Dodecanoic acid, ester with oxybis[propanediol]

Endpoint summary

Additional information

No data are available on the genetic toxicity of Reaction product of lauric acid and oxybis(propanediol) (List No. 700-672-1) in vitro and in vivo.

Therefore, available data on the structural surrogates 2,3-dihydroxyproypl laurate (CAS No. 142-18-7) and glycerol oleate (CAS No. 111-03-5) as well as on short- and long-chain fatty acid triacylglycerols were considered for assessment and read-across was conducted based on an analogue and weight of evidence approach.

In vitro

A bacterial gene mutation assay (Ames test) was performed with 2,3-dihydroxypropyl laurate (CAS No. 142-18-7) following OECD guideline 471 under GLP conditions in Salmonella typhimurium TA 98, TA 100, TA 1535 and TA 1537 (Banduhn, 1995). In the first experiment the direct plate incorporation procedure was performed at concentrations up to 5000 µg/plate with and without a metabolic activation system (Aroclor 1254-induced rat liver S9-mix). In a second analogue experiment concentrations up to 100 µg/plate were tested.

Two independent experiments were conducted, in which the background lawn was reduced or completely cleared at concentrations of 40 µg/plate and above. The included positive and negative controls in the experiments showed the expected results and were therefore considered to be valid. No increase in the number of revertant colonies was noted in any of the bacterial strains, in concentrations below cytotoxic effects, with and without metabolic activation system.

Under the conditions of the study, 2,3-dihydroxypropyl laurate did not induce mutations in the bacterial mutation test in the absence and presence of a metabolic activation system in any of the strains tested.

Glycerol oleate (CAS No. 111-03-5) was tested in an in vitro mammalian chromosome aberration test conducted in accordance with GLP and OECD guideline 473 (Nakajima). The induction of structural chromosome aberrations was evaluated in Chinese hamster lung (CHL/IU) cells incubated for 6 h with and without metabolic activation (S9-mix from rats treated with phenobarbital and 5,6-benzoflavone) and for 24 h without metabolic activation. Concentrations of 891-3565 µg/mL (6 h incubation) and 55.7-446 µg/mL (24 h incubation) of the test substance in DMSO were applied.

In a range-finding study, cytotoxicity was evaluated after a continuous 24 h exposure (without metabolic activation) and after 6 h (with and without metabolic activation) at concentrations of 6.96-3565 µg/mL and the IC50 value for cell growth inhibition after 24 h was identified to be 2738 µg/mL. In the main study, cytotoxicity was observed at 446 µg/mL after 24 h treatment. No increase in incidence of chromosome aberrations was observed under the conditions in the study. The included negative and positive controls showed the expected results.

Under the conditions of the study, the test substance did not show clastogenic activity in this chromosomal aberration test performed in CHL/IU cells.

In an in vitro mammalian cell gene mutation assay in Chinese hamster ovary cells (CHO), short- and long-chain acyl triglycerides were tested in a protocol similar to the OECD guideline 476 (Hayes, 1994). Gene mutations in the HPRT locus were investigated in the presence and absence of a metabolic activation system (S9-mix from rats treated with Aroclor 1254) in two independent experiments at concentrations of 31.25, 62.5, 125, 250, 500 and 1000 µg/mL of the test material (diluted in acetone).

The included negative and positive controls in the main study showed the expected results and were therefore concluded to be valid. No cytotoxic effects of the test material were reported.

The test substance did not induce an increase in the mutant frequency in the HPRT locus in CHO cells, neither in the presence nor in the absence of a metabolic activation system, under these experimental conditions.

 

In vivo

The potential of short- and long-chain acyl triglycerides to induce chromosomal damage in vivo was investigated within an oral subchronic toxicity study equivalent to OECD guideline 474 (Hayes, 1994). The test material was administered to groups of 20 Crl:CD BR VAF/Plus rats per sex as 10% preparation in the diet (corresponding to 7000 mg/kg bw/day) for 13 weeks. As concurrent vehicle control corn oil was mixed with the diet. No positive control was included, because the test material was collected from a 13 week subchronic toxicity study. At necropsy, duplicate bone marrow slides for each rat were prepared for clinical pathology.

No toxic effects were observed during the study period. The test material did not induce an increase in the number of micronucleated polychromatic erythrocytes in the bone marrow of the animal groups in comparison with the control group.

Thus, under the experimental conditions, short- and long-chain acyl triglycerides did not induce micronuclei in the polychromatic erythrocytes of the bone marrow of rats in concentrations of 10% in the diet, corresponding to approximately 7000 mg/kg bw/day.

In summary, the structural surrogates of Reaction product of lauric acid and oxybis(propanediol) (List No. 700-672-1) showed no genetic toxicity in vitro and in vivo in different test systems.

Justification for selection of genetic toxicity endpoint
Hazard assessment is conducted by means of read-across from structural surrogates. No study was selected, since all available in vitro and in vivo 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 substance and overall quality assessment (refer to the endpoint discussion for further details).

Short description of key information:
Based on read-across from surrogate substances following an analogue approach the substance Reaction products of lauric acid and oxybis(propanediol) is not genotoxic.
Negative results in Salmonella typhimurium TA 98, TA 100, TA 1535 and TA 1537, with and without metabolic activation (OECD 471, GLP).
Negative results in mammalian chromosomal aberration test with Chinese hamster lung cells (OECD 473, GLP).
Negative results in mammalian cell gene mutation tests using Chinese hamster ovary cells, with and without metabolic activation (OECD 476, GLP).

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Based on read-across from surrogate substances following an analogue approach, the available data on the genetic toxicity of Reaction product of lauric acid and oxybis(propanediol) (List No. 700-672-1) do not meet the criteria for classification according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and the data are therefore conclusive but not sufficient for classification.