Registration Dossier

Toxicological information

Genetic toxicity: in vitro

Currently viewing:

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:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report date:
2012

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Type of assay:
bacterial reverse mutation assay

Test material

Constituent 1
Chemical structure
Reference substance name:
4,4'-Isopropylidenediphenol, ethoxylated
EC Number:
500-082-2
EC Name:
4,4'-Isopropylidenediphenol, ethoxylated
Cas Number:
32492-61-8
Molecular formula:
The substance is a UVCB and contains a series of homologues that have the general molecular formula C15H16O2.(C2H4O)n, where 2 ≤ n ≤ 10
IUPAC Name:
4,4'-Isopropylidenediphenol, ethoxylated
Test material form:
liquid: viscous

Method

Target gene:
Salmonella typhimurium: Histidine gene
Escherichia coli: Tryptophan gene
Species / strainopen allclose all
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Additional strain / cell type characteristics:
not specified
Species / strain / cell type:
E. coli WP2 uvr A
Additional strain / cell type characteristics:
not specified
Metabolic activation:
with and without
Metabolic activation system:
Liver S9 mix from induced rats
Test concentrations with justification for top dose:
Standard Plate Test (SPT): 0, 33, 100, 333, 1000, 2500 and 5000 µg/plate
Preincubation Test (PIT): 0, 10, 33, 100, 333, 1000 and 2500 µg/plate
Vehicle / solvent:
Dimethylsulphoxide (DMSO)
Controlsopen allclose all
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
not specified
Positive controls:
yes
Positive control substance:
other: 2-aminoanthracene (2-AA)
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
not specified
Positive controls:
yes
Positive control substance:
N-ethyl-N-nitro-N-nitrosoguanidine
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
not specified
Positive controls:
yes
Positive control substance:
other: 4-nitro-o-phenylenediamine (NOPD)
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
not specified
Positive controls:
yes
Positive control substance:
9-aminoacridine
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
not specified
Positive controls:
yes
Positive control substance:
4-nitroquinoline-N-oxide
Details on test system and experimental conditions:
Standard plate test (SPT) and preincubation test (PIT) both with and without metabolic activation (liver s( mix from induced rats). The rate of induced back mutations of several bacteria mutants from histidine auxotrophy (his(-)) to histidine prototrophy (his(+)) was determined in the Salmonella typhimurium strains. The rate of induced back mutations from tryptophan auxotrophy (trp(-)) to tryphtophan independence (trp(+)) was determined in the Escherichia coli strain.
Evaluation criteria:
Mutagenicity: Individual plate counts, the mean number of revertant colonies per plate and the standard deviations were given for all dose groups as well as for the positive and negative vehicle.
Titre: The titre is generally determined only in the experimental parts with S9 mix both for the negative controls (vehicle only) and for the two highest doses in all experiments.
Toxicity: Toxicity detected by a decrease in the number of revertants, clearing or diminution of the background lawn (= reduced his(-) or trp(-) background growth), or reduction in the titre, was recorded for all test groups both with and without S9 mix in all experiments.
Solubility: Precipitation of the test material was recorded.

Results and discussion

Test resultsopen allclose all
Species / strain:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Remarks:
Preincubation Test
Cytotoxicity / choice of top concentrations:
not determined
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Species / strain:
E. coli WP2 uvr A
Metabolic activation:
with and without
Genotoxicity:
negative
Remarks:
Preincubation Test
Cytotoxicity / choice of top concentrations:
not determined
Vehicle controls validity:
valid
Untreated negative 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:
not determined
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Species / strain:
E. coli WP2 uvr A
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not determined
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
A bacteriotoxic effect (reduced his(-) background growth, decrease in the number of his(+) or trp(+) revertants, reduction in the titre) was observed in the standard plate test depending on the strain and test conditions from about 2500 µg/plate onward. In the preincubation assay bacteriotoxicity (reduced his(-) background growth, decrease in the number of his(+) or trp(+) revertants, reduction in the titre) was observed depending on the strain and test conditions from about 1000 µg/plate onward. In addition, no test substance precipitation was found with and without S9 mix.
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
negative with metabolic activation
negative without metabolic activation

Under the experimental conditions chosen here, it is concluded that the test substance is not a mutagenic substance in the bacterial reverse mutation test in the absence and the presence of metabolic activation.
Executive summary:

Mutagenicity in Salmonella typhimurium (strain: TA 1535, TA 100, TA 1537 and TA 98) and Escherichia coli (strain: E. coli WP2 uvrA) was determined in accordance with the OECD Guideline for Testing of Chemicals 471. Mutagenicity was measured using the bacterial reverse mutation assay in the absence and the presence of metabolic activation (S9 mix). The evaluation criteria was an increase in the number of his(+) or trp(+) revertants, first in a standard plate test (SPT) and then in a preincubation test (PIT). The dose range used was 33 µg - 5000 µg/plate (SPT) and 10 µg - 2500 µg/plate (PIT). A biologically relevant increase in the number of his(+) or trp (+) revertants was not observed in the STP or in the PIT, both with and without S9 mix. A bacteriotoxic effect was observed depending on the strain and test conditions from about 1000 µg/plate onward. Thus, under the experimental conditions of this study, the test substance is not mutagenic in the Salmonella typhimurium/Escherichia coli reverse mutation assay in the absence and the presence of metabolic activation.