Registration Dossier

Diss Factsheets

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

In accordance with REACH Regulation (1907/2006) Annex VIII column 2 point 8.4 "appropriate in vivo mutagenicity studies shall be considered in case of a positive result in any of the genotoxicity studies in Annex VII or VIII". Hydroxyacetone was negative in an in vitro gene mutation test in mammalian cells (OECD 476). However, hydroxyacetone was positive in a bacteria gene mutation (OECD 471, GLP) and in an in vitro mammalian cytogenicity assay (OECD 473, GLP). Based on these positive results an in vivo Comet assay conducted according to OECD 489 is considered appropriate to fulfil data requirements of Annex VIII of the REACH Regulation.

NON-CONFIDENTIAL NAME OF SUBSTANCE:
Hydroxyacetone

CONSIDERATIONS THAT THE GENERAL ADAPTATION POSSIBILITIES OF ANNEX XI OF THE REACH REGULATION ARE NOT ADEQUATE TO GENERATE THE NECESSARY INFORMATION:

- Available GLP studies:
In-vitro Gene Mutation Study in Bacteria (OECD 471), In-vitro Gene Mutation Study in Mammalian Cells (OECD 476), in-vitro Chromosome Aberration (OECD 473)

- Available non-GLP studies: None available

- Historical human data: no data

- (Q)SAR:
Profiling with OECD QSAR Toolbox v4.3 revealed a positive alert for micronucleus mutagenicity (profiler: in vivo mutagenicity (Micronucleus) alerts by ISS). The structural alert is H-acceptor-path3-H-acceptor. “This alert explores the possibility that a chemical interacts with DNA and/or proteins via non-covalent binding, such as DNA intercalation or groove-binding (Snyder et al. 2006). Among the descriptors potentially accounting for non-covalent interactions, the present molecular framework representing two bonded atoms connecting two H bond acceptors (calculated with software Leadscope Enteprise 2.4.15-6) resulted in an increased sensitivity/specificity for what concerns the Micronucleus training set” (Explanation tool of OECD QSAR Toolbox v4.3.1).

- In vitro methods: In-vitro Gene Mutation Study in Bacteria (OECD 471), In-vitro Gene Mutation Study in Mammalian Cells (OECD 476), in-vitro Chromosome Aberration (OECD 473)
- Weight of evidence:
- Grouping and read-across: Data for the structural analogues acetone (CAS 67-64-1) and dihydroxyacetone (CAS 96-26-4) are available.
Acetone – negative in erythrocyte micronucleus assay (ECHA disseminated dossier)
Dihydroxyacetone – negative in erythrocyte micronucleus assay (ECHA disseminated dossier)

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 following adaptations are possible according to REACH Regulation (1907/2006) Annex VIII column 2
8.4.2. The study does not usually need to be conducted
– if adequate data from an in vivo cytogenicity test are available or
– the substance is known to be carcinogenic category 1 or 2 or mutagenic category 1, 2 or 3.
8.4.3. The study does not usually need to be conducted if adequate data from a reliable in vivo mammalian gene mutation test are available.
The above mentioned adaptations are not applicable. Based on the available genotoxicity studies, there is some limited indication for genotoxicity in bacterial cells for hydroxyacetone. There is also an indication for cytogenicity in mammalian cells. Hence a further in vivo Comet assay conducted according to OECD 489 is considered appropriate to fulfil data requirements of Annex VIII of the REACH Regulation.

Data source

Materials and methods

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

Test material

Constituent 1
Chemical structure
Reference substance name:
Hydroxyacetone
EC Number:
204-124-8
EC Name:
Hydroxyacetone
Cas Number:
116-09-6
Molecular formula:
C3H6O2
IUPAC Name:
1-hydroxypropan-2-one

Results and discussion

Applicant's summary and conclusion