Ethyl 4-[[(methylphenylamino)methylene]amino]benzoate

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian cell study: DNA damage and/or repair

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:
Ethyl 4-[[(methylphenylamino)methylene]amino]benzoate
-EC: 260-976-0
-CAS: 57834-33-0

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

- Available GLP studies: No GLP studies available for this substance for the end point ‘genetic toxicity in vivo’.
- Available non-GLP studies: No non-GLP study available for this substance for the end point ‘genetic toxicity in vivo’.
- Grouping and read-across: it has been attempted to look at similar substances, and although such substances exist, there is limited data on most of these. Several similar substances give negative results from in-vitro data and weight of evidence is that the substance for further examination will be negative.
Unfortunately, this has not been considered sufficient evidence to avoid further work, although if ECHA are aware of sufficient existing information on this class of substance to avoid this animal study, it would be good to be informed. Everlight are willing to use alternative sources of data to avoid new animal studies if such data exists.
- Historical human data: There is no historical human data available for this substance on ‘genetic toxicity in vivo’. Hence no evidence of human adverse effect.
- (Q)SAR: not available and not appropriate for this endpoint
- In vitro methods: The in vitro bacterial reverse mutation assay (OECD 471), in vitro mammalian chromosome aberration (OECD 473) and in vitro Mammalian Cell Gene Mutation Tests (OECD 490) were conducted. The present dossier contains positive results for the in vitro bacterial mutation assay OECD 471 which raises the concern for gene mutation. Therefore, in vivo mutagenicity test is inevitable.

- Weight of evidence: there is no alternative data available for weight of evidence approach using similar testing endpoints
- Substance-tailored exposure driven testing [if applicable]: this approach is not applicable for this substance. Exposure to human is unavoidable (still exist) during process.

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:

As indicated above, adaptation in accordance with Annex XI does not seem possible, but Everlight are willing to act on any proposals by ECHA to avoid the need for further animal testing.

CONSIDERATIONS ON THE IN VIVO STUDIES INSERTED IN THE DOSSIER:

-OECD 489 allows to measure DNA strand breaks, that may result from direct interactions with DNA, alkali labile sites or as a consequence of incomplete excision repair. Therefore, the alkaline comet assay recognises primary DNA damage that would lead to gene mutations and/or chromosome aberrations, but will also detect DNA damage that may be effectively repaired or lead to cell death. The comet assay can be applied to almost every tissue of an animal from which single cell or nuclei suspensions can be made, including specific site of contact tissues.

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 489 (In vivo Mammalian Alkaline Comet Assay)

Test material

Test material information

Constituent 1

Reference substance name:

Ethyl 4-[[(methylphenylamino)methylene]amino]benzoate

EC Number:

260-976-0

EC Name:

Ethyl 4-[[(methylphenylamino)methylene]amino]benzoate

Cas Number:

57834-33-0

Molecular formula:

C17H18N2O2

IUPAC Name:

ethyl 4-[[(methylphenylamino)methylene]amino]benzoate

Test material form:

liquid

Details on test material:

- Name of test material (as cited in study report): Eversorb EP4
- Substance type: Liquid
- Composition of test material, percentage of components: 98.94%
- Lot/batch No.: 4023
- Storage condition of test material: Ambient

Test animals

Species:

mouse