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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
Study period:
April 2011 to June 2011
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2011
Report date:
2011

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
GLP compliance:
yes (incl. QA statement)
Type of assay:
bacterial reverse mutation assay

Test material

Constituent 1
Reference substance name:
Potassium aluminium silicate amorphous glass fibres
EC Number:
931-219-8
Molecular formula:
SinO(3n-1)2(n-1) polymeric anions ionically bonded to Al3+ and K2+ cations
IUPAC Name:
Potassium aluminium silicate amorphous glass fibres
Test material form:
solid - liquid: suspension
Remarks:
migrated information: dispersion
Details on test material:
Name of test material (as cited in study report): Superwool 1400
- Substance type: Inorganic
- Physical state: Solid
- Analytical purity: >99%
- Impurities (identity and concentrations): trace impurities
- Purity test date: 14/12/09
- Lot/batch No.: BG-11-P19-2563
- Expiration date of the lot/batch: 31/12/2020
- Stability under test conditions: stable
- Storage condition of test material: room temperature, sealed container

Method

Target gene:
histidine
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 applicable
Species / strain / cell type:
S. typhimurium TA 102
Additional strain / cell type characteristics:
not applicable
Metabolic activation:
without
Metabolic activation system:
material is complete inorganic with no available groups for metabolism
Test concentrations with justification for top dose:
see table 1 in other information on methods section, rangefinder and mutation experiments were carried out.
Vehicle / solvent:
- Vehicle used: 1% methylcellulose (1% MC).
- Justification for choice of vehicle: The test article is insoluble in all commonly used vehicles that are compatible with the assay system. The test article will therefore be tested as a suspension in 1% MC. Ultrasonication will be used to aid homogeneity of the stock suspension and the formulations will be stirred continuously (using a magnetic stirrer) prior to addition to the test system.
Controlsopen allclose all
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
mitomycin C
Positive controls:
yes
Positive control substance:
sodium azide
Positive controls:
yes
Positive control substance:
2-nitrofluorene
Positive controls:
yes
Positive control substance:
9-aminoacridine
Details on test system and experimental conditions:
METHOD OF APPLICATION: in suspension

DURATION
- Preincubation period: 10 hours
- Exposure duration: 2 - 3 days
Evaluation criteria:
For valid data, the test article was considered to be mutagenic if:
1. Dunnett's test gave a significant response (p ≤ 0.01) which was concentration
related
2. the positive trend/effects described above were reproducible.
The test article was considered as positive in this assay if all of the above criteria were met.
The test article was considered as negative in this assay if none of the above criteria were met.
Statistics:
Dunnett's test was used to compare the counts at each concentration with the control.

Results and discussion

Test resultsopen allclose all
Species / strain:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Metabolic activation:
without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not determined
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Species / strain:
S. typhimurium TA 102
Metabolic activation:
without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not determined
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Additional information on results:
TEST-SPECIFIC CONFOUNDING FACTORS
- Water solubility: material is an insoluble inorganic solid

RANGE-FINDING/SCREENING STUDIES:
Initial toxicity Range-Finder Experiment was carried out in strain TA100 only, using final concentrations of AES Covance at 1.6, 8, 40, 200, 1000 and 5000 μg/plate, plus negative (vehicle) and positive controls. Following these treatments, no evidence of toxicity was observed, as would normally be indicated by a thinning of the background bacterial lawn and/or a marked reduction in revertant numbers.

COMPARISON WITH HISTORICAL CONTROL DATA:
Control counts were compared with the accepted normal ranges for our laboratory for numbers of spontaneous revertants on vehicle control plates
and numbers of induced revertants on positive control plates. Data were considered acceptable if the mean vehicle control counts fell within the historical 99% confidence intervals for group means and/or each vehicle control plate count fell within the historical 99% reference ranges, and the positive control plate counts were comparable with the historical 99% reference ranges. The ranges that are quoted are based on a large volume of historical
control data accumulated from experiments where the correct strain and assay functioning are considered to have been confirmed. Data for our laboratory are consistent with ranges of spontaneous revertants per plate considered acceptable elsewhere [7].

ADDITIONAL INFORMATION ON CYTOTOXICITY:
Initial toxicity Range-Finder Experiment was carried out in strain TA100 only, using final concentrations of AES Covance at 1.6, 8, 40, 200, 1000 and 5000 μg/plate, plus negative (vehicle) and positive controls. Following these treatments, no evidence of toxicity was observed, as would normally be indicated by a thinning of the background bacterial lawn and/or a marked reduction in revertant numbers.
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 without metabolic activation

It was concluded that Superwool 1400 sample did not induce mutation in five histidine-requiring strains (TA98, TA100, TA1535, TA1537 and TA102) of Salmonella typhimurium when tested under the conditions of this study. These conditions included treatments at concentrations up to 5000 μg/plate, in the absence of any exogenous metabolic activation system (as no microsomal metabolisable component is present in the test substsance).