Registration Dossier

Administrative data

Endpoint:
in vivo mammalian somatic cell study: gene mutation
Type of information:
experimental study planned
Justification for type of information:
TESTING PROPOSAL ON VERTEBRATE ANIMALS

NON-CONFIDENTIAL NAME OF SUBSTANCE:
- Name of the substance on which testing is proposed to be carried out
3,4-dihydroxybenzonitrile
CONSIDERATIONS THAT THE GENERAL ADAPTATION POSSIBILITIES OF ANNEX XI OF THE REACH REGULATION ARE NOT ADEQUATE TO GENERATE THE NECESSARY INFORMATION [please address all points below]:
- Available GLP studies
Charles River (2017) Test report 515458. Evaluation of the Mutagenic Activity of CH02906 in the Salmonella typhimurium Reverse Mutation Assay and the Escherichia coli Reverse Mutation Assay (Plate Incorporation and Pre-Incubation Methods). According to OECD 471, GLP-compliant. Negative with and without mammalian metabolic activation system (S9).
Charles River (2017) Test report 515459. An in vitro Micronucleus Assay with CH02906 in Cultured Peripheral Human Lymphocytes. According to OECD 487, GLP-compliant. Negative with and without mammalian metabolic activation system (S9).
Charles River (2017) Test report 515460. Evaluation of the Mutagenic Activity of CH02906 in an in vitro Mammalian Cell Gene Mutation Test with L5178Y Mouse Lymphoma Cells. According to OECD 490, GLP-compliant. Positive for gene mutagenicity, positive result only observed without mammalian metabolic activation system (S9).
No substance-specific in vivo genotoxicity studies were identified.
- Available non-GLP studies: No non-GLP studies are available for this substance.
- Historical human data: No historical human data have been identified for this substance.
- (Q)SAR: The applicability of QSARs for higher tier mutagenicity endpoints is limited and therefore QSAR results are of limited use.
- In vitro methods
The available in vitro methods have been considered as part of the tiered approach to testing (see “List of substance-specific available GLP and non-GLP studies considered for this test proposal” above for details).
- Weight of evidence
3,4-dihydroxybenzonitrile was tested in three in-vitro mutagenicity tests, following the testing strategy proposed by ECHA (ECHA, 2017). Both the gene mutation test in bacteria (OECD 471) and the in-vitro micronucleus test (OECD 487) showed no indication of mutagenicity. However, the final test of the standard testing strategy, the mouse lymphoma assay (TK locus, OECD 490) resulted in evidence for gene mutations. No in vivo genotoxicity studies were identified for this or related substances. Following the ECHA testing strategy, an in vivo test is now required to conclude on the mutagenicity of this substance.
- Grouping and read-across: No read-across data were identified

CONSIDERATIONS THAT THE SPECIFIC ADAPTATION POSSIBILITIES OF ANNEXES VI TO X (AND COLUMN 2 THEREOF) OF THE REACH REGULATION ARE NOT ADEQUATE TO GENERATE THE NECESSARY INFORMATION:
Waiving according to column 2 does not apply.

FURTHER INFORMATION ON TESTING PROPOSAL IN ADDITION TO INFORMATION PROVIDED IN THE MATERIALS AND METHODS SECTION:
Details on study design / methodology proposed
An alkaline comet assay (OECD Test Guideline 489) is proposed as follow-up in vivo test.

Data source

Materials and methods

Results and discussion

Applicant's summary and conclusion