye.

Conclusions for irritation/corrosion

The substance Fatty acids, C18-unsaturated, trimers, hydrogenated has been tested for acute dermal toxicity. The results of the study do not indicate skin irritation or corrosion up to the limit dose level of 2000 mg/kg bw. Therefore, an in vivo skin irritation study does not need to be conducted according to Column 2 of Annex VIII, Section 8.1.1 of Regulation (EC) No 1907/2006, and the substance is thus considered to be not irritating to the skin.

An in vitro eye corrosion study (BCOP assay) is available for Fatty acids, C18-unsaturated, trimers, hydrogenated. The study results indicate that the substance is not an ocular corrosive or severe irritant.

There is no information available on in vivo eye irritation. Therefore, in order to fulfil the standard information requirements set out in Annex VIII, Section 8.2.1, in accordance with Annex XI, Section 1.5 of Regulation (EC) No 1907/2006, read-across from structurally similar substances is conducted.

The available in vivo eye irritation studies conducted with Fatty acids, C18-unsatd., dimers (CAS 61788-89-4) and Fatty acids, C18-unsatd., dimers, hydrogenated (CAS 68783-41-5) indicate that both substances are not irritating to the eyes.

Based on the available data, the substance Fatty acids, C18-unsaturated, trimers, hydrogenated is considered to be not irritating to the skin and eyes.


Justification for selection of skin irritation / corrosion endpoint:
No study required since the available acute toxicity study by the dermal route does not indicate skin irritation up to the limit dose level (2000 mg/kg bw), in accordance with Column 2 of Annex VIII, Section 8.1.1 of Regulation (EC) No 1907/2006.

Justification for selection of eye irritation endpoint:
Hazard assessment is conducted by means of read-across from structural analogues. All available studies are equally adequate and reliable based on the identified similarities in structure and intrinsic properties between source and target substances and overall quality assessment (refer to the endpoint discussion for further details).

Justification for classification or non-classification

Based on substance specific data and read-across from structurally similar substances following an analogue approach, the available data on the skin and eye irritating potential of the substance do not meet the classification criteria according to Regulation (EC) No 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.