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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:
Dec 1995 to Aug 1996
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP-study according to OECD guideline 471.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1996
Report date:
1996

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Qualifier:
according to guideline
Guideline:
EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.5265 (The Salmonella typhimurium Bacterial Reverse Mutation Test)
Qualifier:
according to guideline
Guideline:
OECD Guideline 472 (Genetic Toxicology: Escherichia coli, Reverse Mutation Assay)
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.5100 - Bacterial Reverse Mutation Test (August 1998)
GLP compliance:
yes (incl. QA statement)
Type of assay:
bacterial reverse mutation assay

Test material

Constituent 1
Chemical structure
Reference substance name:
1-propoxypropan-2-ol
EC Number:
216-372-4
EC Name:
1-propoxypropan-2-ol
Cas Number:
1569-01-3
Molecular formula:
C6H14O2
IUPAC Name:
1-propoxypropan-2-ol
Details on test material:
- Name of test material (as cited in study report): Propylene glycol n-propyl ether (DOWANOL PnP)
- Physical state: clear colorless liquid
- Lot/batch No.: 950720

Method

Target gene:
Induction of reverse mutations at the histidine locus of S. typhimurium and the tryptophan locus in E. coli.
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
Additional strain / cell type characteristics:
not applicable
Species / strain / cell type:
E. coli WP2 uvr A
Details on mammalian cell type (if applicable):
not applicable
Additional strain / cell type characteristics:
not applicable
Metabolic activation:
with and without
Metabolic activation system:
S9 Mix
Test concentrations with justification for top dose:
0, 100, 333, 1000, 3330 and 5000 µg/plate
Vehicle / solvent:
Water
Controls
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: 2-aminoanthracene (TA98, TA100, TA1535, TA1537, WP2uvrA/+S9); 2-nitrofluorene (TA98/-S9); sodium azide (TA100, TA1535/-S9); ICR-191 (TA1537/-S9); 4-nitroquinoline-N-oxide (WP2uvrA/-S9)
Details on test system and experimental conditions:
METHOD OF APPLICATION: preincubation

DURATION
- Preincubation period: 20 min
- Incubation period: 48 hours

NUMBER OF REPLICATIONS: 3 replicates per dose / 2 independent experiments

DETERMINATION OF CYTOTOXICITY
- Method: bacterial background lawn evaluation (decrease in number of revertant colonies
- no cytotoxicity observed

Evaluation criteria:
For a test article to be considered positive, it had to produce at least a 3-fold increase in the mean revertants per plate of at least one tester strain over the mean revertants per plate of the appropriate vehicle control. This 3-fold or greater increase in the mean number of revertants per plate had to be observed at more than one dose and had to be accompanied by a dose response to increasing concentrations of the test article. In addition, the observed dose-responsive increase had to be shown to be reproducible. An observed response which did not meet all three of the above criteria (magnitude, dose-responsiveness, reproducibility) was not evaluated as positive.
Statistics:
None

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:
no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
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:
no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
Vehicle controls validity:
valid
Untreated negative 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 (migrated information):
negative

The results of the Salmonella - Escherichia coli/Mammalian-Microsome Reverse Mutation Assay, Preincubation Method, with a Confirmatory Assay, indicate that, under the conditions of this study, in both an initial and confirmatory assay, test article, Propylene glycol n-propyl ether, did not cause a positive increase in the number of revertants per plate of any of the tester strains either in the presence or absence of microsomal enzymes prepared from Aroclor-induced liver (S9).
Executive summary:

Propylene glycol n-propyl ether (DOWANOL PnP), was evaluated in the Salmonella-Escherichia coli/mammalian-microsome bacterial mutagenicity assay using a pre-incubation modification of the standard assay. The test was conducted in the presence and absence of an externally supplied metabolic activation system (S-9) using Salmonella typhimurium tester strains TA98, TA100, TA1535, and TA1537 and Escherichia coli tester strain WP2ucrA. The concentrations of the test material assay ranged from 100 to 5000 µg/plate. The test material did not induce a positive increase in the number of revertant colonies in any of the tester strains either in the presence or absence of the external metabolic activation system. The results were confirmed in an independent assay. Hence, propylene glycol n-propyl ether (DOWANOL PnP) was classified as negative in this bacterial mutagenicity test under experimental conditions used.

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