Fatty acids, C12-18 (even-numbered), 3-methylbutyl esters

Endpoint summary

Description of key information

Oral (OECD 408), rat: NOAEL (systemic) =  1000 mg/kg bw/day

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:

subchronic

Species:

rat

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 precursors and breakdown products of hydrolysis and consistent trends in environmental fate, ecotoxicological and toxicological profile (refer to the endpoint discussion for further details). 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 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 read-across

Data on the repeated dose toxicity of Fatty acids, C12-18, even numbered, 3-methylbutyl esters (CAS 1314963-50-2) are not available. The assessment was therefore based on studies conducted with analogue substances as part of a read across approach, which is in accordance with Regulation (EC) No. 1907/2006, Annex XI, 1.5. For each specific endpoint the source substance(s) structurally closest to the target substance is/are chosen for read-across, with due regard to the requirements of adequacy and reliability of the available data. Structural similarities and similarities in properties and/or activities of the source and target substance are the basis of read-across. A detailed justification for the analogue read-across approach is provided in the technical dossier (see IUCLID Section 13).

CAS 163961-32-8

A 90-day oral gavage toxicity study with Fatty acids, C16-18 and C18-unsatd, branched and linear, butyl esters (CAS 163961-32-8) was performed according to OECD guideline 408 and in compliance with GLP (McRae, 2004). Groups of 10 male and female Sprague-Dawley rats received daily oral gavage doses of the test substance in arachis oil at concentrations of 0, 5, 50 and 1000 mg/kg bw/day. Animals were observed for clinical signs, body weight, food consumption, food efficiency, water consumption, ophthalmoscopic examination, haematology, clinical chemistry, neurobehavioral examination, organ weights, gross necropsy and histopathological examinations.

At 1000 mg/kg bw/day slightly elevated plasma cholesterol and creatinine levels were detected for males and a marginal effect on hepatocyte size was observed histopathologically in females. Males and females treated with 1000 mg/kg bw/day showed increased liver weight. Furthermore, at 1000 mg/kg bw/day males showed an increase in spleen weight and females showed an increase in adrenal and kidney weight, respectively. No such effects were detected among animals from the remaining treatment groups. These effects were considered to be adaptive responses and not adverse effects due to the absence of any supporting histopathological evidence. Therefore a 90-day oral NOAEL of 1000 mg/kg bw/day was considered for Fatty acids, C16-18 and C18-unsatd., branched and linear, butyl esters in male and female rats.

CAS 34316-64-8

A 90-day oral feeding toxicity study with Hexyl laurate (CAS 34316-64-8) was performed according to OECD guideline 408 (Potokar, 1973). Groups of 10 male and female Wistar rats were continuously exposed to the substance at 10000 ppm in the diet via an automatic feeding system (approximately 800 mg/kg bw/day) for 90 days. Control animals received liquefied margarine. Animals were observed for clinical sings, body weight, food consumption, food efficiency, water consumption, haematology, clinical chemistry, urinalysis, organ weights, gross necropsy and histopathological examinations.

Overall there were no adverse effects found after feeding of the animals with the test substance for 16 weeks. Changes in the liver and lung observed frequently occur in untreated ageing animals of both sexes and therefore, are not considered as adverse effects. Therefore the NOAEL was 800 mg/kg bw/day for hexyl laurate in male and female rats.

Overall conclusion for repeated dose toxicity

The data on the read-across analogue substances showed that no adverse effects were observed up to and including the recommended limit value of 1000 mg/kg bw/day. Therefore, as the available data did not identify any hazard for repeated dose toxicity, Fatty acids, C12-18, even numbered, 3-methylbutyl esters is not considered to be hazardous following repeated exposure.

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 the source and target substances and overall quality, duration and dose descriptor level (refer to the endpoint discussion for further details).

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, C12-18, even numbered, 3-methylbutyl esters (CAS 1314763-50-2) 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 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.