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Toxicological information

Genetic toxicity: in vitro

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Administrative data

Endpoint:
in vitro gene mutation study in bacteria
Remarks:
Type of genotoxicity: gene mutation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2008
Report Date:
2008

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Qualifier:
according to
Guideline:
EPA OPPTS 870.5100 - Bacterial Reverse Mutation Test (August 1998)
Qualifier:
according to
Guideline:
other: EEC: Directive 2000/32/EC, Council Directive 67/548/EEC, EEC Publication No. L136 (2000)
GLP compliance:
yes
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent

Method

Species / strainopen allclose all
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Species / strain / cell type:
E. coli WP2 uvr A
Metabolic activation:
with and without
Metabolic activation system:
rat liver S9, Aroclor induced
Test concentrations with justification for top dose:
33.3, 100, 333, 1000, 2000, and 5000 μg per plate
Controls
Negative solvent / vehicle controls:
yes
Positive controls:
yes
Positive control substance:
other: see below

Results and discussion

Test resultsopen allclose all
Species / strain:
E. coli WP2 uvr A
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
other: not detectable due to precipitate at high doses
Vehicle controls validity:
valid
Positive controls validity:
valid
Species / strain:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
other: not detectable due to precipitate at high doses
Vehicle controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Applicant's summary and conclusion

Conclusions:
Interpretation of results:
negative

The results of the Salmonella-Escherichia coli/Mammalian-Microsome Reverse Mutation Assay Preincubation Method with a Confirmatory Assay with 6,6'-[[3,3',5,5'-tetrakis(1,1-dimethylethyl)-[1,1'- biphenyl]-2,2'-diyl] bis(oxy)]bis-dibenzo[d,f][1,3,2]-dioxaphosphepin indicate that under the conditions of this study, the test article did not cause a positive increase in the mean number of revertants per plate with any of the tester strains either in the presence or absence of microsomal enzymes prepared from Aroclor™-induced rat liver (S9).
Executive summary:

The objective of this study was to evaluate the test article, 6,6'-[[3,3',5,5'-tetrakis(1,1-dimethylethyl)-[1,1'- biphenyl]-2,2'-diyl] bis(oxy)]bis-dibenzo[d,f][1,3,2]-dioxaphosphepin and/or its metabolites, for the ability to induce reverse mutations either in the presence or absence of mammalian microsomal enzymes at 1) the histidine locus in the genome of several strains of Salmonella typhimurium and at 2) the tryptophan locus of Escherichia coli strain WP2uvrA. This assay satisfied the following guidelines: U.S. EPA (1998), EEC (2000), and OECD (1997).

The concentrations tested in the mutagenicity assay were selected based on the results of a rangefinding study using tester strains TA100 and WP2uvrA and seven concentrations of test article ranging from 10.0 to 5000 μg per plate, two plates per concentration, both in the presence and absence of S9 mix. The tester strains used in the mutagenicity assay were Salmonella typhimurium tester strains TA98, TA100, TA1535, and TA1537 and Escherichia coli tester strain WP2uvrA. The assay was conducted with six concentrations of test article in the presence and absence of S9 mix, along with concurrent vehicle control and positive controls using three plates per concentration. In the mutagenicity assay, the concentrations tested with all tester strains were 33.3, 100, 333, 1000, 2000, and 5000 μg per plate in the presence and absence of S9 mix. The results of the initial mutagenicity assay were confirmed in an independent experiment.

The results of the Salmonella-Escherichia coli/Mammalian-Microsome Reverse Mutation Assay Preincubation Method with a Confirmatory Assay with test material indicate that under the conditions of this study, the test article did not cause a positive increase in the mean number of revertants per plate with any of the tester strains either in the presence or absence of microsomal enzymes prepared from Aroclor™-induced rat liver (S9).