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Toxicological information

Genetic toxicity: in vitro

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Administrative data

Endpoint:
in vitro gene mutation study in bacteria
Type of information:
experimental study
Adequacy of study:
key study
Study period:
No data
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1982
Report Date:
1982

Materials and methods

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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Details on test material:
Name of test material: Trimethylolpropanepoly(oxypropylene)triamine
EC no.: 500-105-6
CAS no.: 39423-51-3
Physical state: clear colourless liquid
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: J-98

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: no data
- Stability under test conditions: no apparent change in the physical state of the test or control articles during the assay

OTHER SPECIFICS:
- Name of test material (as cited in study report): 4236-44-30

Method

Species / strainopen allclose all
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Details on mammalian cell type (if applicable):
not applicable
Species / strain / cell type:
S. typhimurium TA 1538
Details on mammalian cell type (if applicable):
not applicable
Metabolic activation:
with and without
Metabolic activation system:
S-9 fraction of rat liver homogenate obtained from Arcolor 1254-treated Sprague Dawley rats
Test concentrations with justification for top dose:
12, 40, 120, 400 and 1200 µg/plate
Vehicle / solvent:
-solvent(s) used: distilled water
Controlsopen allclose all
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
Remarks:
with and without metabolic activation
True negative controls:
no
Positive controls:
yes
Remarks:
without metabolic activation
Positive control substance:
sodium azide
Remarks:
TA1535 and TA100=10 µg/ml
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
Remarks:
with and without metabolic activation
True negative controls:
no
Positive controls:
yes
Remarks:
without metabolic activation
Positive control substance:
2-nitrofluorene
Remarks:
TA1538 and TA98=50 µg/ml
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
Remarks:
with and without metabolic activation
True negative controls:
no
Positive controls:
yes
Remarks:
without metabolic activation
Positive control substance:
9-aminoacridine
Remarks:
TA1537=1500 µg/ml
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
Remarks:
with and without metabolic activation
True negative controls:
no
Positive controls:
yes
Remarks:
with metabolic activation
Positive control substance:
other: 2-anthramine
Remarks:
in all strains=50 µg/ml
Details on test system and experimental conditions:
METHOD OF APPLICATION: in agar (plate incorporation);


DURATION
- Preincubation period: 48h
- Exposure duration: 48-72h



SELECTION AGENT (mutation assays): histidine and biotin



NUMBER OF REPLICATIONS:
positive and negative controls: in triplicate
treated groups: in duplicate
tester strains: treated with five levels of the test compound




DETERMINATION OF CYTOTOXICITY
- Method: growth inhibition is tetsted at the following concentrations: 10,000, 3333, 1000, 333 and 100 µg/plate with strains TA1538 and TA100 ( in duplicate).

Evaluation criteria:
revertant colonies are counted (Artek Counter Model 880)
- positive result is defined as a reproducible, dose-related increase in the number of histidine-independent colonies
- negative result is defined as the absence of a reproducible increase in the number of histidine-independent colonies



Results and discussion

Test resultsopen allclose all
Key result
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:
not examined
Positive controls validity:
valid
Key result
Species / strain:
S. typhimurium TA 1538
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
not examined
Positive controls validity:
valid
Key result
Species / strain:
S. typhimurium TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
not examined
Positive controls validity:
valid
Additional information on results:
RANGE-FINDING/SCREENING STUDIES: dose levels for the Preliminary Toxicity Screen were 10,000, 3333, 1000, 333 and 100 µg/plate.
Tester Strains TA1538 and TA100 showed complete inhibition at 10,000 ug/plate, excessive inhibition at 3333 µg/plate and moderate inhibition a t 1000 µg/plate.


COMPARISON WITH HISTORICAL CONTROL DATA: all positive and negative controls were within acceptable range of mean historical data


Remarks on result:
other: all strains/cell types tested

Applicant's summary and conclusion

Conclusions:
The results for the test article 4236-44-30, Order# 5-98, were negative in strains TA1535, TA1537, TA1538, TA98 and TA100 of Salmonella typhimurium both with and without metabolic activation preparation at 1200, 400, 120, 40 and 12 µg/plate.