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

Hazard endpoint for which vertebrate testing was proposed:
In vivo mammalian alkaline comet assay (test method: OECD TG 489)

NON-CONFIDENTIAL NAME OF SUBSTANCE:
2-tert-butyl-1,4-dimethoxybenzene

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:Structural activity alert for in vivo mutagenicity (DNA binding alerts Michael addition: P450 Mediated Activation to Quinones and Quinone-type Chemicals)
- In vitro methods: no in vitro methods are available to cover all the endpoints evaluated by an OECD 489 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 ames (OECD 471) and the micronucleus (OECD 487) study were both concluded as negative however results from the mammalian cell (OECD 490) study produced a positive result with metabolic activiation (+S9) but negative in the absence of S9.

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 rat following oral gavage dosing. The comet assay can be applied to almost every tissue of an animal from which single cell or nuclei suspensions can be made, including specific site of contact tissues.

Data source

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 489 (In vivo Mammalian Alkaline Comet Assay)
GLP compliance:
yes
Type of assay:
mammalian comet assay

Test material

Constituent 1
Chemical structure
Reference substance name:
2-tert-butyl-1,4-dimethoxybenzene
EC Number:
244-216-5
EC Name:
2-tert-butyl-1,4-dimethoxybenzene
Cas Number:
21112-37-8
Molecular formula:
C12H18O2
IUPAC Name:
2-tert-butyl-1,4-dimethoxybenzene
Test material form:
liquid

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female

Administration / exposure

Route of administration:
oral: gavage

Results and discussion

Applicant's summary and conclusion