Isopentyl oleate

Endpoint summary

Description of key information

Repeated dose toxicity, oral (OECD 407), rat: NOAEL =1000 mg/kg bw/day (RA CAS 110-27-0) 

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

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 an adequate and reliable study (Klimisch score 2) from a reference substance 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, 8.6, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Justification for grouping of substances and read-across

There are only limited data available on repeated dose toxicity of isopentyl oleate (CAS 627-89-4). In order to fulfil the standard information requirements set out in Annex VIII, 8.6, 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 repeated dose toxicity

CAS	Chemical name	Molecular weight [g/mol]	Repeated dose toxicity Oral
627-89-4 (a)	Isopentyl oleate	326.56 - 354.61	RA: CAS 110-27-0 RA: CAS 91031-48-0
110-27-0 (b)	Isopropyl myristate	270.46	Experimental result: NOAEL =1000 mg/kg bw/day (rat)
91031-48-0 (b)	Fatty acids, C16-18, 2-ethylhexyl esters	368.65 – 396.7	Experimental result: NOEL =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 repeated dose toxicity is available with isopentyl oleate (CAS 627-89-4). Therefore, read across from the structurally analogue substances isopropyl myristate (CAS 110-27-0) and fatty acids, C16-18, 2-ethylhexyl esters (CAS 91031-48-0) was applied.

 

Repeated dose toxicity (oral)

CAS 110-27-0

A reliable key repeated dose toxicity study (28-day) with isopropyl myristate (CAS 110-27-0) is available and was performed equivalent or similar to OECD TG 407 (Gloxhuber, 1983). Only limited details on test substance purity are available. Groups of 10 Wistar rats of each sex were administered the test material at doses of 100, 500 and 1000 mg/kg bw/day or vehicle alone (olive oil) via oral gavage for 28 days on 5 consecutive days per week. Five additional animals per sex per dose were included as recovery group for analysis of possible post-exposure reversibility of intoxication symptoms. Urinalysis, neurobehavioural examinations and ophthalmoscopy were not performed.

Clinical observations, body weight changes, haematology, clinical chemistry, organ weight measurements as well as gross and histopathological examinations revealed no treatment-related abnormalities or adverse effects. Histopathology revealed hyperplastic changes in the non-glandular stomach of treated and control animals. Manifest mucosal hyperplasia was found in animals of the highest dose group. In few cases the mucosal hyperplasia was found combined with a submucosal inflammatory edema. In the recovery group these findings were not present in the non-glandular stomach, indicating the reversibility of the changes. The changes were judged to be induced by the olive oil used as vehicle and not by the test substance itself. Therefore, no treatment-related changes were observed. Based on the results of the study and due to the absence of any toxicological relevant adverse effect a subacute NOAEL of 1000 mg/kg bw/day was derived for isopropyl myristate.

 

CAS 91031-48-0

Another repeated dose toxicity study (28-day) with fatty acids, C16-18, 2-ethylhexyl esters (CAS 91031-48-0) is available and was performed equivalent or similar to OECD TG 407 (Pittermann, 1992). Only limited information on test substance purity is available. Urinalysis and neurobehavioural examination were not performed. Groups of 10 Sprague-Dawley rats of each sex were administered the test material at doses of 100, 500 and 1000 mg/kg bw/day or vehicle alone (peanut oil) via oral gavage for 28 days on 5 consecutive days per week. Five additional animals per sex were included in the control and highest dose group as recovery group for analysis of possible post-exposure reversibility of intoxication symptoms. In addition, 5 male and 5 female animals were used to determine the reversibility of possible compound-related findings (recovery group). All doses applied were tolerated without lethality. No compound-related effects were observed based on clinical signs, food consumption, water intake, body weight gain, haematological and clinical chemistry examinations, ophthalmoscopic examination, absolute and relative organ weights as well as macroscopical and histological examinations. Based on the results of the study and due to the absence of any toxicological relevant effect a subacute NOEL of 1000 mg/kg bw/day was derived for fatty acids, C16-18, 2-ethylhexyl esters.

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

Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
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 repeated dose toxicity do not meet the classification criteria according to Regulation (EC) 1272/2008, and are therefore conclusive but not sufficient for classification.