Isopentyl oleate

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route

Endpoint conclusion:

no study available

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Effects on developmental toxicity

Description of key information

Developmental toxicity/teratogenicity (OECD 414, oral), rat: NOAEL (maternal/embryonal) = 1000 mg/kg bw/day (RA CAS 91031-48-0 and RA CAS 22047-49-0)

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

1 000 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

The available information comprises adequate, reliable (Klimisch score 2) and consistent 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. The selected study is thus sufficient to fulfil the standard information requirements set out in Annex VIII-IX, 8.7, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Additional information

Justification for grouping of substances and read-across

There are only limited data available on toxicity to reproduction of isopentyl oleate (CAS 627-89-4). In order to fulfil the standard information requirements set out in Annex VIII, 8.7, 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 toxicity to reproduction

CAS	Chemical name	Molecular weight [g/mol]	Toxicity to reproduction	Developmental toxicity/teratogenicity
627-89-4 (a)	Isopentyl oleate	326.56 - 354.61	--	RA: CAS 91031-48-0 RA: CAS 22047-49-0
91031-48-0 (b)	Fatty acids, C16-18, 2-ethylhexyl esters	368.65-396.7	--	Experimental result: NOAEL (maternal/embryonal) =1000 mg/kg bw/day (rat)
22047-49-0 (b)	2-ethylhexyl stearate	396.7	--	Experimental result: NOAEL (maternal/embryonal) =1000 mg/kg bw/day (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 substance is 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 toxicity to reproduction is available with isopentyl oleate (CAS 627-89-4). Therefore, read across from the structurally analogue substances fatty acids, C16-18, 2-ethylhexyl esters (CAS 91031-48-0) and 2-ethylhexyl stearate (CAS 22047-49-0) was applied.

Toxicity to reproduction (fertility)

According to Regulation (EC) No 1907/2006, Annex VIII, 8.7.1., column 2, a screening test for toxicity to reproduction is not required as two tests for prenatal developmental toxicity (Annex IX, 8.7.2) are available for the structural related substances fatty acids, C16-18, 2-ethylhexyl esters (CAS 91031-48-0) and 2-ethylhexyl stearate (CAS 22047-49-0), which will be used for read-across. On the basis of these prenatal developmental toxicity studies no test item related toxicological findings in dams or fetuses were revealed.

 

Developmental toxicity/teratogenicity

CAS 91031-48-0

A Prenatal Developmental Toxicity Study was performed with fatty acids, C16-18, 2-ethylhexyl esters (CAS 91031-48-0) according to OECD TG 414 (Pittermann, 1994). Groups of 24 female Sprague-Dawley rats received daily oral gavage doses of the test substance in arachis oil at dose levels of 0, 100, 300 and 1000 mg/kg bw/day during gestational days 6 to 15. On day 20 of gestation the animals were euthanized and examined for maternal and fetal parameters. Based on the number of implantations, number of total litter losses by resorption, mortality, clinical signs, body weight, gross pathology and organ weights of maternal animals the NOAEL for maternal toxicity was found to be 1000 mg/kg bw/day. Examination of fetus litter size and weights, offspring viability (number alive and number dead), sex ratio, grossly visible abnormalities, external, head, soft tissue and skeletal abnormalities showed no differences to control and no indication for teratogenic effects. Therefore, the NOAEL for embryo-/fetotoxicity and teratogenicity in rats for fatty acids C16-18, 2-ethylhexyl esters was found to be 1000 mg/kg bw/day.

 

CAS 22047-49-0

The developmental toxicity of 2-ethylhexyl stearate (CAS 22047-49-0) was investigated according to OECD TG 414 and GLP conditions (Aulmann, 2000). Groups of 24 female Sprague-Dawley rats received daily oral gavage doses of the test substance in arachis oil at dose levels of 0, 100, 300 and 1000 mg/kg bw/d during gestational days 6 to 15. On day 20 of gestation the animals were euthanized and examined for maternal and fetal parameters. Based on the number of implantations, number of total litter losses by resorption, mortality, clinical signs, body weight, gross pathology and organ weights of maternal animals the NOAEL for maternal toxicity was found to be 1000 mg/kg bw/d. Examination of fetus litter size and weights, offspring viability (number alive and number dead), sex ratio, grossly visible abnormalities, external, head, soft tissue and skeletal abnormalities showed no differences to control and no indication for teratogenic effects. Therefore, the NOAEL for embryo-/fetotoxicity and teratogenicity in rats for 2-ethylhexyl stearate was found to be 1000 mg/kg bw/day.

Taken together, the available data on toxicity to reproduction from structural analogue substances do not indicate any toxicological adverse effect on maternal and embryonal toxicity. Therefore, according to EU classification criteria, the target substance isopentyl oleate (CAS 627-89-4) is not to be classified.

Justification for selection of Effect on developmental toxicity: via oral route:
Hazard assessment is conducted by means of read-across from structural analogues. The selected study is the most adequate and reliable study based on the identified similarities in structure and intrinsic properties between source and target substance and overall assessment of quality, duration and dose.

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 toxicity to reproduction do not meet the classification criteria according to Regulation (EC) 1272/2008, and are therefore conclusive but not sufficient for classification.