Isopentyl oleate

Endpoint summary

Description of key information

Oral (WoE): LD50 (OECD 401), rat >2000 mg/kg bw (RA CAS 84988-79-4); LD50 (OECD 423), rat >2000 mg/kg bw (RA CAS 112-11-8)
Inhalation (WoE): LC50 (OECD 436), rat >5.7 mg/L air (RA CAS 26399-02-0); LC50 (OECD 436), rat >5.3 mg/L air (RA CAS 67762-63-4)
Dermal LD50 (OECD 402), rat >2000 mg/kg bw (RA CAS 163961-32-8)

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The available information comprises adequate, reliable (Klimisch score 2) studies from reference substances with similar structure and intrinsic properties. Read-across is justified based on common origin, common precursors and breakdown products of hydrolysis and consistent trends in the toxicological profile. Taken together, the information from these independent sources is consistent and provides sufficient weight of evidence for hazard assessment leading to an endpoint conclusion in accordance with Annex XI, 1.2, of Regulation (EC) No 1907/2006. Therefore, the available information as a whole is sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The available information comprises adequate, reliable (Klimisch score 2 due to read-across) studies from reference substances with similar structure and intrinsic properties. Read-across is justified based on common origin, common precursors and breakdown products of hydrolysis and consistent trends in the toxicological profile.

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The available information comprises adequate, reliable (Klimisch score 2) studies from reference substances with similar structure and intrinsic properties. Read-across is justified based on common origin, common precursors and breakdown products of hydrolysis and consistent trends in the toxicological profile.

Additional information

Justification for grouping of substances and read-across

There are only limited data available on acute toxicity of isopentyl oleate (CAS 627-89-4). In order to fulfil the standard information requirements set out in Annex VII and VIII, 8.5, 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 acute toxicity

CAS	Chemical name	Molecular weight [g/mol]	Acute toxicity Oral	Acute toxicity Inhalation	Acute toxicity Dermal
627-89-4 (a)	Isopentyl oleate	326.56 - 354.61	WoE: RA: CAS 112-11-8 RA: CAS 84988-79-4	WoE: RA: CAS 26399-02-0 RA: CAS 67762-63-4	RA: CAS 163961-32-8
112-11-8 (b)	Isopropyl oleate	324.55	Experimental result: LD50 >2000 mg/kg bw (rat)	--	--
84988-79-4 (b)	Fatty acids, C16-18 and C18-unsatd., butyl esters	312.53 - 340.58	Experimental result: LD50 >2000 mg/kg bw (rat)	--	--
26399-02-0 (b)	2-ethylhexyl oleate	394.67	Experimental result: LD50 >5000 mg/kg bw (mouse)	Experimental result: LC50 > 5.7 mg/L air (rat)	--
67762-63-4 (b)	Fatty acids, tail-oil, butyl esters	338.57 - 336.56	--	Experimental result: LC50 > 5.3 mg/L air (rat)	--
163961-32-8 (b)	Fatty acids, C16-18 and C18 unsatd. branched and linear, butyl esters	312.53-340.58	Experimental result: LD50 >2000 mg/kg bw (rat)	--	Experimental result: LD50 >2000 mg/kg bw (rat)

(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 acute toxicity is available with isopentyl oleate (CAS 627-89-4). Therefore, read across from the structurally analogue substances isopropyl oleate (CAS 112-11-8), Fatty acids, C16-18 and C18-unsatd., butyl esters (CAS 84988-79-4), 2-ethylhexyl oleate (CAS 26399-02-0), Fatty acids, tail-oil, butyl esters (CAS 67762-63-4) and Fatty acids, C16-18 and C18 unsatd. branched and linear, butyl esters (CAS 163961-32-8) was applied.

 

Acute oral toxicity

CAS 112-11-8

A reliable acute oral toxicity study with isopropyl oleate (CAS 112-11-8) is available and was performed according to OECD TG 423 and in compliance with GLP (Rijcken, 1997). In this limit test three fasted Wistar rats of each sex were administered a single dose of 2000 mg/kg bw of the test substance (CAS 112-11-8) via oral gavage. The animals were observed for 14 days after administration. No mortalities occurred during the entire study period. Two hours after dosing hunched posture and uncoordinated movements were noted in two females. No clinical signs of toxicity were recorded in any animal during the remaining study period. There were no remarkable changes or differences in body weights during the study period. Gross pathology revealed no abnormalities at necropsy. Thus, the acute oral LD50 value for males/females was calculated to be greater than 2000 mg/kg bw.

CAS 84988-79-4

A reliable acute oral toxicity study with Fatty acids, C16-18 and C18-unsatd., isobutyl esters (CAS 84988-79-4) is available and was performed equivalent or similar to OECD TG 401 (Potokar, 1986). In this limit test two fasted Wistar rats of each sex were administered a single dose of 2000 mg/kg bw of the test substance (CAS 84988-79-4) via oral gavage. The animals were observed for 15 days after administration. No mortalities occurred and no signs of systemic toxicity were recorded during the entire study period. Slight piloerection was limited to 1 - 2.5 hours after application of the test material. There were no remarkable changes or differences in body weights during the study period. Gross pathology revealed no abnormalities at necropsy. The acute oral LD50 value for males/females was calculated to be greater than 2000 mg/kg bw.

Taken together, the available data on acute oral toxicity from structural analogue substances do not indicate any relevant systemic toxicity. Therefore, according to EU classification criteria, the target substance isopentyl oleate (CAS 627-89-4) is not to be classified.

 

Acute inhalation toxicity

CAS 26399-02-0

A reliable acute inhalation toxicity study was performed with 2-ethylhexyl oleate (CAS 26399-02-0) according to OECD TG 436 and in compliance with GLP (Huygevoort, 2010a). In this study following the acute toxic class method three Crl:WI(Han) rats of each sex were exposed to an aerosol with an analytical concentration of 5.7 ± 0.4 mg/L of the test substance (CAS 26399-02-0) for 4 hours in an nose-only inhalation exposure chamber. No mortalities were reported during the exposure or within the 14 days observation period. Clinical signs were not eveident during exposure but hunched posture was shown by all animals on Day 2 after exposure. Additionally, body weight gain in males and females was within the range expected for rats of this strain and age used in this type of study and no abnormalities were found at macroscopic post mortem examination of the animals. Therefore, the acute inhalation LC50 value was calculated to be greater than 5.7 mg/L.

 

CAS 67762-63-4

A reliable acute dermal toxicity study was performed with fatty acids, C16-18 and C18 unsatd. branched and linear, butyl esters (CAS 163961-32-8) according to OECD TG 402 and in compliance with GLP (Sanders, 2004). In this limit test five Sprague-Dawley rats of each sex were exposed to a single dose of 2000 mg/kg bw of the test substance (CAS 163961-32-8) for 24 h via semi-occlusive dressing and observed for 14 days post-application. No mortalities occurred during the entire study period. No signs of systemic toxicity and no dermal irritation were observed up to the end of the observation period. Body weight gain was normal except for one female which showed a body weight loss in the first week but expected body weight gain during the second week. No abnormalities were detected at necropsy at the end of the 14-day observation period. The acute dermal LD50 value was calculated to be greater than 2000 mg/kg bw.

Taken together, the available data on acute inhalation toxicity from structural analogue substances do not indicate any systemic toxicity. Therefore, according to EU classification criteria, the target substance isopentyl oleate (CAS 627-89-4) is not to be classified. 

 

Acute dermal toxicity

CAS 163961-32-8

A reliable acute dermal toxicity study was performed with fatty acids, C16-18 and C18 unsatd. branched and linear, butyl esters (CAS 163961-32-8) according to OECD TG 402 and in compliance with GLP (Sanders, 2004). In this limit test five Sprague-Dawley rats of each sex were exposed to a single dose of 2000 mg/kg bw of the test substance (CAS 163961-32-8) for 24 h via semi-occlusive dressing and observed for 14 days post-application. No mortalities occurred during the entire study period. No signs of systemic toxicity and no dermal irritation were observed up to the end of the observation period. Body weight gain was normal except for one female which showed a body weight loss in the first week but expected body weight gain during the second week. No abnormalities were detected at necropsy at the end of the 14-day observation period. The acute dermal LD50 value was calculated to be greater than 2000 mg/kg bw.

Therefore, according to EU classification criteria, the target substance isopentyl oleate (CAS 627-89-4) is not to be classified.

Justification for selection of acute toxicity – oral 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 acute toxicity – inhalation 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 acute toxicity – dermal 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 acute toxicity do not meet the classification criteria according to Regulation (EC) 1272/2008, and are therefore conclusive but not sufficient for classification.