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: Hydroxyfuranone
CONSIDERATIONS THAT THE GENERAL ADAPTATION POSSIBILITIES OF ANNEX XI OF THE
REACH REGULATION ARE NOT ADEQUATE TO GENERATE THE NECESSARY INFORMATION:
- Available GLP studies: Hydroxyfuranone was found to be mutagenic in tester strains TA100 in the Salmonella typhimurium reverse mutation assay and WP2uvrA in the Escherichia coli reverse mutation assay in a valid AMES test (CRL project 20153258). Hydroxyfuranone was found to be mutagenic both in absence and presence of metabolic activation.
- 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 Hydroxyfuranone (Literature search for Hydroxyfuranone (CAS 78920-10-2) CRL report no. 20125565, dd 9 January 2018).
- (Q)SAR: The outcome of a QSAR assessment (eg an OECD toolbox assessment) is not considered to yield reliable information to fill the endpoint in vivo genetic toxicity.
- In vitro methods: The outcome of a valid AMES test triggered the necessity to perform an in vivo genotoxicity study. A positive result in an AMES study indicates primary DNA damage. Additional in vitro tests can yield information on other potential genotoxic mode-of-actions. Primary DNA damage can be addressed in an in vivo COMET assay. Next to this potential mode-of action, the COMET assay also detects chromosome aberrations. Since all potential mode-of-actions will be addressed in the in vivo COMET assay, it was considered superfluous to perform further in vitro testing.
- Weight of evidence: 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, and 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 (Charles River Report on the evaluation of the applicability of an analogue approach for REACH registration of Hydroxyfuranone (CAS 78920-10-2), dd 15 March 2018).
- 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 Hydroxyfuranone (CAS 78920-10-2) 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

Test animals

Species:
rat
Sex:
male

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
To be determined at study initiation.

Results and discussion

Applicant's summary and conclusion