Cyclododeca-1,5,9-triene

Endpoint summary

Additional information

In vitro Bacterial reverse mutation studies :

In the first study, The test substance was evaluated for mutagenic activity with and without exogenous metabolic (S9) activation. Three replicates were plated for each tester strain, test concentration, and condition. Dimethyl sulfoxide (DMSO) was used as the solvent and negative control. Four Salmonella typhimurium strains (TA97a, TA98, TA100, TA1535) and E. coli strain WP2 uvrA (pKM101) were used in this test, and the tested concentrations were 0; 10; 50; 100; 500; 1000; 2500; 5000 ug/plate.

There was no evidence of mutagenic activity was detected with or without metabolic activation in this Ames Test.

In the second study, the test substance cyclododecatriene 1,5,9 proved to be non-mutagenic under the conditions of this Ames test, both in the presence and in the absence of Aroclor-induced liver microsomes for all the test strains of Salmonella typhimurium (TA 1535, TA 1537, TA 1538, TA 98, TA 100) even in addition of 5,000 µg of test substance per plate and when the pre-incubation test was used. No data of cytoxicity were available. Therefore the results of this test are negative.

In vitro mammalian cells chromosomal aberration test :

The test substance was evaluated for clastogenic (chromosome-damaging) activity in human lymphocytes in vitro following 3- hour treatments with and without exogenous metabolic (S9) activation. The solvent (negative control) was acetone.

In the cytotoxicity assessment, both with and without activation, the mitotic index (MI) was decreased in a concentration dependent

manner. At 5 mg/mL, slides were unscorable in both sexes without activation, and MI was decreased to 26% of the negative control with activation. At 1 mg/mL, the MI was reduced to 38% of the negative control without metabolic activation, and 52% of the negative control with activation. In the activated system, at 5 mg/mL, AGT was increased to approximately 23 hours as compared to 15 hours in negative controls. At 1 mg/mL, AGT was increased 18-19 hours with activation. Significant increases in AGT were not observed in the non-activated system. Moderate cytotoxicity, as measured by a decrease in the MI, was observed with and without activation in Trial 1. The MI was reduced to 43% and 41% of the negative control in non-activated and activated systems, respectively, at 2.5 mg/mL in Trial 1. In Trial 2, the MI was reduced to 30% and 48% of the negative control in the non-activated and activated systems, respectively, at 5 mg/mL. No statistically significant increases in percent cells with structural chromosome aberrations were observed at any concentration tested. No dose-related increases in the percent of abnormal cells were observed in either activated or non-activated trials. There was no statistical increase in the percent of abnormal cells in the supplemental harvests. 1,5,9-Cyclododecatriene was not clastogenic in this assay.

In vivo micronucleus test :

Male rats were exposed nose-only to the test substance or negative control, respectively, for 6 hours per day for 2 consecutive days. Body weights and clinical signs were recorded. During exposure, all rats were observed for clinical signs of toxicity and for their reaction to an alerting stimulus. Immediately after sacrifice, marrow from 1 femur of each rat was collected. At least 3 slides per rat were prepared, fixed, and stained with acridine orange. Representative slides from each rat were examined blindly. Two thousand PCEs (polychromatic erythrocytes) per rat were evaluated for micronuclei. There was no test substance-induced mortality during the study. Statistically significant body weight losses were observed in the test substance-treated and the positive indicator rats. No clinical signs of toxicity were evident in rats during exposure. Rats in the treatment group did, however, display responses to an alerting stimulus ranging from diminished to none. Test substance-related clinical signs observed in the treatment group after exposure included lethargy and/or irregula r respiration, and likely represent manifestations of systemic toxicity.

There were no statistically significant increases in the MNPCE frequency in rats exposed to 1,5,9-cyclododecatriene. As expected, a statistically significant increase in MNPCE frequency was found in CP-treated rats. Additionally, no statistically significant depressions in the proportion of PCEs among 1000 erythrocytes were observed in rats exposed to the test substance. Under these experimental conditions, 1,5,9-cyclododecatreiene was considered as not genotoxic.

Short description of key information:
Several in vitro Bacterial reverse mutation studies are available and showed no evidence of mutagenic activity with and without metabolic activation. The test substance was evaluated for clastogenic (chromosome-damaging) activity in human lymphocytes in vitro and the results of this study are negative with and without metabolic activation.
An in vivo micronucleus study is available : 1,5,9-cyclododecatriene was tested by inhalation on rats, and results are negative at 500 ppm (3300 mg/m3).

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Proposed self-classification

- Regulation (EC) No 1272/2008

Not classified

- Directive 67/548/EEC

Not classified