Registration Dossier

Administrative data

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
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: OO-tert-butyl monoperoxymaleate (CAS 1931-62-0)

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 potential of OO-tert-butyl monoperoxymaleate to induce genotoxic effects was tested in a suitable in vitro test battery, conducted under GLP. The target substance was tested negative in a bacterial reverse gene mutation test conducted according to OECD 471 and in a mammalian cell HPRT mutation assay according to OECD 476. In an in vitro micronucleus test in Chinese hamster V79 cells (OECD 487), OO-tert-butyl monoperoxymaleate did induce structural and/or numerical chromosomal damage.

- Available non-GLP studies:
There are no non-GLP studies available to address this potential mode of action.

- Historical human data:
There is no historical human data available to address this potential mode of action.

- (Q)SAR:
The use of QSARs models for the prediction of genotoxicity is a possibility to address this endpoint. However, the outcome of a QSAR assessment will not overrule the positive results of an in vitro micronucleus test.

- In vitro methods:
Further in vitro testing is not considered sufficient to provide information to conclude on this endpoint.

- Weight of evidence:
There is no additional relevant information available that can be used in a WoE to cover this endpoint for registration and classification purposes. Experiments with other members of the chemical group of peroxyester indicate that this functionality might lead to false positive results in in vitro tests. However, false positive results do not occur in all members of the group, and this mode of action would not account for the non-peroxide part of the molecule and/or degradation products.

- Grouping and read-across:
No further experimental data on potential analogues are available.

- Substance-tailored exposure driven testing [if applicable]:
The uses of this substance do not allow to use substance tailored exposure driven arguments to avoid the requirement for this study.

- Approaches in addition to above:
Not applicable

- Other reasons [if applicable]:
No data is available that would allow a general adaptation possibility as identified in Annex XI of the REACH Regulation. More specific, no in vivo data is available which would allow to draw a conclusion on the classification of the substance.

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:

- In accordance to ANNEX IX of the REACH Regulation 1907/2006, column 2 of standard information requirement 8.4: "If there is a positive result in any of the in vitro genotoxicity studies in Annex VII or VIII and there are no results available from an in vivo study already, an appropriate in vivo somatic cell genotoxicity study shall be proposed by the registrant". Based on the positive results from the in vitro micronucleus test (OECD 487, GLP, IUCLID section 7.6.1, Donath (2017)) and as no additional in vivo data is available, it is necessary to propose an appropriate in vivo somatic cell genotoxicity test (OECD 474).

FURTHER INFORMATION ON TESTING PROPOSAL IN ADDITION TO INFORMATION PROVIDED IN THE MATERIALS AND METHODS SECTION:

- Details on study design / methodology proposed [if relevant]: To assess if the induction of micronuclei on V79 cells in vitro is also prominent in vivo, it is proposed to conduct an in vivo micronucleus test in accordance to OECD TG 474 (Mammalian Erythrocyte Micronucleus Test). This study will be contracted and conducted at a GLP certified laboratory.

Data source

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
Deviations:
no
GLP compliance:
yes
Type of assay:
mammalian erythrocyte micronucleus test

Test material

Reference
Name:
Unnamed
Type:
Constituent

Results and discussion

Applicant's summary and conclusion