Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
in vivo mammalian somatic cell study: gene mutation
Type of information:
experimental study planned
Study period:
The study will be performed in 2021 or in the following years depending on the ECHA decision.
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: Incozol 4 (bis[2-[2-(1-methylethyl)-3-oxazolidinyl]ethyl] hexan-1,2-diylbiscarbamate, CAS 59719-67-4, EC 261-879-6)


CONSIDERATIONS THAT THE GENERAL ADAPTATION POSSIBILITIES OF ANNEX IX OF THE REACH REGULATION ARE NOT ADEQUATE TO GENERATE THE NECESSARY INFORMATION:

- Available GLP studies: There are no GLP studies available for this substance covering the endpoint genetic toxicity in vivo (gene mutation).
- Available non-GLP studies: There are no non-GLP studies available for this substance covering the endpoint genetic toxicity in vivo (gene mutation).
- (Q)SAR: QSAR approaches for in vivo genotoxicity can be used as additional information in weight of evidence- or read across approaches or to assist in developing testing strategies. (ECHA Guidance on Information Requirements and Chemical Safety Assessment Chapter R 7a: Endpoint specific guidance, 2017). QSAR predictions can not be used to cover the in vivo genotoxicity endpoint alone but only as supporting information.
- Weight of evidence: There is no weight of evidence information available to cover the endpoint genetic toxicity in vivo (gene mutation).
- Grouping and read-across: There are no substances which apply for read-across addressing genetic toxicity in vivo (gene mutation).


CONSIDERATIONS THAT THE SPECIFIC ADAPTATION POSSIBILITIES OF ANNEXES VI TO IX (AND COLUMN 2 THEREOF) OF THE REACH REGULATION ARE NOT ADEQUATE TO GENERATE THE NECESSARY INFORMATION:

The substance is fully registered according to REACH Annex IX. Experimental in vitro genetic toxicity studies are available according to the standard information requirements of REACH Annex VII and VIII. One of these studies (in vitro gene mutation study in bacteria conducted by the General Testing Research Institute of Japan Oilstuff Inspectors' Corporation, Study no. B090953, Report no. AK09-21-0128, year: 2009) led to a positive result. In this Ames test, the number of revertant colonies induced by the test substance was more than twice of that of the corresponding negative (solvent) control for Salmonella typhimurium TA100 and Escherichia coli WP2uvrA- without metabolic activation, and for Salmonella typhimurium TA100 with metabolic activation. The result was reproducible. Therefore, the substance was considered mutagenic in this study.
There are no results available from an in vivo genetic toxicity study already. In line with Annex IX, column 2 of the REACH regulation, the registrant therefore proposes an in vivo somatic cell genotoxicity study.


FURTHER INFORMATION ON TESTING PROPOSAL IN ADDITION TO INFORMATION PROVIDED IN THE MATERIALS AND METHODS SECTION:

The Registrant is willing to conduct an in vivo mutagenicity study, i. e. in vivo mammalian alkaline comet assay according to OECD TG 489 in the rat via oral gavage administration. The current testing proposal will be submitted both under EU REACH and UK REACH to adress the data gap in the study requirements.
The study will be commissioned as soon as a final desicion is available.

Data source

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 489 (In vivo Mammalian Alkaline Comet Assay)

Test material

Constituent 1
Chemical structure
Reference substance name:
Bis[2-[2-(1-methylethyl)-3-oxazolidinyl]ethyl] hexan-1,2-diylbiscarbamate
EC Number:
261-879-6
EC Name:
Bis[2-[2-(1-methylethyl)-3-oxazolidinyl]ethyl] hexan-1,2-diylbiscarbamate
Cas Number:
59719-67-4
Molecular formula:
C24H46N4O6
IUPAC Name:
bis[2-[2-(1-methylethyl)-3-oxazolidinyl]ethyl] hexan-1,2-diylbiscarbamate

Results and discussion

Applicant's summary and conclusion