1,1,1,2,2,3,4,5,5,5-decafluoro-3-methoxy-4-(trifluoromethyl)pentane

Endpoint summary

Additional information

The mutagenic activity of the test article was evaluated in the Salmonella typhimurium reverse mutation assay (strains: TA1535, TA1537, TA98 and TA100, histidine-requiring) and the Escherichia coli reverse mutation assay (strain: WP2uvrA, tryptophan-requiring) in the presence and absence of a metabolic activation system (S9-mix: rat liver S9-mix induced by a combination of phenobarbital and ß naphthoflavone). The study was conducted in compliance with OECD GLP regulations (1997). The test method was based on OECD 471 (1997). The test material was dissolved in ethanol (vehicle). A combined rangefinding test/first mutation assay was conducted in all strains with concentrations up to 5000 ug/plate in the presence and absence of S-9 mix. The test article precipitated on the plates at the 5000 ug/plate dose level. The bacterial background lawn was not reduced at any of the concentrations tested and no biologically relevant decrease in the number of revertants was observed. In the second mutation assay the test article was tested up to concentrations of 5000 ug/plate in the presence and absence of S-9 mix. The test article precipitated at the highest dose level. The bacterial background lawn was not reduced at any of the concentrations tested and no decrease in the number of revertant colonies was observed. The test article did not induce a dose-related increase in the number of revertant colonies in any of the tester strains in the presence or absence of metabolic activation. Based on the results of the study, the test article is not mutagenic in the bacterial reverse mutation assay.

 

The chromosome aberration potential of the test article was evaluated in human blood peripheral lymphocytes in the presence and absence of metabolic activation (S9-mix: Phenobarbital and B-napthoflavone induced rat liver). The study was performed in compliance with OECD GLP (1997). The test method was based on OECD 473 (1997) and EEC Directive 2000/32/EC, Part B: Methods for the Determination of Toxicity; B.10 (2000). The MTDID test material was prepared in ethanol prior to administration. The assay was performed in two independent experiments. In the first assay, cells were tested up to a test article dose of 333 ug/mL for a 3-hour exposure with a 24-hour fixation time in the presence and absence of S9 mix. In the second assay, the cells were tested to up to 333 ug/mL test article dose for a 24-hour continuous exposure with a 24-hour fixation time and up to a 333 ug/mL dose for a 48-hour exposure with a 48-hour fixation time in the absence of S9-mix. The test article was also tested at a 333 ug/mL dose for a 3-hour exposure with a 48-hour fixation time in the presence of S9-mix. All dose levels were performed in duplicate and positive and negative controls were tested in parallel. The test article did not induce a statistically significant or biologically relevant increase in the number of cells with chromosome aberrations in two independent experiments. Based on the results of the study, the test article is not clastogenic in human lymphocytes in the presence or absence of metabolic activation.

The test substance MTDID 665 was evaluated for its clastogenic potential in the micronucleus assay in male Sprague Dawley rats. The study was conducted according to OECD 474 in compliance with OECD GLP. Test substance formulations were administered once per day for two consecutive days at a dose volume based on body weights via oral gavage. No vehicle control was used in the study; animals in Group 1 in the definitive assay were untreated. In the dose range-finding assay (DRF), the dose levels tested were 1500 and 2000 mg/kg (dose volume 0.91 and 1.21 mL/kg, respectively) in 3 animals/sex. Based upon the results, the high dose for the definitive assay was 2000 mg/kg, which is the guideline recommended limit dose. The definitive dose levels were 500, 1000, and 2000 mg/kg/ (dose volume 0.30, 0.60 and 1.21 mg/kg respectively). There were significant increases in the incidence of micronuclei in the test substance dosed animals as compared to the untreated control in the mid and high dose levels (1000 and 2000 mg/kg/day), however, as these values are within the 95% control limit of the historical control data, they are considered to not be of biological significance. Positive and untreated control values were within the expected range and there was a statistically significant increase in micronuclei in the positive control group as compared to the vehicle control. All criteria for a valid assay were met. Under the conditions of this study, the administration of MTDID 665 at dose levels up to and including a dose level of 2000 mg/kg was concluded to be negative in the micronucleus assay.

The mutagenic potential of the test article (structural analog HFE-7500 (source substance)) was evaluated in the L5178Y/TK+/- Mouse Lymphoma Mutagenesis assay in either the presence or absence of metabolic activation (S9-mix: Aroclor 1254). This study was performed in compliance with OECD GLP. The study design was based on OECD 476, and EC Directive 2000/32/EC B.17. The test article was prepared in acetone (vehicle). In the mutagenesis assay, the test article administered to the cells at concentrations of 0.4, 4.1, 41.4, 414, or 4140 ug/mL in each assay. One assay was performed in the presence or absence of S9-mix for a 4 hour exposure with a confirmatory assay in the presence of S9-mix and a 4 hour exposure. The fourth assay was performed in the absence of S9-mix for a 24 hour exposure. Appropriate positive and negative controls were run concurrently. No test article-treated cultures exhibited mutant frequencies that were at least 126 mutants per million clonable cells over the vehicle control in any culture in either the presence or absence of metabolic activation. Also, there was no concentration-related increase in mutant frequency. No evidence of toxicity was observed in any of the cultures. The results from the positive controls and negative control indicated that the test was valid both with and without metabolic activation. Based on the results of this study, the test article was not mutagenic in either the presence or absence of S9 activation in the L5178Y/TK+/- Mouse Lymphoma Mutagenesis Assay

Short description of key information:
In vitro and in vivo genetic toxicity studies have been conducted on HFE-7300 and a structural analog, HFE-7500. The results of the studies are:

Bacterial Reverse Mutation Assay: Negative when tested according to OECD 471.

Chromosome Aberration: Negative when tested according to OECD 473.

Rat Micronucleus Assay: Negative when tested according to OECD 474.

Mouse Lymphoma Assay: Negative when tested according to OECD 476 (Conducted on Structural Analog HFE-7500).

Endpoint Conclusion:

Criteria for classifying the test article as mutagenic are not met.

Justification for classification or non-classification

Criteria for classifying the test article as mutagenic are not met.