Fatty acids, C8-12, isopentyl esters

Endpoint summary

Description of key information

Based on a weight of evidence approach, Fatty acids, C8-12, isopentyl ester has no skin or eye irritating potential.

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)

Additional information

Irritation

Justification for read-across

There are no data regarding irritation available for Fatty acids, C8-12, isopentyl ester. In order to fulfil the standard data requirements defined in Regulation (EC) No 1907/2006, Annex VII and VIII, 8.1 and 8.2, read-across from appropriate substances is conducted in accordance with Regulation (EC) No 1907/2006, Annex XI, 1.5.

According to 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) “to avoid the need to test every substance for every endpoint”.

Fatty acids, C8-12, isopentyl ester is a multi-constituent substance specified by C8, C10 and C12 linear saturated fatty acids esterified with isopentanol resulting in monoesters which meets the definition of an UVCB substance. Thus, the test substance represents fatty acid esters which undergo to a high extent hydrolysis by ubiquitous expressed gastrointestinal enzymes into the free fatty acid components and the respective alcohol (Lehninger, 1970; Mattson and Volpenhein, 1972). Considering the common metabolism, the read-across approach is based on the presence of common functional groups, common precursors and the likelihood of common breakdown products via biological processes, which result in structurally similar chemicals, common functional groups, structural similarities and similar physico-chemical, toxicological and toxicokinetic behaviour. For further details on the read-across approach, please refer to the analogue justification in section 13 of the technical dossier.

As no data on irritation are available for Fatty acids, C8-12, isopentyl ester, read-across to reliable data on the analogue substances Isopropyl Myristate (CAS 110-27-0) and Isopropyl Laurate (CAS 10233-13-3) was conducted for skin irritation. Data on Isopropyl Laurate (CAS 10233-13-3) and 2-Ethylhexyl laurate (CAS 20292-08-4)were also applied in a read across approach to cover eye irritation toxicity. The substances were chosen based on their structural similarities regarding the branched alcohol component (isopropanol or 2-ethylhexanol) and the linear fatty acid component (C12 or C14).

Skin Irritation

CAS 110-27-0

A primary dermal irritation study was performed with Isopropyl Myristate (CAS 110-27-0) according to OECD guideline 404 and under GLP conditions (Mulder, 1986) in 3 female rabbits (New Zealand White). The shaved flank skin was exposed to 0.5 mL unchanged test material for 4 hours under semi-occlusive conditions. The rabbits were observed for 7 days. Skin reactions were assessed using the Draize scheme approx. 1, 24, 48 and 72 hours as well as 7 days after removal of the test substance.

The exposure period of 4 hours caused only very slight erythema (mean score (24, 48 and 72 h) for all animals = 1) in all animals that was fully reversible within 7 days. One rabbit showed slight edema (mean score (24, 48 and 72 h) = 0.66) up to 48 h after application.

CAS 10233-13-3

A primary dermal irritation study was performed with Isopropyl Laurate (CAS 10233-13-3) according to OECD guideline 404 (Dufour, 1991). The shaved skin of three rabbits was exposed to 0.5 mL unchanged test material for 4 hours under occlusive conditions. The rabbits were observed for 7 days. Skin reactions were assessed according to Directive 67/548/CEE approx. 1, 24, 48 and 72 hours as well as 7 days after removal of the test substance.

The exposure period of 4 hours caused only slight edema and erythema (mean score (24, 48 and 72 h) = 0.7, respectively) in one animal. The other two animals were free of any skin irritation. All treated skin sites appeared normal at the 72 hour observation.

 

Eye irritation

CAS 110-27-0

An acute eye irritation study with Isopropyl Myristate (CAS 110-27-0) was performed according to a protocol similar to OECD guideline 405 with 3 New Zealand White rabbits (Palanker, 1977). One eye of the rabbits was exposed to 0.1 mL of the undiluted test substance (no data on purity) and scored for eye reactions. The animals were observed for 7 days and scoring was performed 24, 48 and 72 h and 4 and 7 days after application. Only conjunctival redness (grade 1) was observed in two animals at the 24 h reading that was fully reversible within 48 h (mean score (24, 48, 72 h) = 0.33, respectively). No effects on conjunctival swelling, iris, or cornea were observed.

CAS 20292-08-4

An acute eye irritation test performed according to OECD guideline 405 to evaluate the eye irritation potential of 2-Ethylhexyl Laurate (CAS 20292-08-4) is available (Bouffechoux, 1996). The test substance (no data on purity) was instilled in the conjunctival sac of three New Zealand rabbits. The animals were observed for 7 days and scoring of iris, cornea and conjunctivae according to Draize was performed 1, 24, 48, 72 hours and 7 days after application. Slight conjunctival effects (mean score = 0.33 in all animals) were observed up to 24 h that were fully reversible within 48 h. No information is given if these effects were reddening or swelling of the conjunctivae as only a summary of the results is available. However, based on the results of the study the test substance is not considered eye irritating and classification is not warranted.   

In summary, it is concluded that the test material has no potential for eye irritation. Based on the obtained results, Isopropyl Myristate and 2-Ethylhexyl Laurate are not eye irritating.

Conclusion on skin and eye irritation properties

The skin and eye irritation properties of the read-across analogue substances have been investigated in vivo, indicating that they have no irritating properties towards the skin or eyes. Therefore, based on these data, Fatty acids, C8-12, isopentyl ester is not considered as skin or eye irritant.

 

References

A detailed reference list is provided in the technical dossier (see IUCLID, section 13) and within the CSR.

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 Fatty acids, C8-12, isopentyl ester, data will be generated from information on 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 target substance information and analogue read-across approach, the available data on skin and eye irritation do not meet the classification criteria according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.