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Administrative data

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information
In summary, the test substance 6,6'-di-tert-butyl-2,2'-methylenedi-p-cresol reveals no genotoxic activities in vitro.
Link to relevant study records
Reference
Endpoint:
in vitro gene mutation study in mammalian cells
Remarks:
Type of genotoxicity: gene mutation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP and guideline study
Qualifier:
according to
Guideline:
OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Type of assay:
mammalian cell gene mutation assay
Target gene:
hprt locus
Species / strain / cell type:
Chinese hamster lung fibroblasts (V79)
Metabolic activation:
with and without
Metabolic activation system:
S9 mix, S9 from phenobarbital/beta-naphthoflavone induced male Wistar rat livers
Test concentrations with justification for top dose:
pre-tests (2nd, 3rd): -S9 short-term treatment: 0.001 to 3.0 µg/ml, -S9: long-term treatment: 0.16 to 30.0 µg/ml, +S9 short-term treatment: 0.5 to 30 µg/ml; concentrations used for mutation rate analysis: -S9 short-term treatment: 0.094 to 1.5 µg/ml, -S9 long-term treatment: 1.0 to 8.0 µg/ml, +S9 short-term treatment: 12.5 to 22.5 µg/ml
Untreated negative controls:
not specified
Negative solvent / vehicle controls:
yes
True negative controls:
not specified
Positive controls:
yes
Positive control substance:
other: -S9: ethylmethanesulphonate, +S9: 7,12-dimethylbenzanthracene
Species / strain:
Chinese hamster lung fibroblasts (V79)
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
not specified
Positive controls validity:
valid
Remarks on result:
other: strain/cell type: Chinese hamster lung fibroblasts (V79)
Remarks:
Migrated from field 'Test system'.

No substantial and reproducible dose dependent increase of the mutation frequency was observed in both main experiments.

The author stated that the test substance did not induce gene mutations at the HPRT locus in V79 cells under the experimental conditions used.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Additional information

Additional information from genetic toxicity in vitro:

In vitro data

The test substance 6,6’-di-tert-butyl-2,2’-methylendi-p-cresol (DBMC) was evaluated in several bacterial mutation assays, mainly in the Ames assay. In a GLP study, which was conducted in accordance with OECD Guideline 471, no mutagenic effects were found up to the highest concentration evaluated with and without metabolic activation. In addition no toxicity of the test substance was detected up to 5000 µg/plate (MHWJ 1996).

The non-mutagenic potential of 6,6’-di-tert-butyl-2,2’-methylendi-p-cresol (DBMC) was confirmed in HPRT mutation assay with V79 cells (Harlan 2010). No substantial and reproducible dose dependent increase of mutant frequency was observed in both main experiments.

No genotoxic effects were found in an in vitro chromosomal aberration assay with CHL/IU cells. This GLP study was conducted in accordance with OECD Guideline 473 (MHWJ 1996). A continuous treatment was done with concentrations of 0, 0.002, 0.004 and 0.008 mg/ml without metabolic activation. The short-term treatment was conducted with and without metabolic activation, with concentrations of 0, 0.0005, 0.001, 0.002 mg/ml (without metabolic activation) and 0, 0.0075, 0.015, 0.03 mg/ml (with metabolic activation). Cytotoxicity of the test substance, indicated by a 50% growth inhibition, was noted at the highest dose groups evaluated with and without metabolic activation. No genotoxic effects were noted in any of the dose groups evaluated neither with nor without metabolic activation.

Justification for classification or non-classification

Classification is not required based on the classification criteria 67/548/EWG and regulation no. 1272/2008 (GHS).