Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
Type of information:
experimental study planned
Study period:
2020
Justification for type of information:
TESTING PROPOSAL ON VERTEBRATE ANIMALS

NON-CONFIDENTIAL NAME OF SUBSTANCE:
- Tetra methyl butyl hydroquinone

CONSIDERATIONS THAT THE GENERAL ADAPTATION POSSIBILITIES OF ANNEX XI OF THE REACH REGULATION ARE NOT ADEQUATE TO GENERATE THE NECESSARY INFORMATION:
- Available GLP studies : There are no available in vivo GLP studies that address the potential of the substance to cause cytogenetic damage.
- Available non-GLP studies : No in vivo non-GLP studies are available that address the potential of the substance to cause cytogenetic damage.
- Historical human data : There is no historical human data that is relevant to the endpoint “Genetic toxicity in vivo”.
- (Q)SAR : It is not possible to reliably estimate the in vivo potential for the test substance to cause cytogenetic damage using (Q)SAR calculation(s) or profilers.
- In vitro methods : Column 2 of the REACH Regulation (EC) No. 1907/2006, Annex VIII, 8.4, states that “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”. The test substance was found to be positive in an in vitro micronucleus test according to OECD guideline 487 in the extended (24-h) treatment of V79 cells. Therefore, using in vitro methods is not adequate to generate the necessary information.
- Weight of evidence : No data suitable for a Weight of Evidence approach to meeting the data requirements for the endpoint “Genetic toxicity in vivo” is available.
- Grouping and read-across : Grouping and read-across may not be used to meet the data requirements as there are no adequate analogue substances with suitable data.

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 “Specific rules for adaptation from Column 1" that are given in Column 2, 8.4 of the REACH Regulation (EC) No. 1907/2006, Annex VIII, 8.4, states that “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”. In an in vitro micronucleus test according to OECD guideline 487 performed with the test substance, the result was positive in the extended (24-h) treatment of V79 cells without metabolic activation and negative in the short-term (3-h) treatment of V79 cells with and without metabolic activation. There are no other specific adaptation possibilities of Annex VI to X (and Column 2 thereof) of the REACH Regulation that allow the waiving of an in vivo genotoxicity study under the above-mentioned circumstances.

Data source

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
Deviations:
no
Principles of method if other than guideline:
AF-317 was found to be positive in an in vitro micronucleus test according to OECD Guideline 487 (hameln rds, 2019) in the extended (24-h) treatment of V79 cells. The in vivo Mammalian Erythrocyte Micronucleus Test (according to OECD Guideline 474) is an adequate test to further investigate the potential of AF-317 to induce structural or numerical chromosome aberrations in vivo.
GLP compliance:
yes
Type of assay:
mammalian erythrocyte micronucleus test

Test material

Constituent 1
Chemical structure
Reference substance name:
2,5-bis(1,1,3,3-tetramethylbutyl)hydroquinone
EC Number:
212-990-3
EC Name:
2,5-bis(1,1,3,3-tetramethylbutyl)hydroquinone
Cas Number:
903-19-5
Molecular formula:
C22H38O2
IUPAC Name:
2,5-bis(1,1,3,3-tetramethylbutyl)hydroquinone

Test animals

Species:
other: mouse or rats

Administration / exposure

Route of administration:
oral: gavage

Results and discussion

Applicant's summary and conclusion

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