Octa-1,7-diene

Endpoint summary

Additional information

in vitro:

Gene mutation in bacteria

The potential mutagenicity of 1,7-octadiene was investigated in two bacterial reverse mutation assay (Ames test) similar and according to OECD Guideline 471 under GLP conditions (91-0240-DGM, 2014 -0032 -DGM). Salmonella typhimurium strains TA 98, TA 100, TA 1535, TA 1537, TA 1538 and E. coli WP2 were treated with the test substance at concentrations up to 5000µg/plate using the plate incorporation assay and pre-incubation method, respectively.

Both experiments were performed in the absence and presence of a liver microsomal activation system (S9 mix). Cytotoxicity was observed in all strains in the pre-incubation method and in strain TA 1537 in the plate incorporation assay at the highest concentration (5000µg/plate) without metabolic activation. The induced number of revertants per plate was comparable to the vehicle control for all strains tested with and without S9 mix. The positive controls included showed the expected results. Thus, under the experimental conditions reported, the test substance did not induce mutations in the absence and presence of metabolic activation in the selected strains of S. typhimurium and E. coli.

 

Cytogenicity in mammalian cells

An in vitro mammalian chromosome aberration test was performed with 1,7-octadiene in human lymphocytes according to OECD Guideline 473 and in compliance with GLP (2009-0124-DGM). The test substance concentrations for chromosome analysis were selected in a preliminary cytotoxicity assay using ten test concentrations in the range of 10 – 5000 µg/mL. Pronounced cytotoxicity in form of haemolysis was noted at concentrations of 100 µg/mL and above with and without S9 mix. In the main test, concentrations of 15.63, 31.3, 62.5 and 125 µg/mL medium were used to analyse chromosomal aberrations after exposure to the test substance for 4 h and 24 h in the absence of metabolic activation and for 4 h in the presence of metabolic activation. The experiment with metabolic activation was carried out twice. Cells were harvested 24 h after start of exposure. Pronounced cytotoxicity was noted at the top concentration of 125 µg/mL in the experiments with and without S9 mix. Frequency of structural aberrations and number of aberrant cells (excluding gaps) ranged from 0.5% – 2% in experiments with (15.63 – 62. 5 µ/mL) and without S9 mix (15.63 – 125 µg/mL) and were considered to be within the normal range of the solvent control. At the highest concentration (125 µg/mL) in the experiments with S9 mix, the frequency of cells with numerical aberrations increased marginal. This was considered to be an artefact caused by the high cytotoxicity and not test substance-related. No polyploidy or endoreduplication were noted in the experiments with and without S9 mix. The positive controls showed the expected increase in the rate of chromosome aberrations, thus indicating the sensitivity of the assay.

It is concluded that the test substance did not induce chromosome aberrations in cultured human peripheral blood lymphocytes when tested to the limit of cytotoxicity and is therefore considered not to be clastogenic.

 

Gene mutation in mammalian cells

1,7-Octadiene was tested for its potential to induce mutation at the hypoxanthine guanine phosphoribosyl transferase (HPRT) locus in Chinese Hamster Ovary Cells (CHO) according to OECD Guideline 476 under GLP conditions (90-0204-DGM). In a dose- range finding study, no cytotoxicity was noted up to a concentration of 1 mg/mL, which was determined to be the maximum solubility of 1,7-octadiene in the culture medium. In the main test CHO cells were treated with test substance concentrations of 0.05, 0.1, 0.5, 0.75 and 1.0 mg/mL both in the absence and presence of metabolic activation for 4 h in two independent experiments. The treatment of cells in all experiments was followed by an expression period of 8 days and a selection period of 6-7 days in the presence of 6-thioguanine.

No increases in mutation frequency above the normal spontaneous mutation frequency of approx. maximum 20 mutants per 1E+06 cells were observed following treatment with the test substance at any concentration tested. The positive controls significantly increased mutant frequency, demonstrating the sensitivity of the test system and the efficacy of the metabolic activation system. Thus, based on the test result 1,7-octadiene was not mutagenic in the mammalian cell gene mutation assay (HPRT assay). 

 

In conclusion, 1,7-octadiene is considered not to cause genetic damage, since all in vitro genetic toxicity studies revealed negative results.

 

in vivo:

No data on in vivo genetic toxicity is available.

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

Short description of key information:
in vitro:
Gene mutation in bacteria (Bacterial reverse mutation assay / Ames test): negative with and without metabolic activation in S. typhimurium strains TA 98, TA 100, TA 1535, TA 1537 and TA 1538 (similar to OECD 471)
Cytogenicity in mammalian cells (Mammalian chromosome aberration test): negative with and without metabolic activation in human peripheral lymphocytes (OECD 473)
Gene mutation in mammalian cells (mammalian cell gene mutation test / HPRT test): negative with and without metabolic activation in CHO cells (OECD 476)

in vivo: no further testing required

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

The available data on genetic toxicity of 1,7-octadiene do not meet the criteria for classification according to Regulation (EC) 1272/2008, and are therefore conclusive but not sufficient for classification.