Diamminediisocyanatozinc

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

experimental study planned

Justification for type of information:

TESTING PROPOSAL ON VERTEBRATE ANIMALS
As a general remark ahead, the registrant kindly asks ECHA to assess and decide about the testing proposal for an in vivo Comet assay, IUCLID chapter 7.6.2, first. The outcome of this Comet assay may influence the necessity to conduct this study.

NON-CONFIDENTIAL NAME OF SUBSTANCE:
- Name of the substance on which testing is proposed to be carried out: Diaminodiisocyanatozinc

CONSIDERATIONS THAT THE GENERAL ADAPTATION POSSIBILITIES OF ANNEX XI OF THE REACH REGULATION ARE NOT ADEQUATE TO GENERATE THE NECESSARY INFORMATION:
- Available GLP studies: None related to developmental toxicity (or reproductive toxicity)
- Available non-GLP studies: None related to developmental toxicity (or reproductive toxicity)
- Historical human data: Not available
- (Q)SAR: Not available
- In vitro methods: Not available
- Weight of evidence: No data available
- Grouping and read-across: No possible alternative structures available
- Substance-tailored exposure driven testing [if applicable]: n/a
- Approaches in addition to above [if applicable]: n/a
- Other reasons [if applicable]: As will be outlined below, the currently available information is not sufficient. However, by conducting a Comet assay ahead, for which a testing proposal was submitted, sufficient information may be gained to allow waiving according to REACH Annex IX column 2.

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:

Currently, the available data is not adequate to assess the potential developmental toxicity of the registered substance. There is neither a developmental toxicity study of any kind in any species available, nor human data, nor a reproductive/developmental toxicity screening study, nor QSAR estimations.

However, according to REACH Annex IX, the following is required:
Pre-natal developmental toxicity study, one species, most appropriate route of administration, having regard to the likely route of human exposure (B.31 of the Commission Regulation on test methods as specified in Article 13(3) or OECD 414), unless either:
— the substance is known to be a genotoxic carcinogen and appropriate risk management measures are implemented, or
— the substance is known to be a germ cell mutagen and appropriate risk management measures are implemented, or
— the substance is of low toxicological activity (no evidence of toxicity seen in any of the tests available), it can be proven from toxicokinetic data that no systemic absorption occurs via relevant routes of exposure (e.g. plasma/blood concentrations below detection limit using a sensitive method and absence of the substance and of metabolites of the substance in urine, bile or exhaled air) and there is no or no significant human exposure.

The registrant proposes in parallel to conduct an in vivo Comet Assay to assess the necessity for a possible classification as germ cell mutagen by combination of data from target tissues and toxicokinetik data based of the substances phys.-chem. parameters and available repeated dose toxicity data.

So, until ECHA has not decided about the need to conduct this Comet Assay and the possibly available results, it cannot be clearly decided whether or not the specific adaption possibilities of annexes VI to X are not adequate. Hence, the registrant kindly asks to postpone the decision about the present testing proposal until the above-mentioned information is available.

FURTHER INFORMATION ON TESTING PROPOSAL IN ADDITION TO INFORMATION PROVIDED IN THE MATERIALS AND METHODS SECTION:
- Details on study design / methodology proposed: none additional

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 414 (Prenatal Developmental Toxicity Study)

Test material

Test material information

Constituent 1

Reference substance name:

Diamminediisocyanatozinc

EC Number:

401-610-3

EC Name:

Diamminediisocyanatozinc

Cas Number:

122012-52-6

Molecular formula:

C2H6N4O2Zn

IUPAC Name:

copper(2+) bis(carbonylazanide) diamine

Test animals

Species:

rat