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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:
1989
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:
1989
Report date:
1989

Materials and methods

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

Test material

Constituent 1
Chemical structure
Reference substance name:
[(butoxymethylethoxy)methylethoxy]propan-1-ol
EC Number:
259-910-3
EC Name:
[(butoxymethylethoxy)methylethoxy]propan-1-ol
Cas Number:
55934-93-5
Molecular formula:
C13H28O4
IUPAC Name:
[(butoxymethylethoxy)methylethoxy]propan-1-ol
Details on test material:
- Name of test material (as cited in study report): Ttripropylene glycol-n-butyl ether
- Molecular formula (if other than submission substance): C13H28O4
- Molecular weight (if other than submission substance): 248

- Physical state: liquid
- Analytical purity:96.12%
- Impurities (identity and concentrations):

- Lot/batch No.: EB880621R004

Method

Species / strain
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Metabolic activation:
with and without
Metabolic activation system:
rat liver homogenate
Test concentrations with justification for top dose:
50, 158, 500, 1580, & 5000.0 µg/plate
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: DMSO
Controls
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: 2 aminoanthramine for all the strains in the absence of S9, sodium azide-S9TA 100 & TA 1535, 2NF -S9 in TA 100, 2AA -S9 in TA 1537
Details on test system and experimental conditions:
Type: Ames test

METHOD OF APPLICATION: preincubation

DURATION
- Preincubation period: 30 min
- Incubation period: 48 hours

NUMBER OF REPLICATIONS:
3 replicates per dose

DETERMINATION OF CYTOTOXICITY
- Method: bacterial background lawn evaluation

Evaluation criteria:
Concentrations of the test chemical which are overtly toxic are easily visualized as showing no bacterial growth on the plate (i.e. absence of background lawn). Lower levels of toxicity may be seen as a thin or sparse bacterial lawn, a reduction in the number of revertants, or the appearance of microcolonies (overgrown background lawn). Positive and negative controls were run concurrently with the test chemical, and appropriate responses for these controls are prerequesites for evaluating the response of the bacteria to the test chemical.

A test chemical is considered a bacterial mutagen if both the mean number of revertant colonies observed is at least three times higher than the mean of the negative (solvent) control and at the same time it produces a dose response relationship over several concentrations. If a chemical produces reproducible reversion rates in excess of 3x over background, but no definitive dose response relationship, it is considered to be a presumptive bacterial mutagen. If a chemical produces reproducible reversion rates greater than 2x but less than 3x over the negative controls, the results are considered to be equivocal or inconclusive. Test substances failing to meet the above criteria are considered non-mutagenic in this system.

Results and discussion

Test results
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
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:


RANGE-FINDING/SCREENING STUDIES: was conducted
COMPARISON WITH HISTORICAL CONTROL DATA: was done
ADDITIONAL INFORMATION ON CYTOTOXICITY:no cytotoxicity was observed
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Any other information on results incl. tables

see the attached word doc for tables.

Applicant's summary and conclusion

Conclusions:
Interpretation of results
negative

DOWANOL TPnB did not induce a mutagenic response in any of the tester strains as judged by the frequency of histidine-independent (his+) revertants. Hence, DOWANOL TPnB was  classified as negative in the Ames test under the experimental conditions used.
Executive summary:

TriPropylene glycol- n-butyl ether was evaluated in the Salmonella/mammalian-microsome bacterial mutagenicity assay (Ames test) using a pre-incubation modification of the standard assay. The test was conducted both in the presence and in the absence of externally supplied metabolic activation system. The test was conducted using Salmonella typhimurium bacetrial tester strains TA98, TA100, TA1535 and TA1537. The test agent was initially assayed in TA100 at concentrations of 0 (solvent control), 5.0, 15.8, 50.0, 158.0, 500.0, 1580.0 and 5000.0 micrograms/plate. The test material was assayed at least two times in each tester strain up to a maximum concentration of 5000 ug/plate.

In addition to the mutation in the histidine operon, these tester strains contain other mutations that increase their ability to detect mutagens.

Based upon the results in TA100, the top five concentrations were repeated in TA98, TA100, TA1535 and TA1537. The assay was repeated independently at the same five concentrations using all four tester strains. The test material did not induce a mutagenic response in any of the tester strains in either of the assays as judged by the frequencies of histidine-independent (his+) revertants. Hence, the test material was classified as negative in the under the experimental conditions used.