Formaldehyde, reaction products with m-phenylenediamine, sodium sulfide (Na2S) and sulfur

Genetic toxicity: in vivo

Administrative data

Endpoint:

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

Type of information:

experimental study planned

Study period:

The study period will be determined dependent 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: Formaldehyde, reaction products with m-phenylenediamine, sodium sulfide (Na2S) and sulfur, CAS 70892-34-1, EC / 274-986-8)


CONSIDERATIONS THAT THE GENERAL ADAPTATION POSSIBILITIES OF ANNEX XI 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).

- Historical human/control data: There are no historical human/control data 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 cannot be used to cover the in vivo genotoxicity endpoint alone but only as supporting information.

- In vitro methods: Since positive results were obtained in in vitro tests, an appropriate in vivo test is triggered according to the REACH regulation. There are no in vitro methods available which could replace the proposed in vivo test to clarify the endpoint genetic toxicity in vivo (gene mutation). For further information on the available in vitro results, please see below "Considerations that the specific adaptations possibilities of Annexes VI to IX (and column 2 thereof) of the REACH Regulation are not adequate to generate the necessary information".

- Weight of evidence: There is no information available that can be used in a weight of evidence approach 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).

- Substance-tailored exposure driven testing: not applicable
- Approaches in addition to above: not applicable
- Other reasons: 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:

The substance is fully registered according to REACH Annex VIII. Experimental in vitro genetic toxicity studies are available according to the standard information requirements of REACH Annex VII and VIII. Two studies (in vitro gene mutation studies in bacteria according to OECD 471) led to positive results. In these 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, TA98 and TA1535 - with metabolic activation. The result was reproducible. Therefore, the substance was considered mutagenic in these studies.
There are no results available from an in vivo genetic toxicity study already.
In line with Annex VIII, 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 under EU REACH to address the data gap in the study requirements.
The study will be commissioned as soon as a final decision is available.

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:

Formaldehyde, reaction products with m-phenylenediamine, sodium sulfide (Na2S) and sulfur

EC Number:

274-986-8

EC Name:

Formaldehyde, reaction products with m-phenylenediamine, sodium sulfide (Na2S) and sulfur

Cas Number:

70892-34-1

Molecular formula:

not applicable

IUPAC Name:

Formaldehyde, reaction products with m-phenylenediamine, sodium sulfide (Na2S) and sulfur

Test material form:

other: solution

Test animals

Species:

rat