Registration Dossier

Administrative data

Key value for chemical safety assessment

Additional information

Genetic toxicity

There are no data available on genetic toxicity of Fatty acids, vegetable-oil, esters with dipropylene glycol. In accordance with Regulation (EC) No 1907/2006, Annex XI, 1.5 read-across from appropriate substances is conducted to fulfill the standard information requirements set out in Regulation (EC) No 1907/2006, Annex VIII, 8.5.

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, vegetable-oil, esters with dipropylene glycol is a UVCB substance comprised of diesters based on 1,2-dipropylene glycol bonded tooctanoic and decanoic acid(C8 – C10). Based on structural similarities and common functional groups, read-across to the analogue substances Decanoic acids, mixed diesters with octanoic acid and propylene glycol (CAS 68583-51-7), C8-C10-1,3-Butandiolester (853947-59-8) and Fatty acids, C16-18, esters with ethylene glycol (CAS 91031-31-1) was conducted. For further details on the read-across approach, please refer to the analogue justification in section 13 of the technical dossier.

 

Genetic toxicity (mutagenicity) in bacteria in-vitro

CAS 68583-51-7

A bacterial gene mutation assay was performed with Decanoic acid, mixed diesters with octanoic acid and propylene glycol following OECD guideline 471 and in compliance with GLP (Banduhn, 1991). The strains Salmonella typhimurium TA 98, TA 100, TA 1535, TA 1537 and TA 1538 were tested in two independent experiments according to the plate incorporation procedure at concentrations from 8 to 5000 µg/plate (vehicle: suspension medium Tween 80/bidest. water) with and without a metabolic activation system (Aroclor 1254-induced rat liver S9-mix). No increase in the number of revertant colonies was noted in any strain of bacteria tested, with and without a metabolic activation system. No cytotoxicity was observed up to the highest dose tested. The included positive and negative controls showed the expected results and were therefore considered as valid. Under the conditions of this study, the test substance did not induce mutations in the bacterial mutation tests in the absence and presence of a metabolic activation system in any of the strains tested (Banduhn, 1991).

 

Genetic toxicity (cytogenicity) in mammalian cells in-vitro

CAS 853947-59-8

An in vitro mammalian chromosome aberration test was conducted with C8-C10-1,3-Butandiolester in accordance with OECD guideline 473 under GLP conditions (Dechert, 1997). The induction of structural chromosome aberrations was evaluated in vitro in Chinese hamster lung fibroblasts (V79) cells, incubated for 18 and 28 h with and without a metabolic activation system (S9-mix from rats treated with Aroclor 1245). Concentrations of 10-100 µg/mL (18 h incubation) and 80 and 100 µg/mL (28 h incubation) of the test substance in the vehicle ethanol were applied. The solubility limit of the test substance in the vehicle ethanol in the culture medium was determined to be 100 µg/mL. In the first experiment without metabolic activation, the negative controls exhibited a mitotic index of 2.0% only and the experiment was therefore repeated. Thereafter, the negative as well as the positive controls showed the expected results and were within the range of historical control data. The frequency of polyploidy cells with and without metabolic activation was within the expected range (< 10%). In the experiments both with and without metabolic activation, a systematic influence of the test substance was observed, which led to a reduction in the mitotic index. No statistically or biologically significant increase in the incidence of chromosome aberrations was observed.

Therefore, under the conditions of the study, C8-C10-1,3-Butandiolester did not show clastogenic activity in this chromosomal aberration test with and without metabolic activation performed in Chinese hamster lung fibroblasts in vitro.

 

Genetic toxicity (mutagenicity) in mammalian cells in-vitro

CAS 91031-31-1

Mutagenic properties of Fatty acids, C16-18, esters with ethylene glycol were characterized in an in vitro mammalian cell gene mutation study according to OECD guideline 476 under GLP conditions (Verspeek-Rip, 2010). Gene mutations in the thymidine kinase locus were investigated in L5178Y mouse lymphoma cells in the presence and absence of a metabolic activation system (Phenobarbital/β-naphtoflavone-induced rat liver S9). In the first experiment, cells were exposed for 3 h to test substance at concentrations of 0.1-333 µg/mL (in DMSO) with and without metabolic activation. Concentrations of the second experiment without metabolic activation for an exposure time of 24 h ranged from 3-175 µg/mL and with metabolic activation (3 h; 12% S9-mix) from 0.1-333 µg/mL. The vehicle and positive controls in the study showed the expected results and were within the range of historical control data. No cytotoxicity was observed up to the precipitating concentration of 100 µg/mL and up to 333 µg/mL, respectively. There was no significant increase in the number of forward mutations at the thymidine kinase locus of L5178Y mouse lymphoma cells treated with the test material, neither in the presence nor in the absence of a metabolic activation system. Under the conditions of the study, Fatty acids, C16-18, esters with ethylene glycol did not show gene mutation activity in this test performed in L5178Y mouse lymphoma cells in vitro.

 

Conclusion for genetic toxicity

The available data on read-across analogue substances do not provide evidence that Decanoic acid, mixed diesters with octanoic acid and propylene glycol (CAS 68583-51-7), C8-C10-1,3-Butandiolester (853947-59-8) or Fatty acids, C16-18, esters with ethylene glycol (CAS 91031-31-1) exhibit mutagenic or clastogenic properties in either bacterial or mammalian cells. Therefore, no properties for genetic toxicity are expected for Fatty acids, vegetable-oil, esters with dipropylene glycol.


Justification for selection of genetic toxicity endpoint
Hazard assessment is conducted by means of a read-across based on a read-across from structural analogues. 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:
Gene mutation (OECD 471): CAS 68583-51-7: negative with and without metabolic activation in S. typhimurium TA 98, TA 100, TA 1535, TA 1537 and TA 1538
Chromosome aberration (OECD 473): CAS 853947-59-8: negative in Chinese hamster lung fibroblasts (V79) cells with and without metabolic activation
Gene mutation (OECD 476): CAS 91031-31-1: negative in L5178Y mouse lymphoma cells with and without metabolic activation

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

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.