Registration Dossier

Diss Factsheets

Administrative data

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information
One bacterial reverse mutation study is available (HLS, 1996) which is a key study. This study showed a negative result both with and without metabolic activation. One mammalian cytogenicity study is available (HUNTINGDON LIFE SCIENCES, 1997) which is a key study. This study showed a negative result both with and without metabolic activation.
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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study run to a method comparable with current guidelines and to GLP.
Qualifier:
according to guideline
Guideline:
EU Method B.10 (Mutagenicity - In Vitro Mammalian Chromosome Aberration Test)
Deviations:
no
GLP compliance:
yes
Type of assay:
other: in vitro mammalian cytogenicity (B10)
Species / strain / cell type:
mammalian cell line, other: Human lymphocytes
Metabolic activation:
with and without
Metabolic activation system:
Aroclor-induced at liver S9
Test concentrations with justification for top dose:
Concentration range in the main test (with metabolic activation): 312.5 ... 2500 µg/ml
Concentration range in the main test (without metabolic activation): 156.3 ... 750 µg/ml
Vehicle / solvent:
dimethyl sulphoxide
Details on test system and experimental conditions:
Exposure period (with metabolic activation): 3 hours
Exposure period (without metabolic activation): 21 hours

Fixation time:
First test, without S-9 mix, 21 hour harvest

First test, with S-9 mix, 21 hour harvest

Second test, without S-9 mix, 21 and 45 hour harvest

Second test, with S-9 mix, 21 and 45 hour harvest
Species / strain:
mammalian cell line, other: Human lymphocytes
Metabolic activation:
with
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
> 2500 µg/ml
Species / strain:
mammalian cell line, other: Human lymphocytes
Metabolic activation:
without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
> 750 µg/ml
Remarks on result:
other: other: main test
Remarks:
Migrated from field 'Test system'.
Conclusions:
Interpretation of results (migrated information):
negative with metabolic activation
negative without metabolic activation

Under conditions of this study, the substance was found to be nonmutagenic (negative) in both with metabolic activation and without metabolic activation.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Additional information

Additional information from genetic toxicity in vitro:

One bacterial reverse mutation study and one mammalian cytogenicity study are available (HLS, 1996 & HLS, 1997 ) according to EU Method B.13/14 & EU Method B.10. All two studies are considered as reliable and both of them are key studies. All two studies gave negative results both with and without metabolic activation.


Justification for selection of genetic toxicity endpoint
The study in mammalian cells was chosen over that in bacterial cells, as the higher level study.

Justification for classification or non-classification

Genetic toxicity in vitro: Negative result.

Therefore in accordance with Regulation (EC) No. 1272/2008 Table 3.5.1 the substance is not classified for the genetic toxicity endpoint.