Isopentyl oleate

Endpoint summary

Description of key information

Skin irritation (WoE, OECD 404), rabbit: not irritating (RA CAS 163961-32-8 and RA CAS 34316-64-8)
Eye irritation (WoE, OECD 405), rabbit: not irritating (RA CAS 163961-32-8 and RA CAS 142-91-6)

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

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 only limited data available on skin and eye irritation of isopentyl oleate (CAS 627-89-4). In order to fulfil the standard information requirements set out in Annex VII and VIII, 8.1. and 8.2., in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006, read-across from structurally related substances was 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 substances may be predicted as similar provided that their physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity.

Overview of skin and eye irritation

CAS	Chemical name	Molecular weight [g/mol]	Skin irritation	Eye irritation
627-89-4 (a)	Isopentyl oleate	326.56 - 354.61	WoE: RA: CAS 163961-32-8 RA: CAS 34316-64-8	WoE: RA: CAS 163961-32-8 RA: CAS 142-91-6
163961-32-8 (b)	Fatty acids, C16-18 and C18 unsatd. branched and linear, butyl esters	312.53 - 340.58	Experimental result: not irritating	Experimental result: not irritating
34316-64-8 (b)	Dodecanoic acid, hexyl ester	284.49	Experimental result: not irritating	--
142-91-6 (b)	Isopropyl palmitate	298.51	Experimental result: not irritating	Experimental result: not irritating

(a) The substance subject to registration is indicated in bold font.

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

The above mentioned substances are considered to be similar on the basis of the structural similar properties and/or activities. The available endpoint information is used to predict the same endpoints for isopentyl oleate (CAS 627-89-4). A detailed analogue approach justification is provided in the technical dossier (see IUCLID Section 13).

 

Discussion

No data on skin and eye irritation is available with isopentyl oleate (CAS 627-89-4). Therefore, read across from the structurally analogue substances fatty acids, C16-18 and C18 unsatd. branched and linear, butyl esters (CAS 163961-32-8), dodecanoic acid, hexyl ester (CAS 34316-64-8) and isopropyl palmitate (CAS 142-91-6) was applied.

 

Skin irritation

CAS 163961-32-8

In the reliable skin irritation study performed according to OECD TG 404 three male New Zealand White rabbits were exposed to 0.5 mL of the neat test material (CAS 163961-32-8) for 4 hours applied onto the shaved skin via semi-occlusive dressing (Sanders, 2002a). Skin reactions were evaluated according to the Draize scoring system 1, 24, 48 and 72 hours post-application. No symptoms of systemic toxicity were observed in any animal during the test period and no mortality occurred during the course of the study. Well-defined erythema and edema formation (grade 2) was observed in 3/3 animals one hour after patch removal regressing to slight erythema and edema (grade 1) in 3/3 animals 24 hours after patch removal. Edema formation was fully reversible in 3/3 animals within 48 hours, whereas slight erythema (grade 1) were still present in 2/3 animals after 48 hours after patch removal, but being fully reversible within 72 hours after patch removal. The mean values for erythema and edema were calculated to be 0.56 and 0.33, respectively.

 

CAS 34316-64-8

In the reliable skin irritation study performed equivalent or similar to OECD TG 404 six male New Zealand rabbits were exposed to 0.5 mL of the neat test material (CAS 34316-64-8) for 24 hours applied onto the intact and incised skin via occlusive dressing (Masson, 1987). Skin reactions were evaluated according to the Draize scoring system 24 and 72 hours post-application. Slight (3/6 animals, grade 1) and well-defined (3/6 animals, grade 2) erythema formation was recorded 24 hours after patch removal (intact skin). Similar observations were identified in animals with incised skin (4/6 animals, grade 2: 2/6 animals, grade 1). Slight edema formation (grade 1) was only recorded in 1/6 animals with intact as well as incised skin. Slight and well-defined erythema were still present in 4/6 and 1/6 animals (intact skin) and 3/6 and 1/6 animals (incised skin) 72 hours after patch removal, respectively. Slight edema was recorded in 1/6 animals at this reading time point (intact and incised skin). The mean values for erythema were calculated to be 1.33 (intact skin) and 1.39 (incised skin), respectively. The mean values for edema were calculated to be 0.17 for both intact skin and incised skin, respectively.

Taken together, the available data on skin irritation from structural analogue substances do only indicate mild irritating potential. Therefore, according to EU classification criteria, the target substance isopentyl oleate (CAS 627-89-4) is not to be classified.

 

Eye irritation

CAS 163961-32-8

In the reliable eye irritation study with fatty acids, C16-18 and C18 unsatd. branched and linear, butyl esters (CAS 163961-32-8) performed according to OECD TG 405 (Sanders, 2002b) 0.1 mL of the neat test material was instilled in the eye of three male New Zealand White rabbits. The eyes were examined and the changes were graded according to the Draize scoring system 1, 24, 48 and 72 hours post-application. No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred during the course of the study. Neither iridial irritation nor corneal opacity was observed in any animal during the course of the study. Chemosis (grade 1) was recorded in 3/3 animals 1 hour post-application but was fully reversible in all animals within 24 hours. Minimal to moderate conjunctival irritation (grade 1-2) was noted in 3/3 animals 1 hour after treatment with minimal conjunctival irritation (grade 1) in 2/3 animals at the 24-hour observation time point. All effects were fully reversible within 48 hours post-application of the test material. The mean value for conjunctival irritation was calculated to be 0.22.

 

CAS 142-91-6

In the reliable eye irritation study with isopropyl palmitate (CAS 142-91-6) performed equivalent or similar to OECD TG 405 (Prince, 1971) 0.1 mL of the neat test material was instilled in the eye of six rabbits of unknown strain and gender. The eyes were examined and the changes were graded according to the Draize scoring system 1, 24, 48 and 72 hours post-application. No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred during the course of the study. Neither iridial irritation nor corneal opacity was observed in any animal during the course of the study. Minimal conjunctival irritation (grade 1) was noted in 5/6 animals 1 hour post-application and was still present in 3/6 animals 24 and 48 hours post-application but fully reversible in all animals within 72 hours post-application. Chemosis (grade 1) was recorded in 3/6 animals 1 hour and in 1/6 animals 24 hours post-application. These effects were fully reversible within 48 hours in all animals. The mean values for conjunctival irritation and chemosis were calculated to be 0.33 and 0.06, respectively.

 

Taken together, the available data on eye irritation from structural analogue substances do only indicate mild irritating potential. Therefore, according to EU classification criteria, the target substance isopentyl oleate (CAS 627-89-4) is not to be classified.

Justification for selection of skin irritation / corrosion endpoint:
Hazard assessment is conducted by means of read-across from structural analogues. All available studies are adequate and reliable based on the identified similarities in structure and intrinsic properties between source and target substances and overall quality assessment.

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

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 isopentyl oleate (CAS 627-89-4), 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 the analogue read-across approach, 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.