Registration Dossier

Administrative data

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

The potential mutagenic activity has been assessed using the Bacterial Reverse Mutation Assay (Ames test) according to OECD 471 and in compliance with GLP. The test item had mutagenic activity in Salmonella typhimurium TA1535 bacterial strains without metabolic activation. No mutagenic activity was observed in Salmonella typhimurium TA98, TA100, TA1537 and Escherichia coli WP2 uvrA bacterial strains with and without metabolic activation and Salmonella typhimurium TA1535 with metabolic activation under the test conditions used in this study.

The in vitro micronucleus test is being undertaken as additional data to assess the Ames test result.  Due to the availability of laboratory space, the study is schedule for completion after the phase-in deadline.  Consequently, to allow for registration of the substance and member registration by co-registrants, this registration is being submitted with the data pending.  The registrant will conduct the spontaneous update to to submit details of the data as soon as these become available, anticipated in Q3 or Q4 2018

Link to relevant study records

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Endpoint:
in vitro gene mutation study in bacteria
Type of information:
experimental study
Adequacy of study:
key study
Study period:
10 October - 12 November 2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Version / remarks:
Plate Incorporation method
Deviations:
yes
Remarks:
During the Confirmatory Mutation Test the incubation time was 21 minutes instead of 20 minutes in one case
GLP compliance:
yes (incl. certificate)
Type of assay:
bacterial reverse mutation assay
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2
Metabolic activation:
with and without
Metabolic activation system:
activated rat liver S9
Test concentrations with justification for top dose:
5000, 1581, 500, 158.1, 50 and 15.81 μg/plate
Vehicle / solvent:
Distilled water
Negative solvent / vehicle controls:
yes
Positive controls:
yes
Positive control substance:
methylmethanesulfonate
other: 4-nitro-1,2-phenylene-diamine
Key result
Species / strain:
S. typhimurium TA 1535
Metabolic activation:
without
Genotoxicity:
positive
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Positive controls validity:
valid
Key result
Species / strain:
S. typhimurium TA 1535
Metabolic activation:
with
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Positive controls validity:
valid
Key result
Species / strain:
S. typhimurium TA 1537
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Positive controls validity:
valid
Key result
Species / strain:
S. typhimurium TA 98
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Positive controls validity:
valid
Key result
Species / strain:
S. typhimurium TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Positive controls validity:
valid
Key result
Species / strain:
E. coli WP2 uvr A
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Positive controls validity:
valid

Based on the results of the Preliminary Concentration Range Finding Test, the test item concentrations were in the Initial Mutation Test (plate incorporation) with and without metabolic activation in Salmonella typhimurium TA98, TA100, TA1535, TA1537 and Escherichia coli WP2 uvrA strains 5000, 1581, 500, 158.1, 50 and 15.81 μg/plate. In the Confirmatory Mutation Test (pre-incubation) the examined test item concentrations were with and without metabolic activation in Salmonella typhimurium TA98, TA100, TA1535, TA1537 and Escherichia coli WP2 uvrA strains 5000, 1581, 500, 158.1, 50, 15.81 and 5 μg/plate. In the Complementary Initial Mutation Test (plate incorporation) the examined concentrations were in Salmonella typhimurium TA1535 strain without metabolic activation 5000, 3750, 2500, 1250, 625 and 312.5 μg/plate. In the case of Salmonella typhimurium TA1535 strain without metabolic activation, in the Initial Mutation Test a slight positive was observed, in the Complementary Initial Mutation Test a clear, reproducible positive effect was obtained using the plate incorporation method.

Precipitate of the test item was not detected in the Preliminary Concentration Range Finding Test and in the main tests.

No inhibitory, cytotoxic effect of the test item was observed in the preliminary experiment and in the main tests.

The mean values of revertant colonies of the solvent control plates were within the historical control range, the reference mutagens showed the expected increase in the number of revertant colonies, the viability of the bacterial cells was checked by a plating experiment in each test. At least five analysable concentrations were presented in all strains of the main tests.

Conclusions:
The test item had mutagenic activity in Salmonella typhimurium TA1535 bacterial strains without metabolic activation. No mutagenic activity was observed in Salmonella typhimurium TA98, TA100, TA1537 and Escherichia coli WP2 uvrA bacterial strains with and without metabolic activation and Salmonella typhimurium TA1535 with metabolic activation under the test conditions used in this study.
Executive summary:

The potential mutagenic activity has been assessed using the Bacterial Reverse Mutation Assay (Ames test) according to OECD 471 and in compliance with GLP. The test item had mutagenic activity in Salmonella typhimurium TA1535 bacterial strains without metabolic activation. No mutagenic activity was observed in Salmonella typhimurium TA98, TA100, TA1537 and Escherichia coli WP2 uvrA bacterial strains with and without metabolic activation and Salmonella typhimurium TA1535 with metabolic activation under the test conditions used in this study.

Endpoint:
in vitro cytogenicity / micronucleus study
Remarks:
The study is currently ongoing. This submission allows co-registrants to register for the deadline and the lead dossier will be spontaneously updated as soon as the result is available
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Not yet reported
Reliability:
1 (reliable without restriction)
Qualifier:
according to
Guideline:
OECD Guideline 487 (In vitro Mammalian Cell Micronucleus Test)
GLP compliance:
yes
Type of assay:
in vitro mammalian cell micronucleus test
Target gene:
L5178Y cells
Vehicle / solvent:
No information
Key result
Species / strain:
mouse lymphoma L5178Y cells
Metabolic activation:
with and without
Genotoxicity:
other: result not yet available
Cytotoxicity / choice of top concentrations:
other: not yet available
Vehicle controls validity:
other: not yet available
Untreated negative controls validity:
other: not yet available
Positive controls validity:
other: not yet available
Conclusions:
The in vitro micronucleus test is being undertaken as additional data to assess the Ames test result. Due to the availability of laboratory soace, the study is schedule for completion after the phase-in deadline. Consequently, to allow for registration of the substance and member registration by co-registrants, this registration is being submitted with the data pending. The registrant will conduct the spontaneous update to to submit details of the data as soon as these become available, anticipated in Q3 or Q4 2018
Executive summary:

The in vitro micronucleus test is being undertaken as additional data to assess the Ames test result.  Due to the availability of laboratory space, the study is schedule for completion after the phase-in deadline.  Consequently, to allow for registration of the substance and member registration by co-registrants, this registration is being submitted with the data pending.  The registrant will conduct the spontaneous update to to submit details of the data as soon as these become available, anticipated in Q3 or Q4 2018

Endpoint conclusion
Endpoint conclusion:
no study available (further information necessary)

Genetic toxicity in vivo

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification