Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
Type of information:
experimental study planned
Study period:
after approval by ECHA
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: Aminofunctional alkoxysilanes/Reaction mass of tri-(methoxy/ethoxy)-methylsilane and amino-functional (methoxy/ethoxy)-silanes
- Name of the substance for which the testing proposal will be used [if different from tested substance]: Not applicable

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:

The following GLP-compliant in vitro studies have been considered prior to making the test proposal which is being addressed by this document:

Gene mutation (Bacterial reverse mutation assay / Ames test): negative with and without activation in Salmonella typhimurium strains TA 98, TA 100, TA 1535, TA 1537 and E.coli WP2 uvrA (OECD 471) (Donath, 2012).

In vitro cytogenicity in mammalian cells: positive with and without metabolic activation in Chinese hamster V79 cells (OECD 473) (Hofman-Huether, 2013)


- Available non-GLP studies:

No non-GLP studies are available.

- Historical human data:

No historical human data are available.

- (Q)SAR:

QSAR is not considered to be appropriate because there is no existing QSAR method which can confirm in vivo cytogenicity, which is the remaining uncertainty of the data set.

- In vitro methods:

The following in vitro methods have been considered prior to making test proposal which is being addressed by this document:

 OECD 471 – negative data available for registered substance
 OECD 473 – positive data available for registered substance

The available in vitro methods have therefore been considered as a part of the tiered approach.


- Weight of evidence:

There are no available data for a weight of evidence approach.

- Grouping and read-across

There are no suitable analogue substance that can be used for read-across.

- Substance-tailored exposure driven testing [if applicable]: Not applicable
- Approaches in addition to above [if applicable] : Not applicable
- Other reasons [if applicable]: Not applicable



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:

Annex VIII cites that appropriate in vivo mutagenicity studies shall be considered in the case of a positive result in any of the genotoxicity studies in Annex VII or VIII. Since a positive result for cytogenicity in mammalian cells (OECD 473) is reported, it needs to be established whether the effect is evident in vivo. Therefore, there are no specific adaptation possibilities.

FURTHER INFORMATION ON TESTING PROPOSAL IN ADDITION TO INFORMATION PROVIDED IN THE MATERIALS AND METHODS SECTION:
An in vivo mammalian erythrocyte micronucleus test by the oral route is proposed to be conducted after approval by ECHA, according to OECD Test Guideline 474 and in compliance with GLP.

Data source

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
Type of assay:
micronucleus assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid

Results and discussion

Applicant's summary and conclusion