Registration Dossier

Administrative data

Key value for chemical safety assessment

Additional information

Analogue justification

Data on the genetic toxicity of 1,2,3-propanetriyl triisooctadecanoate (CAS No. 26942-95-0) 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) and within Chapter 5.1 of the CSR.

Genetic toxicity (mutagenicity) in bacteria in vitro

CAS No. 26942-95-0

The potential mutagenicity of 1,2,3-propanetriyl triisooctadecanoate was assessed in four S. typhimurium strains (TA 1535, TA 1537, TA 98 and TA 100) in an Ames test similar to OECD Guideline 471 and under GLP conditions (Waart van de, 1996). Concentrations ranging from 100 to 5000 µg/plate were selected for treatment in the main assay. Precipitation was observed in the first experiment at the maximum concentration of 5000 µg/plate, which however did not influence the counting of revertant colonies. No increase in the mean number of revertants per plate was observed when compared with controls. The positive and negative controls included for each tester strain were shown to be valid. Based on the study results, the test substance was considered non-mutagenic in the selected strains of S. typhimurium in the presence and absence of metabolic activation.

Genetic toxicity (cytogenicity) in mammalian cells in vitro

Short-, medium- and long-chain triglycerides (SCT, MCT, LCT)

An in vitro mammalian chromosome aberration test with the SALATRIM (short- and long-chain acyl triglyceride molecules) family of triacylglycerols was performed similar to OECD guideline 473 in Chinese hamster Ovary (CHO) cells (Hayes et al., 1994). In a preliminary toxicity test, concentrations of 8 - 1000 μg/mL were used to determine suitable concentrations for chromosome analysis. Based on these results, the occurrence of chromosome aberrations was investigated in the presence and absence of metabolic activation (rat liver S9-mix) with test substance concentrations of 250, 500 and 1000 µg/mL. The exposure duration was 2 and 8 hours with and without metabolic activation, respectively, while the harvest time was 8-10 h (with and without metabolic activation). The highest dose was chosen based on the low solubility of the fats in the assay medium. No significant increase in the number of phases with aberrations was observed in treated CHO cells at any preparation time and concentration. No significant cytotoxic effects were reported. The positive controls significantly increased the rate of chromosome aberrations. In conclusion, the test substance was not clastogenic in Chinese hamster ovary cells in vitro, neither in the presence nor in the absence of a metabolic activation system, under the experimental conditions chosen.

Genetic toxicity (mutagenicity) in mammalian cells in vitro

Short-, medium- and long-chain triglycerides (SCT, MCT, LCT)

The SALATRIM (short- and long-chain acyl triglyceride molecules) family of triacylglycerols was assessed using a gene mutation assay in cultured mammalian cells (Chinese hamster ovary (CHO-K1) cells) similarly to OECD guideline 476 (Hayes et al., 1994). Gene mutations at the HPRT locus were investigated in the presence and absence of metabolic activation (rat liver S9-mix) with concentrations of 31.25, 62.5, 125, 250, 500 and 1000 µg/mL. Two cultures were tested per dose level. The highest concentration was limited by the low solubility of the fats in the assay medium. No significant cytotoxicity was reported. An increase in mutant frequency was not observed at any concentration tested whether with or without metabolic activation. The positive controls significantly increased the mutant frequency. Therefore, it was concluded that under the conditions of the study, the test material was not mutagenic at the HPRT locus of Chinese hamster ovary cells in the absence and presence of metabolic activation.

Overall conclusion for genetic toxicity

The target substance 1,2,3-propanetriyl triisooctadecanoate (CAS No. 26942-95-0) was shown not to induce gene mutations in bacteria. There are no available studies on the genetic toxicity of 1,2,3-propanetriyl triisooctadecanoatein mammalian cells. Therefore analogue read-across from source substances was applied from in vitro studies on cytogenicity and gene mutations in mammalian cells,using 2 source substances. The results of the available in vitro studies were negative.

Based on the available data and following the analogue approach, 1,2,3-propanetriyl triisooctadecanoate is considered to be not mutagenic in vitro and not clastogenic in vitro.


Justification for selection of genetic toxicity endpoint
Hazard assessment is conducted by means of read-across from structural analogues. No study was selected, since all available in vitro genetic toxicity studies were negative. All available studies are 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).

Short description of key information:
Genetic toxicity in vitro:
Ames test (OECD 471): negative with and without metabolic activation in S. typhimurium TA 1535, TA 1537, TA 100 and TA 98
Gene mutation in mammalian cells (OECD 476): negative in Chinese hamster ovary (CHO) cells with and without metabolic activation
Cytogenicity in mammalian cells (OECD 473): negative in Chinese hamster ovary (CHO) cells with and without metabolic activation

Endpoint Conclusion: No adverse effect observed (negative)

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 1,2,3-propanetriyl triisooctadecanoate (CAS No. 26942-95-0), 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 genetic 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.