2-ethyl-2-(hydroxymethyl)-1,3-propanediyl dioleate

Endpoint summary

Description of key information

The  available subchronic repeated dose oral toxicity studies resulted in NOAEL of 1000 mg/kg bw/day or greater.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The available information comprises adequate, reliable (Klimisch score 2) study from 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 environmental fate, ecotoxicological and toxicological profile (refer to endpoint discussion for further details). The selected studies are 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

Repeated dose Toxicity

There are no data available for the repeated dose toxicity of 2-Ethyl-2-(hydroxymethyl)-1,3-propanediyl dioleate (CAS 25111-05-1). In order 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, 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 put 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, the substance listed below are selected as reference substances for hazard assessment.

Overview for repeated dose toxicity

CAS	oral NOAEL, rat (sex) mg/kg bw/day	Inhalation NOAEC, rat (sex) mg/L air	Dermal NOAEL, rat (sex) mg/kg bw/day
25111-05-1 Target substance	RA : CAS 403507-18-6 (90-day)	--	--
403507-18-6	NOAEL (m; f) >= 1000 mg/kg bw/day (90-day)	--	--

The above mentioned substances are considered to be similar on the basis of structural similarity resulting in similar properties and/or activities. The available endpoint information is used to predict the same endpoints for 2-Ethyl-2-(hydroxymethyl)-1,3-propanediyl dioleate (CAS 25111-05-1). A detailed analogue approach justification is provided in the technical dossier (see IUCLID Section 13).

Subchronic Oral Repeated Dose Toxicity

A 90-day oral feeding toxicity study with Fatty acids, C16-18 and C18-unsatd., branched and linear ester with trimethylolpropane (CAS 403507-18-6) was performed comparable to OECD Guideline 408 and under GLP conditions (McRae, 2004). Groups of 10 male and 10 female Sprague-Dawley rats were exposed to the substance at 5, 50 and 1000 mg/kg bw/day by gavage, 7 days/week for 90 days. Control animals (10 per sex and dose) received the concurrent vehicle, arachis oil. Observations and examinations of the animals included clinical signs, body weight, food consumption, haematology, clinical chemistry, organ weights, neurobehaviour, gross necropsy and histopathology. The daily oral administration of the test substance was tolerated without any adverse effects up to the high dose of 1000 mg/kg bw/day. There were no toxicologically significant effects on body weight, food consumption and clinical condition and mortality up to and including the highest dose level. Some incidental and spontaneous effects during histophathology examinations were observed but those were not due to the test substance administration. Therefore, a 90-day oral NOAEL >= 1000 mg/kg bw/day was found for Fatty acids, C16-18 and C18-unsatd., branched and linear ester with trimethylolpropane in male and female rats.

Conclusion for Repeated Dose Toxicity - Oral

In summary, the 90-day oral toxicity study with Fatty acids, C16-18 and C18-unsatd., branched and linear ester with trimethylolpropane (CAS 403507-18-6) shows no toxicologically significant effects on body weight, food consumption and clinical condition and mortality up to and including the highest dose level.

In conclusion, since the effects observed are not considered to be systemic and relevant for humans, the NOAEL was found to exceed 1000 mg/kg bw.

Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
Hazard assessment is conducted by means of read-across from structural analogue. The available study is adequate and reliable based on the identified similarities in structure and intrinsic properties between source and target substances and overall quality assessment (refer to the endpoint discussion for further details).

Justification for classification or non-classification

The available data on structural related substances for 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.