1-Octanol, reaction products with epichlorohydrin and 2-mercaptoethanol

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

The test material did not induce any statistically significant, dose-related increases in the frequency of cells with structural or numerical chromosome aberrations either in the presence or absence of a liver enzyme metabolising system or after various exposure times. The test material was therefore considered to be non-clastogenic to CHL cells in vitro. The test material was considered to be non-mutagenic.

Link to relevant study records

Reference

Endpoint:

in vitro cytogenicity / chromosome aberration study in mammalian cells

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2006

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: according to EC Directive 92/69/EEC and Regulation EC/440/2008 guideline methods under GLP conditions

Qualifier:

according to guideline

Guideline:

OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)

GLP compliance:

yes

Type of assay:

in vitro mammalian chromosome aberration test

Species / strain / cell type:

Chinese hamster Ovary (CHO)

Test concentrations with justification for top dose:

Short Term Treatment Test - Experiment 1

Group Final Concentration of Test Material (µg/ml)
6(18)-hour without S9 0*, 10.31 ,20.63*, 41.25*, 82.5*, 123.75, 165, MMC 0.1 *
6(18)-hour with S9 0*, 20.63,41.25*, 82.5*, 165*, 247.5, 330, CP 5.0*


Continuous Treatment Test - Experiment 2 and Short Term

Group Final Concentration of Test Material (µg/ml)
24-hour 0*, 5.15, 10.31*, 20.63*, 30.94*, 41.25*, 82.5 MMC 0.05*
6(18)-hour with S9 0*, 10.31,20.63*, 41.25*, 82.5*, 165,247.5, CP 5.0*


* Dose levels selected for metaphase analysis
MMC = mitomycin C
CP = cyclophosphamide

Details on test system and experimental conditions:

The Chinese Hamster Lung (CHL, also known as CHL/IU) cell line, isolated by Koyama et al (1970) and cloned by Ishidate and Sofbni (1985), was used. The CHL cell line has an average generation time of approximately 17 hours when growing under normal experimental conditions.

Cells were grown in Eagle's Minimal Essential Medium (MEM) with HEPES buffer and Earle's Salts and supplemented "in-house" with 10% foetal bovine serum and antibiotics, at 37°C with 5% C02 in air.

Cultures were established 16 to 72 hours prior to treatment using the appropriate number of cells per flask depending on the pre-exposure culture period. The cells were exposed to at least three doses of the test material, vehicle and positive controls both with and without metabolic activation. All exposures were performed in duplicate (A + B) and cultures were maintained at 37°C in a humidified atmosphere of 5% C02 in air.

Statistics:

The frequency of cells with aberrations excluding gaps and the frequency of polyploid cells was compared, where necessary, with the concurrent vehicle control value using Fisher's Exact test.

Key result

Species / strain:

mammalian cell line, other: Chinese Hamster Lung (CHL, also known as CHL/IU)

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Positive controls validity:

valid

Conclusions:

Interpretation of results (migrated information):
negative

The test material did not induce any statistically significant, dose-related increases in the frequency of cells with structural or numerical chromosome aberrations either in the presence or absence of a liver enzyme metabolising system or after various exposure times. The test material was therefore considered to be non-clastogenic to CHL cells in vitro.

Executive summary:

The test material did not induce any statistically significant, dose-related increases in the frequency of cells with structural or numerical chromosome aberrations either in the presence or absence of a liver enzyme metabolising system or after various exposure times. The test material was therefore considered to be non-clastogenic to CHL cells in vitro.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Additional information

Additional information from genetic toxicity in vitro:

Justification for selection of genetic toxicity endpoint
Two tests available, one according to OECD 471 and one according to OECD 473. Both tests are done according to EC Directive 92/69/EEC and Regulation EC/440/2008 guideline methods under GLP conditions. Klimisch rating = 1. Both tests support each other. Hence it dose not matter, which test should be selected as the primary one.

Justification for classification or non-classification

According to the UN Globally Harmonized System of Classification and Labelling of Chemicals (GHS) Part 3 Chapter 3.5 this substance is not causing concern to be mutagenetic/genetic toxic.