N,N,N',N'-tetramethyl-2,2'-oxybis(ethylamine)

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Six in vitro genetic toxicity studies were performed with the test substance (2 Ames, 1 DNA Damage/Repair and 3 Gene Mutation studies). Five out of six in vitro tests were negative (one being equivocal).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Description of key information

Two in vivo mouse micronucleus studies were performed with the test substance. Both in vivo studies reported negative results.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Additional information

Genetic toxicity - in vitro:

Six in vitro genetic studies are performed with the test substance. In 5 out of 6 in vitro tests, the test substance was demonstrated as not mutagenic. In one in vitro test, the result was equivocal.

1. In a study conducted equivalent to OECD Guideline 476 (In vitro Mammalian Cell Gene Mutation Test), the test substance did not produce any statistically significant increases in the frequency of mutations of CHO cells at concentrations between 0.08 to 0.25% (by volume) in tests without an S9 metabolic activation system. With S9 activation, two tests, with either a similar or narrower range of concentrations as tested without S9, produced no indication of a dose-related, statistically significant effect of the treatments. The test substance was not active in producing gene mutations in CHO cells in these studies.

2. In a study conducted equivalent to OECD Guideline 479 (Genetic Toxicology: In Vitro Sister Chromatid Exchange Assay in Mammalian Cells), the test substance produced statistically significant effects upon the frequency of SCE over the range of concentrations tested with and without addition of an active S9 metabolic activation system. Although no apparent dose-related effects of exposure on the SCE frequency were evident, the test agent was considered weakly active based upon the statistical differences. Because of the very small increases observed, the effects may have been caused by contaminants in the sample. The result was reported to be a positive, but equivocal, indication of an effect of exposure to the test agent.

3. In a study conducted equivalent to OECD Guideline 482 (Genetic Toxicology: DNA Damage and Repair, Unscheduled DNA Synthesis in Mammalian Cells In Vitro), the test substance did not stimulate a reproducible, significant increase in the incorporation of radioactive thymidine in cells treated over a 500-fold range of test concentrations. The test substance was considered inactive this study with the hepatocyte test system.

4. In a study conducted equivalent to OECD Guideline 471 (Bacterial Reverse Mutation Assay), the test substance did not produce a dose-dependent mutagenic response in any of the Salmonella typhimurium strains. Under the conditions of this assay, the test substance was not mutagenic at 0.003, 0.01, 0.03, 0.1, and 0.3 uL/plate in the Salmonella/microsome mutagenicity assay.

5. In a study conducted according to OECD Guideline 482 (Genetic Toxicology: DNA Damage and Repair, Unscheduled DNA Synthesis in Mammalian Cells In Vitro), a negative result was reported based on the inability of the test substance to produce a mean nuclear grain count five or greater than the vehicle control mean nuclear grain count at any level of concentration.

6. The results of an Ames Assay on the test substance (conducted according to OECD Guideline 471 -Bacterial Reverse Mutation Assay) were negative in strains TA1535, TA1537, TA1538, TA98 and TA100 of Salmonella typhimurium both with and without metabolic activation preparation at 50, 166, 500, 1666 and 5000 µg/plate.

Genetic toxicity - in vivo:

1. In a study conducted equivalent to OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test), the test substance did not produce significant, treatment-related increases in the incidence of micronucleated polychromatophilic erythrocytes among male or female Swiss-Webster mice assessed at concentrations of 45, 90, or 145 mg/kg did not produce significant, treatment-related increases in the incidence of micronucleated polychromatophilic erythrocytes among male or female Swiss-Webster mice assessed at 30, 48, or 72 hours after treatment with a single dose by intraperitoneal injection. Therefore, the test substance was not considered to be an inducer of micronuclei in male or female Swiss-Webster mice under the conditions of this in vivo assay

2. In a study conducted equivalent to OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test), the test substance, administered in a single intraperitoneal dose at 100 mg/kg bw, was considered negative in the micronucleus test at the time intervals evaluated under the experimental condition of this assay. The findings were based on the inability of the test substance to produce a statistically significant increase in the incidence of micronuclei per 1000 PCE per animal in the treated group versus the negative control group under the conditions of this assay.

Justification for classification or non-classification

Based on the available data, the test substance is not a mutagen or genotoxic and is not to be classified as such according to the CLP Regulation 1272/2008.