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Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

OECD 471: In vitro bacterial reverse mutation assay: Negative

OECD 473: In vitro chromosome aberration assay using Chinese Hamster lung cells (CHL/IU): Negative

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

In a key Guideline OECD 471 study (Safety Research Institute for Chemical Compounds Co., Ltd, 2015), the potential of the test material (HCFO-1233yd(Z)) to induce genetic mutation in bacteria was evaluated in a bacterial reverse mutation assay using Salmonella typhimurium strains TA98, TA100, TA 1535, TA1537 and Escherichia coli strain WP2uvrA in the absence and presence of metabolic activation (±S9).

In the study, a dose-finding test was conducted initially where the highest dose of the test substance was set at 5000 µg/plate and a total of 7 doses (5, 15, 50, 150, 500, 1500, and 5000 µg/plate) were set in approximately threefold dilution series for both the non-activated and activated assays. On the basis of the results of the dose-finding test, 5000 µg/plate was selected as the highest dose of the test substance and total of 6 doses were set in a twofold dilution series (5-step serial dilutions) for all tester strains in both the non-activated and activated assays (Main test: ±S9: 156, 313, 625, 1250, 2500, and 5000 µg/plate).

In the dose-finding as well as the main test, in both the non-activated and activated assays, the average number of revertants in the test substance group was less than twice that in the corresponding negative control group in all tester strains and the number of revertants did not increase in a dose-related manner. No inhibition of cell growth or precipitation of the test substance was observed in an tester strain. Thus, reproducibility was obtained between the results of the dose-finding test and those of the main test.

 

In the dose-finding as well as the main test, all the average number of revertants in the negative control group of all tester strains were within the range of control values based on the historical control data of the test facility. The average number of revertants in the positive control group of each tester strain clearly increased and was twice or more that in the corresponding negative control group. These results confirmed that each tester strain had appropriate sensitivity to the mutagens.

 

Based on the results observed, the test material was not considered to be mutagenic under the conditions of this bacterial reverse mutation assay.

In a key OECD Guideline 473 study (Safety Research Institute for Chemical Compounds Co., Ltd, 2016), the clastogenic potential of the test material (HCFO-1233yd(Z)) was investigated in vitro using Chinese Hamster lung cells (CHL/IU). The test material was evaluated in three test series: short-term treatment without S9 (-S9 treatment); short-term treatment with S9 (+S9); and continuous 24-hour treatment (24-hr treatment). 

 

In the preliminary cell growth inhibition test (concentrations: 10.9, 21.9. 43.8, 87.5, 175, 350, 700, and 1400 µg/mL), precipitation was observed at the beginning and end of treatment with the 1400 µg/mL test solution in the three test series. No effects on the pH of the culture solution were observed in any test series. With respect to effects on cell growth, although a tendency to inhibit cell growth was noted in all test series, inhibition of cell growth exceeding 50% was not detected in any test series.

 

Based on the results of the preliminary test, 175, 350, 700, and 1400 µg/mL were selected for all test series in the main chromosome aberration test. Precipitation was observed at the beginning and end of treatment with the 1400 µg/mL test solution in the three test series. No effects on the pH of the culture solution were observed in any test series.

 

Based on the results of effects on cell growth, 350, 700, and 1400 µg/mL were selected as the doses for observation of chromosome specimens for all three test series. There were no significant increases in the incidence of structural or numerical aberrations of chromosomes in the test substance group in any test series.

 

Incidence of structural and numerical aberrations of chromosomes in the negative control groups of all test series were within the control range based on the historical control data. The incidence of structural aberrations of chromosomes in the positive control group of all test series were within the control range based on the historical control data, and a statistically significant increase was noted compared with the negative control group.

 

Treatment with the test material resulted in no increase in the incidence of structural or numerical aberrations of chromosomes. Based on the results observed, the test material is was not considered to be clastogenic to cultured mammalian cells under the conditions of this in vitro chromosome aberration test.

Justification for classification or non-classification

The available in vitro data indicates that classification for genotoxicity is not warranted.

HCFO-1233yd(Z) is not classified according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008 or UN Globally Harmonized System of Classification and Labelling of Chemicals (GHS).