Registration Dossier

Administrative data

Endpoint:
in vivo mammalian cell study: DNA damage and/or repair
Type of information:
experimental study planned
Justification for type of information:
TESTING PROPOSAL ON VERTEBRATE ANIMALS
Genetic toxicity in vivo

NON-CONFIDENTIAL NAME OF SUBSTANCE:
Fatty acids, C18-unsatd., dimers, polymers with epichlorohydrin

CONSIDERATIONS THAT THE GENERAL ADAPTATION POSSIBILITIES OF ANNEX XI OF THE REACH REGULATION ARE NOT ADEQUATE TO GENERATE THE NECESSARY INFORMATION:
- Available GLP studies: No studies available
- Available non-GLP studies: No studies available
- Historical human data: No data available
- (Q)SAR: It is acknowledged that the results of QSAR modelling are of very limited applicability to UVCB substances, therefore QSAR prediction is not applicable for this substance.
- In vitro methods: no in vitro methods are available to cover all the endpoints evaluated by an OECD 89 study
- Weight of evidence: not enough data to build a weight of evidence.
- Grouping and read-across: Read across substances are not available.
- Substance-tailored exposure driven testing: Inhalation is not an expected route of exposure therefore testing via the inhalation route is 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 in-vitro data available for test substance such as the Chromosome Aberration study and the Mousy Lymphoma study were both concluded as negative however results from the Ames study produced a positive result in only one strain. We believe this result is a real genotoxic event in the bacteria and therefore overall the Ames study was concluded as a positive result.
In-vivo data are not available for this substance.
Based on the information above it is not possible to conclude classification for genetic toxicity and as outlined in the Integrated Testing Strategy (ITS) for mutagenicity (ECHA, 2017) “if there is a positive result in any of the in vitro studies from Annex VII or VIII and there are no appropriate results available from an in vivo study already, an appropriate in vivo somatic cell genotoxicity study should be proposed.”

FURTHER INFORMATION ON TESTING PROPOSAL IN ADDITION TO INFORMATION PROVIDED IN THE MATERIALS AND METHODS SECTION:
- In order to assess the potential to induce genotoxicity in vivo, an alkaline comet assay (OECD Test Guideline 489 is proposed. The purpose of the comet assay is to identify substances that cause DNA damage, by detecting single and double stranded breaks. “These strand breaks may be repaired, resulting in no persistent effect, may be lethal to the cell, or may be fixed into a mutation resulting in a permanent viable change. They may also lead to chromosomal damage which is also associated with many human diseases including cancer” (OECD, 2016). It is proposed to conduct this study in mice following oral gavage dosing.

Data source

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 489 (In vivo Mammalian Alkaline Comet Assay)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Details on test material:
Identification: Fatty acids, C18-unsatd., dimers, polymers with epichlorohydrin
Batch: 52611021
CAS Number: 68475-94-5
EC Number: 500-215-4
Purity: 95-100%
Physical state / Appearance: Clear yellow liquid
Expiry Date: 01 December 2018
Storage Conditions: Room temperature in the dark

Results and discussion

Applicant's summary and conclusion