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Overview of genetic toxicity

CAS

Bacterial gene mutation

Cytogenicity in mammalian cells in vitro

Mammalian gene mutation

63705-03-3

negative

negative

negative

In vitro gene mutation in bacteria

A bacterial gene mutation assay (Ames test) was performed with 1,2,3-Propanetriol, homopolymer, diisooctadecanoate, (CAS# 63705-03-3) with a method equivalent or similar to OECD Guideline 471 and under GLP conditions (Banduhn, 1988). The plate incorporation procedure was performed with Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 1538 and TA 100 in the absence and presence of metabolic activation (Aroclor 1254-induced rat liver S9-mix). Two experiments were conducted each in triplicates at concentrations 8, 40, 200, 1000 and 5000 µg/plate with and without metabolic activation (vehicle: Tween 80/bidistilled water). No increase in the number of revertant colonies was noted in any of the bacterial strains, with and without metabolic activation system. No cytotoxicity was observed up to the highest dose tested. The included positive and negative controls showed the expected results. Under the study conditions, the test substance did not induce mutations in the bacterial mutation assay in the absence and presence of a metabolic activation system in any of the strains tested.

In vitro gene mutation in mammalian cells

The substance 1,2,3-Propanetriol, homopolymer, diisooctadecanoate (CAS 63705-03-3) was assessed for its potential to induce gene mutations at the hypoxanthine-guanine phosphoribosyl transferase (HPRT) locus in Chinese hamster ovary (CHO) cells in vitro according to OECD TG 476 and under GLP conditions (Kapp, 2013). Two independent experiments were carried out, both with and without the addition of liver S9 mix (phenobarbital- and beta-naphthoflavone). According to an initial range-finding cytotoxicity test for the determination of the experimental doses and taking into account the cytotoxicity actually found in the main experiments, the following doses were tested. In the first experiment cells were exposed in duplicate to the test substance dissolved in DMSO at concentrations of 3.13; 6.25; 12.50; 25.00; 50.00; 100.00 µg/mL without and with S9 mix.

In the second experiment cells were exposed in duplicate to the test substance dissolved in DMSO at concentrations of 9.38; 18.75; 37.50; 75.00; 150.00; 200.00 µg/mL without S9 mix and at concentrations of 4.69; 9.38; 18.75; 37.50; 75.00; 150.00 µg/mL with S9 mix.

Following attachment of the cells for 20-24 hours, cells were treated with the test substance for 4 hours in the absence of metabolic activation and for 4 hours in the presence of metabolic activation. Subsequently, cells were cultured for 6-8 days and then selected in 6-thioguanine-containing medium for another week. Finally, the colonies of each test group were fixed with methanol, stained with Giemsa and counted.

The vehicle controls gave mutant frequencies within the range expected for the CHO cell line. Both positive control substances, EMS and DMBA, led to the expected increase in the frequencies of forward mutations.

In this study, in the 1st and 2nd Experiment, at least the highest concentrations evaluated for gene mutations were clearly cytotoxic in the absence and the presence of metabolic activation.

Based on the results of the present study, the test substance did not cause any relevant increase in the mutant frequencies either without S9 mix or after the addition of a metabolizing system in two experiments performed independently of each other.

Thus, under the experimental conditions of this study, the test substance 1,2,3-Propanetriol, homopolymer, diisooctadecanoate is not mutagenic in the HPRT locus assay under in vitro conditions in CHO cells in the absence and the presence of metabolic activation.

In vitro cytogenicity in mammalian cells

An in vitro mammalian chromosome aberration test was performed with 1,2,3-Propanetriol, homopolymer, diisooctadecanoate (CAS 63705-03-3) in V79 cells in vitro according to OECD TG 473 and under GLP conditions (Schulz, 2013). Duplicate cultures of V79 cells were evaluated for chromosome aberrations in the presence and absence of metabolic activation (rat liver S9-mix).

The test substance induced cytotoxicity in the second experiment at 800 μg/mL and in the third experiment from 200 μg/mL onward at 18 hours sampling time and from 400 μg/mL onward at 28 hours sampling time. Cells were exposed for 4 hours to the test substance dissolved in DMSO at concentrations of 3.13, 6.25, 12.5, 25, 50, 100, and 200 µg/mL with and without metabolic activation during the first experiment. Cells were exposed for 4 hours at concentrations of 12.5, 25, 50, 100, 200, 400 and 800 µg/mL with and without metabolic activation during the second experiment. During the third experiment cells were exposed to the test substance for 18 hours with and without metabolic activation and for four hours with metabolic activation at concentrations of 12.5, 25, 50, 100, 200, 400 and 800 µg/mL.

A sample of 100 metaphases for each culture was analyzed for chromosomal aberrations, except for the positive control cultures where only 50 metaphases were scored due to clearly increased aberration rates.  The vehicle controls gave frequencies of aberrations within the range expected for the V79 cell line. Both positive control substances (EMS and cyclophosphamide) led to the expected increase in the number of cells containing structural chromosome aberrations.

On the basis of the results of the present study, the test substance did not cause any biologically relevant increase in the number of structurally aberrant metaphases at both sampling times either without S9 mix or after adding a metabolizing system.  

No biologically relevant increase in the frequency of cells containing numerical chromosome aberrations was demonstrated either.

Thus, under the experimental conditions, 1,2,3-Propanetriol, homopolymer, diisooctadecanoate (CAS 63705-03-3) is considered not to have a clastogenic effect under in vitro conditions in V79 cells in the absence and the presence of metabolic activation.

Conclusions

In summary, three studies investigating respectively the genetic mutation in bacteria in-vitro, the in-vitro gene mutation in mammalian cells, and the in vitro cytogenicity in mammalian cells are available with 1,2,3-Propanetriol, homopolymer, diisooctadecanoate (CAS# 63705-03-3) providing negative results.


Justification for selection of genetic toxicity endpoint
No study was selected, since all available studies were negative.

Short description of key information:
Negative results in Salmonella typhimurium TA 98, TA 100, TA 1535, TA 1537 and TA 1538 with and without metabolic activation (OECD 471, GLP).
Negative results in mammalian citogenicity using Chinese hamster lung fibroblasts (V79) (OECD 473, GLP)
Negative results in mammalian cell gene mutation tests using Chinese hamster ovary (CHO), with and without metabolic activation (OECD 476, GLP)

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Based on 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.