Registration Dossier

Administrative data

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
Type of information:
experimental study planned
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: 4,4'-isopropylidenedicyclohexanol
- Name of the substance for which the testing proposal will be used: HBPA
CONSIDERATIONS THAT THE GENERAL ADAPTATION POSSIBILITIES OF ANNEX XI OF THE REACH REGULATION ARE NOT ADEQUATE TO GENERATE THE NECESSARY INFORMATION

- Available GLP studies:
Genetic Toxicity GMbact (Huntingdon Life Sciences, 2012, Study MOG0010)
Genetic Toxicity CAbvitro (Huntingdon Life Sciences, 2012, Study MOG0011)
Genetic Toxicity GMvitro Huntingdon Life Sciences, 2012, Study (MOG0012)

- Available non-GLP studies: Not available

- Historical human data: Not available

- (Q)SAR: Not available

- In vitro methods
Genetic Toxicity GMbact (Huntingdon Life Sciences, 2012, Study MOG0010)
Genetic Toxicity CAbvitro (Huntingdon Life Sciences, 2012, Study MOG0011)
Genetic Toxicity GMvitro Huntingdon Life Sciences, 2012, Study (MOG0012)

- Weight of evidence: Not available

- Grouping and read-across: Not available

- Other reasons: Chromosome aberration study in vitro (Genetic Toxicity CAbvitro; Huntingdon Life Sciences, 2012, Study MOG0011) indicated the potential for HBPA to induce chromosome aberrations in mammalian cells. Although this result suggests a concern for genotoxic effects in humans, the available data do not permit a thorough assessment of the effect, nor are they sufficient to reach a conclusion on classification. In accordance with REACH Annex VIII Column 2 Section 8.4 it is considered that an in-vivo test assessing chromosome aberration in mammals is justified to more fully investigate the potential for harm to humans.

FURTHER INFORMATION ON TESTING PROPOSAL IN ADDITION TO INFORMATION PROVIDED IN THE MATERIALS AND METHODS SECTION:
- Details on study design / methodology proposed: Due significant increases in numerical aberrations in the form of polyploidy in the in vitro cytogenetic test, the registrant proposes an in vivo Micronucleus Test (e.g. OECD 474) to also include staining for aneugenesis additionally incorporating a comet phase to investigate any potential DNA damage in the liver.

Data source

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: flakes
Details on test material:
- Name of test material (as cited in study report): Rikabinol HB
- Substance type: Monomer
- Physical state: Flakes
- Analytical purity: 95.6%
- Purity test date: 12 December 2011
- Lot/batch No.: 7095
- Expiration date of the lot/batch: 31 December 2012
- Storage condition of test material: Room temperature, in the dark

Results and discussion

Applicant's summary and conclusion