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 grouping of substances and read-across

The long-chain aliphatic ester (LCAE) category covers mono-esters of a fatty acid and a fatty alcohol. The category contains both mono-constituent and UVCB substances. The fatty acid carbon chain lengths range is C8 - C22 (even and uneven numbered, including saturated, unsaturated, branched and linear chains) esterified with fatty alcohols with chain lengths from C8 - C22 (even and uneven numbered, including saturated, unsaturated, branched and linear) in varying proportions to mono-esters.

The available data allows for an accurate hazard and risk assessment of the category and the category concept is applied for the assessment of environmental fate and environmental and human health hazards. Thus, where applicable, environmental and human health effects are predicted from adequate and reliable data for source substance(s) within the group, by interpolation to the target substances in the group (read-across approach), applying the group concept in accordance with Annex XI, Item 1.5, of Regulation (EC) No 1907/2006. In particular, for each specific endpoint the source substance(s) structurally closest to the target substance is/are chosen for read-across, with due regard to the requirements for adequacy and reliability of the available data. Structural similarities and similarities in properties and/or activities of the source and target substance are the basis of read-across.

A detailed justification for the grouping of chemicals and read-across is provided in the technical dossier (see IUCLID Sections 7.1 and 13) and within Chapter 5.1 of the CSR.

 

Overview of skin sensitisation

CAS

Skin Sensitisation

91031-48-0 (b)

Experimental result:

not sensitising

3687-46-5

Experimental result:

not sensitising

59231-34-4 (a)

RA: CAS 3687-46-5, 17673-56-2, 93803-87-3

36078-10-1

RA: CAS 3687-46-5, 17673-56-2, 93803-87-3

95912-86-0

RA: CAS 3687-46-5, 17673-56-2, 93803-87-3

95912-87-1

RA: CAS 3687-46-5, 17673-56-2, 93803-87-3

91031-91-3

RA: CAS 3687-46-5, 17673-56-2, 93803-87-3

85116-88-7

RA: CAS 3687-46-5, 17673-56-2, 93803-87-3

95912-88-2

RA: CAS 3687-46-5, 17673-56-2, 93803-87-3

3234-85-3

RA: CAS 3687-46-5, 17673-56-2, 93803-87-3

22393-85-7

RA: CAS 3687-46-5, 17673-56-2, 93803-87-3

101227-09-2

RA: CAS 3687-46-5, 17673-56-2, 93803-87-3

97404-33-6

RA: CAS 3687-46-5, 17673-56-2, 93803-87-3

72576-80-8

RA: CAS 3687-46-5, 17673-56-2, 93803-87-3

3687-45-4

RA: CAS 3687-46-5, 17673-56-2, 93803-87-3

17673-56-2

Experimental result:

not sensitising

96690-38-9

RA: CAS 3687-46-5, 17673-56-2, 93803-87-3

93803-87-3

Experimental result:

not sensitising

17671-27-1

RA: CAS 3687-46-5, 17673-56-2, 93803-87-3

(a) Category members subject to the REACh Phase-in registration deadline of 31 May 2013 are indicated in bold font.

(b) Substances that are either already registered under REACh or not subject to the REACh Phase-in registration deadline of 31 May 2013 are indicated in normal font.

 

Discussion

Skin sensitisation

CAS 3687-46-5

The skin sensitising potential of decyl oleate (CAS 3687-46-5) was evaluated in a local lymph node assay (LLNA) performed according to OECD 429 (Beerens-Heijnen, 2010). 25 µl of a 25, 50 and 100% suspension of test substance in acetone/olive oil (4:1 v/v) was applied to the dorsal surface of both ears of 5 CBA mice/dose for 3 consecutive days. On Day 6, each animal was injected via the tail vein with 0.25 mL sterile phosphate buffered saline containing 20 µCi of 3H-methyl thymidine. After approximately 5 hours, the mice were sacrificed and the draining lymph nodes of the ears were excised. The nodes were pooled for each animal in PBS and the DNA precipitated with 5% TCA at 4 °C overnight. Slight edema (score 1 of 4) was noted on the ears of 5/5 mice treated with the undiluted substance. This is not considered to have had a significant effect on the activity of the lymph nodes. All the nodes of the animals in the control and treatment groups were normal in size, and no macroscopic abnormalities were noted in the surrounding area. The positive control group (hexyl cinnamic aldehyde) was valid. The mean DPM/animal values for the control, 25, 50 and 100% groups were 488, 571, 951 and 1013, respectively. The SI values calculated for the 25, 50 and 100% groups were 1.2, 2.0 and 2.1, respectively. The SI was lower than 3 up to and including 100%, therefore the test substance is considered to be not skin sensitising. 

A Guinea pig maximisation test was performed with decyl oleate according to the method described by Magnusson & Kligman (Gloxhuber, 1979). 19 female guinea pigs in the test group and 10 females in the control group were induced by epicutaneous exposure to a 1% solution in ethanol, without a dressing. The challenge was performed by open epicutaneous exposure to a 1% formulation in Vaseline. The animals in the treatment group and the control groups did not show any signs of a sensitising effect at the reading time points (24 and 48 h after challenge reaction). This study was considered insufficient for assessment due to the limited data on methods and individual results.

CAS 59231-34-4

The results of a skin sensitisation study performed in rabbits according to a French national guideline (1971) were presented in a publication (Guillot, 1977). During the induction phase, an epicutaneous application of the undiluted test substance or a 15% solution (in 3% polyoxyethylene sorbitan stearate, 80% water, 2% unknown preservative) was repeated daily for 60 days. The epicutaneous challenge was performed with the same concentration on Day 67. No sensitisation was reported. The study was considered insufficient for assessment, as it does not meet important criteria of today’s standard methods.

A skin sensitisation study with tetradecanoic acid, tetradecyl ester (CAS 59231-34-4) was summarised in a review published by the Cosmetic Ingredient Review, (CIR Expert Panel, 1982). The Landsteiner and Jacobs guinea pig sensitisation procedure was followed. No sensitisation was observed. Due to the limited information reported, the results of the studies are considered to be inconclusive.

CAS 95912-86-0

One non-guideline skin sensitisation study was performed with Fatty acids, C8-10, C12-18 alkyl esters (CAS 95912-86-0) (Potokar, 1972). The induction and challenge phases were performed with a 25% solution by intradermal injection; no skin sensitisation was reported. As there was no positive control and very few details from the study protocol were given, the study result was considered to be insufficient for assessment.

In a human skin sensitisation study, 20 volunteers were exposed to the test substance via dermal application (Herzberg, 1968). The inductions were performed daily for 14 consecutive days and the challenge was performed following a 14-day recovery period. No skin sensitisation was reported. The results were considered insufficient for assessment due to the very limited amount of data.

CAS 3234-85-3

In a review publication by the Cosmetic Ingredient Review, two animal studies and a study in human volunteers with tetradecanoic acid, tetradecyl ester (CAS 3234-85-3) were briefly summarised (CIR Expert Panel, 1982). In the animal studies, the Landsteiner and Jacobs guinea pig sensitisation procedure was followed (Landsteiner and Jacobs, 1935). The first study was performed with 10 epicutaneous induction phases and an epicutaneous challenge phase, while the second study was performed with 10 intradermal induction phases and an intradermal challenge phase. Due to the limited information reported, the results of the studies are considered to be inconclusive. An 8% formulation of the test substance (cologne stick) was applied to the skin on one arm of 196 volunteers and covered with an occlusive dressing 3 days a week for a total of 10 induction exposures. After a rest period of 14 days, one challenge application was performed and the skin assessed for sensitisation reactions. No sensitisation reactions were noted.

CAS 17673-56-2

The skin sensitising potential of (Z)-octadec-9-enyl (Z)-docos-13-enoate (CAS 17673-56-2) was evaluated in a Buehler test performed according to a protocol similar to OECD 406 (Pitterman, 1995). The induction treatments were performed on 20 Dunkin Hartley guinea pigs on Day 0, 7 and 14. A 70% solution of the test substance in peanut oil was applied to the shaved skin on the flank of the animals, and covered with an occlusive dressing for 6 hours. On Day 28, all the animals were challenged with a 60% solution of the test substance via topical application on the flank for 6 hours, using an occlusive dressing. 10 guinea pigs in the control group were treated according to the same protocol with the vehicle as the control substance. During the first reading, 1/20 treated animals and 1/10 negative control animals had a positive reaction, respectively. In the second reading, 2/20 treated animals and 1/10 negative control animals had a positive reaction, respectively. The slight, patchy erythema was limited to the left flank, where both the induction and challenge doses were applied. It is possible that the reaction was skin irritation, rather than a sensitisation reaction. All skin irritation effects had cleared within 72 hours after the challenge exposure ended. The result of the reliability check was inconclusive. During the first challenge application with 25% alpha-hexyl cinnamic aldehyde, a sensitisation reaction was induced in 25% (5/20) of the Dunkin Hartley guinea pigs, while the second challenge application did not cause sensitisation reactions. In the negative control group, the first challenge application induced sensitisation in 20% (2/10) of the animals, and the second challenge application did not cause sensitisation reactions. Under the conditions of this study, the test substance is considered to be not skin sensitising.

CAS 93803-87-3

The skin sensitising potential of 2-octyldodecyl isooctadecanoate (CAS 93803-87-3) was evaluated in a Guinea Pig Maximisation Test (GMPT) performed according to a protocol similar to OECD 406 (Busschers, 1998). The first induction (Day 1) was performed on 10 animals by intradermal injection of the undiluted test substance. On Day 7, the animals were treated with 10% sodium lauryl sulphate (SDS) in vaseline, to induce skin irritation. During the second induction on Day 8, the undiluted test substance was applied topically and held in place with a semi-occlusive dressing for 48 hours. On Day 21, all the animals were challenged with the undiluted test substance via topical application under semi-occlusive conditions for 24 hours. 5 guinea pigs in the control group were treated according to the same protocol with the vehicle (corn oil). 48 hours after the intradermal induction, slight to severe erythema was noted at most of the injection sites in the treated and control animals. 4/5 control animals also exhibited necrosis at the FCA/test substance injection site. These effects were caused primarily by the injection and not by a reaction to the test substance. Following the topical induction, severe erythema and scabs were observed at the test site in 3/10 treated animals. No sensitisation was observed in the treated animals during the reading time points 48 and 72 hours after the challenge. The test substance did not cause skin sensitisation under the conditions of the study.

 

Overall conclusion for skin sensitisation

Two Guinea Pig Maximisation Tests and a Local Lymph Node Assay performed with the category members decyl oleate (CAS 3687-46-5), (Z)-octadec-9-enyl (Z)-docos-13-enoate (CAS 17673-56-2) and 2-octyldodecyl isooctadecanoate (CAS 93803-87-3), show that no skin sensitisation was induced and indicate that the remaining category members are not expected to have a skin sensitising potential (Beerens-Heijnen, 2010; Busschers, 1998; Pitterman, 1995).

A detailed reference list is provided in the technical dossier (see IUCLID, section 13) and within the CSR.


Migrated from Short description of key information:
All available studies showed no skin sensitisation potential of the category members.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

According to Article 13 of Regulation (EC) No. 1907/2006 "General Requirements for Generation of Information on Intrinsic Properties of substances", information on intrinsic properties of substances may be generated by means other than tests e.g. from information from structurally related substances (grouping or read-across), provided that conditions set out in Annex XI are met. Annex XI, "General rules for adaptation of this standard testing regime set out in Annexes VII to X” states that “substances whose physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity may be considered as a group, or ‘category’ of substances. This avoids the need to test every substance for every endpoint". Since the group concept is applied to the members of the LCAE category, data will be generated from data for reference source substance(s) to avoid unnecessary animal testing. Additionally, once the group concept is applied, substances will be classified and labelled on this basis.

Therefore, based on the group concept, the available data on skin sensitisation do not meet the classification criteria according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.