2-octyldodecyl 12-[(1-oxooctadecyl)oxy]octadecanoate

Endpoint summary

Description of key information

Skin (in vivo, Draize testing method; human single patch test): not irritating

Eye (in vivo, Draize testing method), rabbit: not irritating

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

27 Mar - 7 Apr 1978

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, no experimental 48 h reading performed, occlusive exposure, 24-hour exposure period, 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; Draize JH, Assoc. Food Drugs Officials of the United States: 46-49, Topeka Kansas, 1965) as described by the FDA (in The Federal Register 38 No.187 §15000.41, USA).

GLP compliance:

no

Species:

rabbit

Strain:

not specified

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Summit View Farm, Belvedere, USA
- Diet: Wayne animal feed, ad libitum
- Water: ad libitum
- Acclimation period: yes, unreported time period

Type of coverage:

occlusive

Preparation of test site:

other: shaved and abraded

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL

Duration of treatment / exposure:

24 h

Observation period:

72 h
Reading time points: 24 and 72 h

Number of animals:

6

Details on study design:

TEST SITE
- Area of exposure: 2.5 x 2.5 cm
- Type of wrap if used: The treated skin was covered with an occlusive patch held in place with adhesive tape. The trunk of the animals were wrapped with occlusive wrapping and the animals immobilised.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Residual test material was removed, no further information was given
- Time after start of exposure: 24 h

SCORING SYSTEM: Draize scoring system

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.33

Max. score:

4

Reversibility:

fully reversible within: 72 h

Remarks on result:

other: No 48 h data are available; for calculation of mean scores, the 48 h values were assumed to be the same as those at 24 h (worst case assumption: persistence of effects seen at 24 h over 48 h). Only the data on intact skin was considered for evaluation.

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Remarks on result:

other: No 48 h data are available; for calculation of mean scores, the 48 h values were assumed to be the same as those at 24 h (worst case assumption: persistence of effects seen at 24 h over 48 h). Only the data on intact skin was considered for evaluation.

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Remarks on result:

other: No 48 h data are available; for calculation of mean scores, the 48 h values were assumed to be the same as those at 24 h (worst case assumption: persistence of effects seen at 24 h over 48 h). Only the data on intact skin was considered for evaluation.

Irritation parameter:

erythema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Remarks on result:

other: No 48 h data are available; for calculation of mean scores, the 48 h values were assumed to be the same as those at 24 h (worst case assumption: persistence of effects seen at 24 h over 48 h). Only the data on intact skin was considered for evaluation.

Irritation parameter:

erythema score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

not fully reversible within: 72 h

Remarks on result:

other: No 48 h data are available; for calculation of mean scores, the 48 h values were assumed to be the same as those at 24 h (worst case assumption: persistence of effects seen at 24 h over 48 h). Only the data on intact skin was considered for evaluation.

Irritation parameter:

erythema score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Remarks on result:

other: No 48 h data are available; for calculation of mean scores, the 48 h values were assumed to be the same as those at 24 h (worst case assumption: persistence of effects seen at 24 h over 48 h). Only the data on intact skin was considered for evaluation.

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 72 h

Remarks on result:

other: No 48 h data are available; for calculation of mean scores, the 48 h values were assumed to be the same as those at 24 h (worst case assumption: persistence of effects seen at 24 h over 48 h). Only the data on intact skin was considered for evaluation.

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Remarks on result:

other: No 48 h data are available; for calculation of mean scores, the 48 h values were assumed to be the same as those at 24 h (worst case assumption: persistence of effects seen at 24 h over 48 h). Only the data on intact skin was considered for evaluation.

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Remarks on result:

other: No 48 h data are available; for calculation of mean scores, the 48 h values were assumed to be the same as those at 24 h (worst case assumption: persistence of effects seen at 24 h over 48 h). Only the data on intact skin was considered for evaluation.

Irritation parameter:

edema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Remarks on result:

other: No 48 h data are available; for calculation of mean scores, the 48 h values were assumed to be the same as those at 24 h (worst case assumption: persistence of effects seen at 24 h over 48 h). Only the data on intact skin was considered for evaluation.

Irritation parameter:

edema score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Remarks on result:

other: No 48 h data are available; for calculation of mean scores, the 48 h values were assumed to be the same as those at 24 h (worst case assumption: persistence of effects seen at 24 h over 48 h). Only the data on intact skin was considered for evaluation.

Irritation parameter:

edema score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Remarks on result:

other: No 48 h data are available; for calculation of mean scores, the 48 h values were assumed to be the same as those at 24 h (worst case assumption: persistence of effects seen at 24 h over 48 h). Only the data on intact skin was considered for evaluation.

Irritant / corrosive response data:

Intact skin:
At the 24-h reading time point, 1/6 rabbits had well defined erythema (score 2) and very slight edema (score 1), which had cleared completely within 72 h. 1/6 rabbits with no skin irritation effects at the 24-h reading time point had very slight erythema at the 72-h reading time point.

Abraded skin:
1/6 rabbits had well defined erythema (score 2) and slight edema (score 2) at the 24-h reading time point. The erythema was reduced in severity (score 1) at the 72-h reading time point, while the edema had cleared completely. Only the data on intact skin was considered for evaluation.

Table 1. Results of skin irritation study

Observation time	Rabbit no.
	1		2		3		4		5		6
	Erythema	Edema	Erythema	Edema	Erythema	Edema	Erythema	Edema	Erythema	Edema	Erythema	Edema
24 h	2	1	0	0	0	0	0	0	0	0	0	0
48 h	No experimental data available; for calculation of mean scores, the 48 h values were assumed to be the same as those at 24 h (worst case assumption)
72 h	0	0	0	0	0	0	0	0	1	0	0	0

 

Table 2. Calculation of mean scores

	Rabbit no.
	1		2		3		4		5		6
	Erythema	Edema	Erythema	Edema	Erythema	Edema	Erythema	Edema	Erythema	Edema	Erythema	Edema
Mean value 24 + 48 + 72 h*	1.33	0.67	0	0	0	0	0	0	0.33	0	0	0

 

*No 48 h data are available: for calculation of mean scores, the 48 h values were assumed to be the same as those at 24 h (worst case assumption: persistence of effects seen at 24 h over 48 h).

Interpretation of results:

study cannot be used for classification

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:

key study

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:

mean

Remarks:

of 6 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Irritation parameter:

iris score

Basis:

mean

Remarks:

of 6 animals

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: reversibility: not applicable

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

of 6 animals

Time point:

24/48/72 h

Score:

0

Max. score:

3

Reversibility:

other: reversibility: not applicable

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

of 6 animals

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.

Conclusions:

CLP: not classified

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 vivo data on the skin and eye irritation/corrosion potential of 2-octyldodecyl 12-[(1-oxooctadecyl)oxy]octadecanoate (CAS 90052-75-8) is available, although the skin irritation/corrosion data is not sufficient for classification purposes. In addition, read across was applied from the source substance Isohexadecyl 12-[(1-oxooctadecyl)oxy]octadecanoate (CAS 97338-28-8). The assessment was therefore based on the available in vivo data on the test substance and on 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

CAS 90052-75-8

A study assessing the skin irritation potential of 2-octyldodecyl 12-[(1-oxooctadecyl)oxy]octadecanoate was performed according to the Draize Testing method as described by the FDA (in The Federal Register 38 No.187 §15000.41, USA) and described in a study report with few details (key study, 1978). 0.5 mL of the test substance was applied for 24 hours to the shaved and abraded skin of 6 rabbits under occlusive conditions. The untreated skin site of the animals served as the control. The skin reactions (erythema and oedema) were scored 24 and 72 hours after patch removal. As no reading was performed 48 hours after patch removal, the mean scores were calculated by assuming the 48 hrs values were the same as those at 24 hours, making a worst-case assumption. For intact skin, 1/6 rabbits had well defined erythema (score 2) and very slight edema (score 1) at the 24-h reading time point, which had cleared completely within 72 h. 1/6 rabbits with no skin irritation effects at the 24-h reading time point had very slight erythema at the 72-h reading time point. The individual mean erythema scores over the 24 and 72 hours reading time points (intact skin) were 1.33, 0, 0, 0, 0.33 and 0; the edema scores were 0.67, 0, 0, 0, 0 and 0. The results obtained on abraded skin were not considered for hazard assessment. 1/6 animals showed very slight erythema (score 1) at the final reading time point, which means it is not clear if the skin effect was reversible or not. However, as all effects had cleared within 72 h (1/6 rabbits) or no effects were seen at all (4/6 animals), it is very likely that the effects would be reversible within 21 days. The substance is most likely not irritating under the conditions of the study, but the results cannot be used for classification purposes.

CAS 97338-28-8

The skin irritation potential ofIsohexadecyl 12-[(1-oxooctadecyl)oxy]octadecanoatewas assessed in a single exposure patch test, performed with 14 human volunteers (1 male, 13 females) (key study, 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 irritation 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 (supporting study 1, 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 (supporting study 2, 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. 

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 study, 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 2-octyldodecyl 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 2-octyldodecyl 12-[(1-oxooctadecyl)oxy]octadecanoate (CAS 90052-75-8) 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.