Oct-2-ene

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

In a reverse gene mutation assay in bacteria (Glueck 1983) , strains TA98, TA100, TA1535, TA1537, and TA1538 of S. typhimurium were exposed to the read-across source Neodene 8 Alpha Olefin in ethanol at concentrations of 1.4 x 10-4, 4.5 x 10-4, 1.4 x 10-3, 4.5 x 10-3, 1.4 x 10-2, 4.5 x 10-2, 0.14, 0.45 mg/plate in the presence and absence of mammalian metabolic activation using the pre-incubation method.

There was no evidence or a concentration related positive response of induced mutant colonies over background for the test material at any concentration tested.

A chromosome aberration assay was conducted by exposing the CHO cells to 6 concentrations of the read across source substance Neodene-8 alpha olefin prepared in ethanol. Concentrations of the test chemical ranged from, 1.0 X 10-2mg/mL to 1.0X10 -3mg/mL in 1/5 log10dilutions. Cells were exposed both, in the presence and absence of S9 fractions.

Following termination of exposures, study authors reported that concentrations of ≥0.072 mg/mL Neodene 8 alpha olefin were cytotoxic to CHO cells. They also reported that Neodene 8 alpha olefin did not induce aberrations in the absence of S9. In the presence of S9, the mean aberrations per cell exceeded the solvent control by 2-fold or more at the 5 highest concentrations tested. In addition, the percent abnormal cells exceeded the solvent controls by 2-fold or more at 3 nonconsecutive concentrations. The increases, however, were only slightly over 2-fold and were not concentration dependent.

Read-across of these results to Oct-2 -ene is claimed as valid based on the justifications provided for both analogue and category approaches. Oct-2 -ene is not antcipated to induce gene mutations or chromosome aberrations.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Additional information

Genetic Toxicity in Bacteria in vitro:

Information is available from one study that has investigated the in vitro bacterial genetic toxicity potential of 1-octene.

In this investigation (Glueck, 1983), tester strains TA98, TA100, TA1535, TA1537, and TA1538 of S. typhimurium were exposed to 1-octene (Neodene 8 Alpha Olefin) in ethanol at concentrations of 1.4 x 10-4, 4.5 x 10 -4, 1.4 x 10-3, 4.5 x 10-3, 1.4 x 10-2, 4.5 x 10-2, 0.14, 0.45 mg/plate in the presence and absence of mammalian metabolic activation using a pre-incubation method. In a preliminary cytotoxicity screen, effects were observed at 0.45 mg/plate in the absence of metabolic activation and at 4.5 and 0.45 mg/plate in the presence of metabolic activation. In the mutagenicity assay, toxicity occurred at 0.45, 0.14 and 0.045 mg/plate in the absence and presence of metabolic activation with all the bacterial strains tested. A positive response (>2.5 times the background) for the number of revertant mutant colonies was observed for all positive controls tested in the presence and absence of metabolic activation. There was no evidence of a concentration related positive response of induced mutant colonies over background for the test material at any concentration tested. 1-Octene was not mutagenic in the presence or absence of S9. 

Information is available from an in vitro bacterial genetic toxicity potential of 1-hexene

(Sawin, 1982), strains TA 98, TA 100, TA 1535, TA 1537, and TA 1538 of S. typhimurium were exposed to 1-hexene (Neodene 6) in ethanol at concentrations of 0.002; 0.005; 0.01; 0.02; 0.05; 0.1; 0.2; 0.5 mg/plate in the presence and absence of mammalian metabolic activation using the preincubation plate-incorporation method. Toxicity was observed in all tester strains at the 0.5 mg/plate dose level in the presence and absence of metabolic activation. No substantial increases in revertant colony numbers of any of the five tester strains were observed subsequent to treatment with 1-hexene at any dose level, either in the presence or absence of metabolic activation. There was no evidence of induced mutant colonies over background or a concentration related positive response observed during the study. The positive controls induced the appropriate responses in the corresponding strains. 

Information is available from one study that investigated the in vitro bacterial genetic toxicity potential of 1-dodecene.

In this study (Dean, 1980), five strains of S. typhimurium (TA98, TA100, TA1535, TA1537, and TA1538) and 2 strains of E. coli (WP2 and WP2uvrA) were exposed to 1-dodecene (alpha C12) in acetone at concentrations of 0, 0.2, 2, 20, 200, or 2000 ug/plate in the presence and absence of mammalian metabolic activation using a plate-incorporation method. No increase in reverse mutation rate was noted in either assay in the presence or absence of metabolic activation. A preliminary study to assess bacterial cytotoxicity to determine appropriate doses was not performed.

Information is available from one study that investigated the in vitro bacterial genetic toxicity potential of 1-octadecene.

In this investigation (Dean, 1980), five strains of S. typhimurium (TA98, TA100, TA1535, TA1537, and TA1538) and 2 strains of E. coli (WP2 and WP2uvrA) were exposed to 1- octadecene (alpha C18) in acetone at concentrations of 0, 0.2, 2, 20, 200, or 2000 ug/plate in the presence and absence of mammalian metabolic activation using a plate- incorporation method. No increase in reverse mutation rate was noted in either assay in the presence or absence of metabolic activation. A preliminary study to assess bacterial cytotoxicity to determine appropriate doses was not performed.

Genetic Toxicity in Mammalian Cells in vitro:

Cytogenicity in Mammalian Cells in vitro:

Information is available from one study that has investigated the in vitro mammalian cytogenicity potential of 1-octene.

In this test (Sawin and Smith, 1983) was designed to evaluate the potential for 1-octene (Neodene-8 alpha olefin) to induce chromosome aberrations in Chinese Hamster Ovary (CHO) cells. Following a preliminary cytotoxicity assay the main study was conducted by exposing the CHO cells to 6 concentrations of 1-octene prepared in ethanol; concentrations of the test chemical ranged from, 1.0 X 10-2mg/mL to 1.0X10 -3mg/mL in 1/5 log10dilutions. Cells were exposed both, in the presence and absence of S9 fractions. The study included appropriate negative and positive controls. Concentrations of 0.072 mg/mL 1-octene and above were cytotoxic to CHO cells. In the absence of S9 no increase in aberrations was

found. In the presence of S9, the mean aberrations per cell exceeded the solvent control by 2-fold or more at the 5 highest concentrations tested while the percent abnormal cells exceeded the solvent controls by 2 -fold or more at 3 nonconsecutive concentrations. The increases, however, were only slightly over 2-fold and were not concentration dependent. It was conclude that 1-octene was not clastogenic toward mammalian cells in vitro.

In a chromosome aberration test, Chinese Hamster Ovary cells (CHO) were exposed to 1-hexene (Neodene 6 alpha olefin) in ethanol at concentrations of 0, 0.034, 0.06, 0.11, 0.19, 0.34, or 0.60 mg/mL (Sawin and Smith, 1983) in the presence and absence of metabolic activation for 3 hours (+S9) or 12 hours (-S9). Two separate studies were performed. In the first study, the three highest doses in the absence of S9 were toxic; no increase in aberrations was noted in the remaining concentrations. In the presence of S9, the 0.6 mg/mL concentration was toxic and an increase in aberrations was observed in the 0.06 mg/mL concentration. Toxicity at the top two doses, +S9, was also noted in the second study, but no increase in aberrations was observed. Therefore, it was concluded that 1-hexene did not induce chromosomal aberrations in CHO cells under the conditions of this study. The positive control substances (triethelene amine and cyclophosphamide) induced the appropriate response. 

Information is available from one study that has investigated the in vitro mammalian cytogenicity potential of 1-dodecene.

In this investigation, monolayer slide cultures of rat liver cells (RL1) were exposed to 1-dodecene (alpha C12) in acetone at concentrations of 0, 125, 250, 500 ug/mL for 24 hours (Dean, 1980). The highest treatment level was cytotoxic. The positive control (DMBA) induced the appropriate response. There was no evidence of consistent increase in the frequency of chromosomal damage (chromatid gaps, chromatid breaks, or total chromosomal aberrations) induced over background.

Information is available from one study that has investigated the in vitro mammalian cytogenicity potential of 1-octadecene..

In this chromosomal aberration test, monolayer slide cultures of rat liver cells (RL1) were exposed to 1-octadecene (alpha C18) in acetone at concentrations of 0, 125, 250, 500 ug/mL for 24 hours (Dean, 1980). The highest treatment level was cytotoxic.. The positive control (DMBA) induced the appropriate response. There was no evidence of consistent increase in the frequency of chromosomal damage (chromatid gaps, chromatid breaks, or total chromosomal aberrations) induced over background.

Other Studies in vitro:

Additional information is available from other studies that have investigated the in vitro genotoxic potential of 1-octene.

1-Octene (Neodene 8 alpha olefin) diluted in ethanol was investigated using the BALB/3T3 cell transformation test (Rundell, 1983). Preliminary studies indicated that the test substance was cytotoxic to the cells so concentrations of 16, 32, 40, 50, and 62.5 ug/mL without S9, and 63, 125, 250, 500, and 1000 ug/mL in the presence of S9, were used for the transformation assay. 1-octene did not increase the transformation frequency of Balb/c-3T3 cells ± S9.

Additional information is available from other studies that have investigated the in vitro genotoxic potential of 1-hexene.

In one study (Goode, 1983), 1-hexene (Gulftene 6) was assessed using the BALB/3T3 cell transformation test. In a preliminary assay, cytotoxicity (measured as percent relative survival) in BALB/3T3 cells increased in a dose-dependent manner, with percent relative survival rates of 67.6%, 54.8%, 24.1%, and 4% at 1-hexene concentrations of 32, 1024, 2048, and 5000 ug/mL, respectively. In the main transformation assay, the relative cloning efficiency at the highest dose tested (2048 ug/mL) was 57.9% indicating toxicity to the BALB/3T3 cells. Raw transformation data for Type III foci was 3 for medium control; 4 for the vehicle control; 3 for 1-hexene at 256 ug/mL; 3 at 512 ug/mL; 1 at 1024 ug/mL; and 2 at 2048 ug/mL. The raw transformation data (Type III foci) for the positive control (3 -methylcholanthrene) was 27. Under the conditions of this BALB/3T3 transformation

assay, 1-hexene was negative for cell transformation.

Genetic Toxicity in vivo

Information is available from one study that investigated the in vivo genotoxic potential of 1-hexene in the mouse bone marrow micronucleus assay.

In this investigation (Harnois, 1983), 5 Crl:CDR-1 (ICR) BR Swiss mice/sex/dose were treated (whole body, inhalation exposure) with 1-hexene (Gulftene 6) at doses of 0; 1000; 10,000; or 25,000 parts per million for a period of 2 hours on two consecutive days. Bone marrow cells were harvested post sacrifice on either day 3 or 4 of the study period. Animals in the negative control group were exposed to clean, filtered air alone while animals in the positive control group were treated with 75 mg/kg cyclophosphamide by i.p.injection. Lethargy and rapid respiration were observed in animals treated at 10,000 and 25,000 parts per million but these clinical effects were reversible post- exposure. 50 percent of the female mice exhibited statistically lower mean body weights on days 1 and 3. However, mean body weights of the remaining female mice were observed to

be normal when compared to corresponding control animals. No significant increase in the frequency of micronucleated polychromatic erythrocytes in the bone marrow was noted after treatment at any dose level. Male and female animals induced with cyclophosphamide exhibited a statistically higher frequency of micronucleated polychromatic erythrocytes in the bone marrow when compared with negative controls.

Information is available from one study that has investigated the in vivo genetic toxicity potential of Alkenes, C20-24.

Justification for selection of genetic toxicity endpoint
Genotoxicity testing has been conducted on 12 members of this category ranging from C6 to C24-28. This includes 16 bacterial mutation asssays (covering C6 to C2428), one mammalian cell mutation test (C6), 9 mammalian cell cytogenetics assays (covering C6 to C20-24), 4 miscellaneous in vitro tests (UDS and cell transformation, covering C6 and C8) and 6 in vivo micronucleus assays (covering C6 to C20-24). These results of these studies demonstrate that higher olefins are not genotoxic in vitro or in vivo.

Short description of key information:
Not genotoxic in bacterial and mammalian cells in vitro or in mice following testing in vivo.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Genotoxicity testing has been conducted on 12 members of this category, ranging from C6 to C24 -28. This includes investigations performed using bacterial and mammalian cells in vitro together with testing in vivo. There was no evidence of mutagenicity or genotoxicity in any of these studies, and no classification is necessary according to the CLP regulation.

Read-across of these results to Oct-2 -ene is claimed as valid based on the justifications provided for both analogue and category approaches