Registration Dossier

Administrative data

Endpoint:
in vivo mammalian cell study: DNA damage and/or repair
Type of information:
experimental study planned
Study period:
Within 2 years after ECHA consent
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: Reaction products of 2-hydroxyethyl methacrylate and diphosphorus pentaoxide (POEMA)
CONSIDERATIONS THAT THE GENERAL ADAPTATION POSSIBILITIES OF ANNEX XI OF THE REACH REGULATION ARE NOT ADEQUATE TO GENERATE THE NECESSARY INFORMATION:
- Available GLP studies: In a valid AMES test POEMA was found not to be mutagenic with or without metabolic activation. The outcome of a valid mouse lymphoma assay indicates that POEMA can have mutagenic properties in mammalian cells.
- Available non-GLP studies: There are no non-GLP studies available for the endpoint genetic toxicity.
- Historical human data: There are no historical human data that can be considered for this endpoint. The publicly available databases were consulted for information, but no data were found to further conclude on the genotoxicity of POEMA.
- (Q)SAR: The outcome of a QSAR assessment (eg an OECD toolbox assessment) is not considered sufficient information to fill the endpoint in vivo genetic toxicity.
- In vitro methods: The outcome of a valid mouse lymphoma assay triggered the necessity to perform an in vivo genotoxicity study, further in vitro testing was waived.
- Weight of evidence: The positive result in a mouse lymphoma assay indicates that POEMA potentially induces structural chromosome aberrations. To further address this mode-of-action, the In vivo alkaline single-cell gel electrophoresis assay for DNA strand breaks (COMET assay) is proposed. As the Comet assay addresses all potential mode-of-actions (structural chromosome aberrations and/or gene mutations), the outcome of this in vivo study will overrule any in vitro result, therefore further in vitro testing is omitted.
- Grouping and read-across: Read across to structurally related substances (with shared sub-structures) has been considered. No potential analogues were identified that could be used for read across.
- Substance-tailored exposure driven testing: Not applicable for genetic toxicity endpoint
- 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 specific rules for adaptation from column 1 as given in column 2 are not applicable for in vivo genotoxicity testing.
FURTHER INFORMATION ON TESTING PROPOSAL IN ADDITION TO INFORMATION PROVIDED IN THE MATERIALS AND METHODS SECTION:
- Details on study design: It is proposed to address the potential genotoxic properties of POEMA in an in vivo Comet assay. This assay addresses all potential mode-of-actions (the 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), performance of this in vivo study is considered to be sufficient to conclude on this endpoint. The oral route is considered to be the most appropriate route. As no sex-specific toxicity is expected, the test is performed in a single species. As no tissue-specific toxicity is expected, blood and liver samples will be tested.

Data source

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 489 (In vivo Mammalian Alkaline Comet Assay)
Version / remarks:
Most recent version
Deviations:
no
GLP compliance:
yes
Type of assay:
mammalian comet assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
liquid: viscous

Test animals

Species:
rat
Sex:
male

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
Propylene glycol

Examinations

Tissues and cell types examined:
Liver and blood

Results and discussion

Applicant's summary and conclusion