Registration Dossier

Administrative data

Description of key information

Skin, single exposure patch test, human: not irritating
Eye, Draize testing method, rabbit: not irritating

Key value for chemical safety assessment

Skin irritation / corrosion

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

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
Basic data given (comparable to guidelines/standards). Limited data on materials and method, test substance purity not specified.
Principles of method if other than guideline:
Draize Testing method (Draize JH et al., J. Pharm. Exp. Ther. 82: 377-390, 1944) as prescribed by the FDA (in The Federal Register 38 No.187 §15000.42, USA).
GLP compliance:
no
Species:
rabbit
Strain:
not specified
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Summit View Farm, Belvedere, USA
- Weight at study initiation: 1.8 - 2.4 kg
- Diet: Wayne animal feed, ad libitum
- Water: ad libitum
- Acclimation period: yes, unreported time period
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
Duration of treatment / exposure:
single application without washing
Observation period (in vivo):
7 days
Reading time points: 24, 48 and 72 h and 7 days
Number of animals or in vitro replicates:
6 (males and females)
Details on study design:
SCORING SYSTEM: Draize scoring system

TOOL USED TO ASSESS SCORE: hand-held lens
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: mean after 24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility: not applicable
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility: not applicable
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility: not applicable
Irritation parameter:
cornea opacity score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility: not applicable
Irritation parameter:
cornea opacity score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility: not applicable
Irritation parameter:
cornea opacity score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility: not applicable
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: reversibility: not applicable
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: reversibility: not applicable
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: reversibility: not applicable
Irritation parameter:
iris score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: reversibility: not applicable
Irritation parameter:
iris score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: reversibility: not applicable
Irritation parameter:
iris score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: reversibility: not applicable
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
3
Reversibility:
other: reversibility: not applicable
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
3
Reversibility:
other: reversibility: not applicable
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
3
Reversibility:
other: reversibility: not applicable
Irritation parameter:
conjunctivae score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
3
Reversibility:
other: reversibility: not applicable
Irritation parameter:
conjunctivae score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
3
Reversibility:
other: reversibility: not applicable
Irritation parameter:
conjunctivae score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
3
Reversibility:
other: reversibility: not applicable
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility: not applicable
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility: not applicable
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility: not applicable
Irritation parameter:
chemosis score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility: not applicable
Irritation parameter:
chemosis score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility: not applicable
Irritation parameter:
chemosis score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility: not applicable
Irritant / corrosive response data:
No eye irritation effect of any kind was observed in any animals at any reading time point. All the scores were 0.
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for read-across

In vitro data on the eye irritation potential of Isohexadecyl 12 -[(1 -oxooctadecyl)oxy]octadecanoate (CAS 97338-28-8) is available, but does not meet the data requirements. The assessment was therefore based on the available in vitro data on the test substance and on an in vivo study conducted with an analogue substance as part of a read across approach, which is in accordance with Regulation (EC) No. 1907/2006, Annex XI, 1.5. 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 of 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 analogue read-across approach is provided in the technical dossier (see IUCLID Section 13).

Skin irritation

Human data

CAS 97338-28-8

The skin irritation potential of Isohexadecyl 12 -[(1 -oxooctadecyl)oxy]octadecanoate was assessed in a single exposure patch test, performed with 12 human volunteers (1 male, 13 females) (key, 2001). A further 2 volunteers were excluded from the study due to skin irritation at the negative control site and no reaction to the positive control, respectively. In the first step, the undiluted test substance was applied to the skin of 3 volunteers for 1, 4, 8 and 24 h. As no severe irritating reactions were observed, in the second step the undiluted substance was applied to the upper back of a further 11 subjects for 24 h. The test substance was applied in a Finn Chamber under occlusive conditions. A positive control containing 1% solution of sodium sulfate and a negative control containing distilled water was applied in parallel with the test cup. The skin irritation effects (erythema, edema, vesicles, cutaneous dryness, wrinkling, glazing) were assessed 30-60 min and 24 h after patch removal and the subjective experience of the volunteers was recorded. The test material did not induce skin sensitisation in any of the 12 subjects. 

Eye irritation

In vitro data

CAS 97338-28-8

Two non-guideline in vitro studies were performed to assess the eye corrosion effects of Isohexadecyl 12-[(1-oxooctadecyl)oxy]octadecanoate.

The first test was a cytotoxicity assay in which fibroblasts from rabbit cornea (SIRC cell line) were exposed to Isohexadecyl 12-[(1-oxooctadecyl)oxy]octadecanoate (in vitro cytotoxicity, 2001). The fibroblasts were pre-incubated in culture plate wells for 48 h at 37 °C, and then transferred to a second plate containing the undiluted test substance. The cells were incubated for 30 min, 1 and 4 h at 37 °C with the test substance. Culture medium treated cells served as negative control. Using the MTT test, the cell viability was determined by incubating the cells in MTT solution for 2 -3 h prior to measuring the absorption at 570 nm. The cytotoxicity was 4, 21 and 38% relative to the control (100%), for 30 min, 1 and 4 h exposure, respectively. Based on the results, an ocular irritation index of 7.4 was calculated, indicating a slight irritation potential.

In the second test, the Hen's Egg Test-Chorioallantoic Membrane (HET-CAM) assay was applied according to a protocol endorsed by ICCVAM (HET-CAM, 2001). The potential of the test substance to cause (severe) ocular irritancy was measured by its ability to induce toxicity in the chorioallantoic membrane (CAM) of a chicken egg. Fertilised chicken eggs were incubated for 10 days (rotating to avoid the membrane attaching to the shell) and the CAM was exposed by removing part of the shell and the inner egg membrane. 0.3 mL undiluted Isohexadecyl 12-[(1-oxooctadecyl)oxy]octadecanoate as applied to the CAM of 4 eggs for 20 seconds before rinsing the membrane with 5 mL saline (at 37 °C). The effects were measured by scoring the occurrence and intensity of haemorrhage, coagulation and vessel lysis (hyperaemia). 0.9% NaCl was used as the negative control, and 3% sodium lauryl sulfate was used as the positive control. The score was used to classify the irritancy level of the test substance, with a maximum score of 21 indicating a corrosive effect. Hyperaemia score 1 (of 5) was noted in 2/4 eggs, adding up to an irritation index (IP-CAM) of 0.5, indicating the test substance is ‘not irritating’ according to the scoring system. The positive control IP-CAM was 11.25.

As the SIRC cell line and HET-CAM methods are non-validated test systems, the results of both tests are inadequate for classification purposes. Therefore, data available for the analogue substance CAS 90052-75-8 is included in the dossier.

In vivo data

CAS 90052-75-8

An acute eye irritation study was performed with 2-octyldodecyl 12-[(1-oxooctadecyl)oxy]octadecanoate according to the Draize testing method (Draize JH et al., J. Pharm. Exp. Ther. 82: 377-390, 1944) as prescribed by the FDA (in The Federal Register 38 No.187 §15000.42, USA) (key, 1978). 0.1 mL of the test substance was instilled into the eyes of 6 rabbits. The animals were observed for 7 days and scoring was performed 24, 48 and 72 h, and 7 days after instillation.

No eye irritation effects of any kind (conjunctivitis, chemosis, and effects on the iris or cornea) were observed in any animal at any reading time point. All the scores were 0. The test substance is not considered to be irritating to the eye.

Overall conclusion for skin and eye irritation

The available data on the target and source substances did not indicate skin or eye irritating properties. Therefore, the target substance Isohexadecyl 12-[(1-oxooctadecyl)oxy]octadecanoate is not a skin irritant and not expected to be an eye irritant.


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 analogue concept is applied to Isohexadecyl 12-[(1-oxooctadecyl)oxy]octadecanoate (CAS 97338-28-8) data will be generated from data for reference source substance(s) to avoid unnecessary animal testing. Additionally, once the analogue read-across concept is applied, substances will be classified and labelled on this basis.

Therefore, based on data available for the target and analogue substances, the available data on skin and eye irritation do not meet the classification criteria according to Regulation (EC) 1272/2008, and are therefore conclusive but not sufficient for classification.