Diamminediisocyanatozinc

Toxicity to reproduction

Administrative data

Endpoint:

screening for reproductive / developmental toxicity

Data waiving:

other justification

Justification for data waiving:

other:

Justification for type of information:

JUSTIFICATION FOR DATA WAIVING
According to REACH Annex VIII column 2, this study does not need to be conducted if:
— 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
— relevant human exposure can be excluded in accordance with Annex XI section 3, or
— a pre-natal developmental toxicity study (Annex IX, 8.7.2) or, either an Extended One-Generation Reproductive Toxicity Study (B.56, OECD TG 443) (Annex IX, section 8.7.3) or a two-generation study (B.35, OECD TG 416), is available.

There are currently two testing proposals, one dependent on the other one, submitted in the dossier. To be more precise, a testing proposal for a comet assay is submitted. In case that all available genotoxicity tests including the comet assay, if approved, and toxicokinetic considerations do indicate the need to classify the substance as germ cell mutagen is required, no additional tests for reproductive toxicity incl. an OECD 421 or 421 studies are required.
If there is no classification as germ cell mutagen is required, the need for the conduction of an OECD 414 study, as described in the second study proposal, must be evaluated by ECHA. In case ECHA deems the conduction necessary, the last waving criterion for this reproductive toxicity screening study applies: This study does not need to be conducted if a pre-natal developmental toxicity study (Annex IX, 8.7.2) is available.
Hence, the necessity to perform this study is dependent on the decisions on and results of two preceding testing proposals, and so the data requirements of this registration are currently considered fulfilled.

Cross-reference

Reason / purpose for cross-reference:

other: testing proposal

Reference

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

Qualifier:

according to guideline

Guideline:

OECD Guideline 414 (Prenatal Developmental Toxicity Study)

Species:

rat