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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:
16 May to 8 September 2003
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
Minor deviations (plate not incubated in closed system), not expected to affected study validity

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2004
Report Date:
2004

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
yes
Remarks:
The plates were incubated for approximately 72 hours at 37ºC. Due to an oversight the plates were not incubated in closed containers. The study authors felt that this deviation was not considered to have affected the integrity of the study.
GLP compliance:
yes
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Pt-divinyltetramethyldisiloxane
- Substance type: colourless
- Physical state: liquid
- Analytical purity: no data
- Lot/batch No.: DA3020190
- Expiration date of the lot/batch: no data
- Stability under test conditions: no data
- Storage condition of test material: at room temperature; solutions prepared immediately before testing

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:
Phenobarbital and betanaphthoflavone-induced Sprague-Dawley rat liver S9.
Test concentrations with justification for top dose:
See attachment
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: acetone
Controlsopen allclose all
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
yes
Positive controls:
yes
Positive control substance:
sodium azide
Positive controls:
yes
Positive control substance:
9-aminoacridine
Positive controls:
yes
Positive control substance:
2-nitrofluorene
Positive controls:
yes
Positive control substance:
methylmethanesulfonate
Positive controls:
yes
Positive control substance:
other: 2-aminoanthracene
Details on test system and experimental conditions:
METHOD OF APPLICATION: pre-incubation (Test 1) and in agar (plate incorporation) (Test 2)

DURATION
- Exposure duration: incubated for 72 hrs

NUMBER OF REPLICATIONS:
Duplicate (in Test 1) and triplicate (in Test 2)

DETERMINATION OF CYTOTOXICITY
Other: Thinning of background lawn

Evaluation criteria:
A two-fold or more increase in mean revertant numbers must be observed in two consecutive dose-levels or at the highest practicable dose level. In addition, there must be evidence of a dose-response relationship.
Statistics:
Regression analysis fits a regression line to the data by the least squares method, after root transformation of the plate counts.

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
Cytotoxicity / choice of top concentrations:
cytotoxicity
Vehicle 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:
cytotoxicity
Vehicle controls validity:
valid
Positive controls validity:
valid
Additional information on results:
TEST-SPECIFIC CONFOUNDING FACTORS
- Effects of pH: no data
- Effects of osmolality: no data
- Evaporation from medium: no data
- Water solubility: no data
- Precipitation: Precipitation of the test material was noted at 2500 and 5000 ug/plate in both tests, and in the first test also at 1600 ug/plate

RANGE-FINDING/SCREENING STUDIES: In the toxicity test, performed using the pre-incubation method, thinning of the background lawn was observed in all strains (with and without S9) at the higher dose-levels, except TA 98.

COMPARISON WITH HISTORICAL CONTROL DATA: yes (with and without S9)

Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Applicant's summary and conclusion

Conclusions:
No evidence of mutagenic activity was detected in S. typhimurium strains TA 98, TA 100, TA 1535, and TA 1537, or in Escherichia coli strain WP2 uvrA, tested with Pt-divinyltetramethyldisiloxane at up to 5000 ug/plate in the presence or absence of a rat liver (S9) metabolic activation system.
Executive summary:

Pt-divinyltetramethyldisiloxane was examined for mutagenic activity in four histidine-dependant auxotrophs of Salmonella typhimurium (TA98, TA100, TA1535, and TA1537) and in Escherichia coli strain WP2 uvrA, in the absence or presence of S9, using both the pre-incubation method (Test 1) and plate incorporation method (Test 2). The test was conducted according to OECD Test Guideline 471 and to GLP.

 

The test material did not induce two-fold increases in the number of revertant colonies in the pre-incubation or plate incorporation assay, at any dose-level, in any tester strain, in the absence or presence of S9. In both tests, precipitation was noted at 2500 ug/plate and above, and also at 1600 ug/plate in test 1. Toxicity, as indicated by thinning of the background lawn, was observed at higher dose levels in all tester strains (with and without S9), except TA98.

 

In conclusion, no evidence of mutagenic activity was detected in S. typhimurium strains TA98, TA100, TA1535, and TA1537, or in Escherichia coli strain WP2 uvrA, tested with Pt-divinyltetramethyldisiloxane at up to 5000 ug/plate in the presence or absence of S9.