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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:
06/1987-11/1987
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:
1987
Report Date:
1987

Materials and methods

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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Identity: Dowanol-PnB (1-butoxy-2-hydroxypropane or propylene glycol normal-butyl ether). CAS # 29387-86-8 (also 5131-66-8). Batch No.: XZ 95410.00. Purity: >98% Supplied as: Not reported. Appearance: Transparent fluid. Administered as: Various dilutions (see below). Specific Gravity: 0.88 g/ml. Solubility: 6% in water. Storage: At ambient temperature in the dark. Stability: Stable up to 200°C.

Method

Species / strain
Species / strain / cell type:
other: Salmonella/ mammalian-microsome bacterial mutagenicity assay. Strains TA98, TA100, TA1535, TA1537.
Metabolic activation:
with and without
Metabolic activation system:
S9 rat liver homogenate (aroclor 1254 induced)
Test concentrations with justification for top dose:
5.0, 15.8, 50, 158, 500, 1580, 5000 µg/plate
Vehicle / solvent:
none (test material solutions were prepared in distilled 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/+S9); 2-nitrofluorene (TA98/-S9); sodium azide (TA100, TA1535/-S9); ICR-191 (TA1537/-S9)
Details on test system and experimental conditions:
METHOD OF APPLICATION: preincubation

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

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

DETERMINATION OF CYTOTOXICITY
- Method: bacterial background lawn evaluation
- no cytotoxcity observed
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 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

PnB did not cause mutations in the Ames plate assay with or without S-9 metabolic activation. Hence, the test material was classified as negative in the Ames test under the experimental conditions used.
Executive summary:

Propylene 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 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.

Based upon the results in TA100, the top five concentrations were repeated in TA98, 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 Ames under the experimental conditions used.