Registration Dossier

Administrative data

Endpoint:
in vivo mammalian somatic cell study: gene mutation
Type of information:
experimental study planned
Study period:
awaiting agreement to ECHA
Justification for type of information:
CONSIDERATIONS OF ALTERNATIVE METHODS ON TESTING PROPOSALS IN YOUR REGISTRATION

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

Considerations that the general adaptation possibilities of Annex XI of the REACH Regulation were not adequate to generate the necessary information

• available GLP studies
None.

• available non-GLP studies
None.

• historical human data
None.

• (Q)SAR
No reliable QSAR model is available to replace the in vivo Comet assay in rodents.

• in vitro methods
Ames test (OECD 471) and in vitro micronucleus test (OECD 487) have already performed on the registered substance. As the results are positive in micronucleus test, an in vivo study is required to evaluate the relevance of the in vitro positive results.

• weight of evidence
No sufficient data is available which allow a weight of evidence approach.

• grouping and read-across
None

• substance-tailored exposure driven testing [if applicable]
Not applicable

• [approaches in addition to above [if applicable]
Not applicable

• other reasons [if applicable]
None


Considerations that the specific adaptation possibilities of Annexes VI to X (and column 2 thereof) were not applicable:

Test proposal is fully compliant with ECHA guidance R 7.a (2017, page 575).
No specific adaptation possibilities of Annexes VI to X (and column 2 thereof) are applicable.

According to the OECD guidance R7A, when the in vitro micronucleus study was positive, an in vivo study could be proposed instead of launching the in vitro gene mutation test on mammalian cells. Indeed, with one positive in vitro test, an in vivo study is required in the REACH regulation. The in vivo alkaline comet assay (OECD 489) 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. 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.

Proposed design of the OECD 489 study : The proposed species is rat, common species for this type of test. Gavage is proposed as route of exposure. Three target organs are proposed : stomach and duodenum, considered as the first organs exposed to the substance (with gavage exposure), and liver, principal organ of metabolism.

Data source

Materials and methods

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

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat

Administration / exposure

Route of administration:
oral: gavage

Results and discussion

Applicant's summary and conclusion