Propan-1-ol

Genetic toxicity: in vitro

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2009

Report date:

2009

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

Test material information

Constituent 1

Reference substance name:

Propan-1-ol

EC Number:

200-746-9

EC Name:

Propan-1-ol

Cas Number:

71-23-8

Molecular formula:

C3H8O

IUPAC Name:

propan-1-ol

Test material form:

liquid

Specific details on test material used for the study:

- Name of test material (as cited in study report): N-Propanol
- Physical state: Liquid, colorless, clear
- Analytical purity: 99.95 area-%
- Lot/batch No.: TK504_20081022
- Storage condition of test material: Room temperature

Method

Target gene:

S. typhimurium: his-
E. coli: trp-

Species / strain

Species / strain 1

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Species / strain 2

Species / strain / cell type:

E. coli WP2 uvr A

Metabolic activation:

with and without

Metabolic activation system:

liver S9 mix from phenobarbital i.p. and β-naphthoflavone orally induced rats

Test concentrations with justification for top dose:

0; 20; 100; 500; 2500 and 5000 μg/plate (SPT)
0; 312.5; 625; 1250; 2500 and 5000 μg/plate (PIT)

Vehicle / solvent:

water

Controls

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: see "Details on test system"

Details on test system and experimental conditions:

Experiment 1: Standard plate test (SPT)
Test tubes containing 2 mL soft agar kept in a water bath at 45°C, and remaining components added in the following order:
0 .1 mL test solution or vehicle
0 .1 mL bacterial suspension
0 .5 mL S-9 mix (in tests with metabolic activation) or 0 .5 mL phosphate buffer (in tests without metabolic activation).
After mixing, the samples are poured onto Vogel-Bonner agar plates.

Experiment 2: Preincubation assay (PIT)
0.1 mL test solution or vehicle, 0.1 mL bacterial suspension and 0 .5 mL S-9 mix are
incubated at 37°C for the duration of 20 minutes. Subsequently, 2 mL of soft agar is added
and, after mixing, the samples are poured onto the Vogel-Bonner agar plates.

Experiment1&2
In each experiment 3 test plates per dose or per control used; after incubation at 37°C for 48 hours in the dark, the bacterial colonies ( his+/trp+ revertants) are counted.
Positive control:
with metabolic activation: 2-aminoanthracene: 2.5 μg/plate for each S. typhimurium strain; 60 μg/plate for E. coli WP2 uvrA
without metabolic activation: 5 μg/plate N-methyl-N'-nitro-N-nitrosoguanidine for TA 100 and TA 1535, 10 μg/plate 4-nitro-o-phenylendiamine
for TA 98, 100 μg/plate 9-aminoacridine chloride for TA 1537 and 5 µg/plate N-Ethyl-N-nitro-N-nitrosoguanidine for E. coli WP2 uvrA; all substances were dissolved in DMSO.
The titer was determined and in regularly measurements the strain characteristics were checked. Sterility control was performed.

Evaluation criteria:

Acceptance criteria
Generally, the experiment is considered valid if the following criteria are met:
• The number of revertant colonies in the negative controls was within the range of the historical negative control data for each tester strain.
• The sterility controls revealed no indication of bacterial contamination.
• The positive control substances both with and without S9 mix induced a distinct increase in the number of revertant colonies within the range of the historical positive control data or above.
• The titer of viable bacteria was ≥ 10e8/mL.

Assessment criteria
The test chemical is considered positive in this assay if the following criteria are met:
• A dose-related and reproducible increase in the number of revertant colonies, i.e. about doubling of the spontaneous mutation rate in at least one tester strain either without S9 mix or after adding a metabolizing system.
A test substance is generally considered non-mutagenic in this test if:
• The number of revertants for all tester strains were within the historical negative control range under all experimental conditions in at least two experiments carried out independently of each other.

Results and discussion

Test results

Species / strain:

other: S. typhimurium TA 1535, TA 100, TA 1537, TA 98 and E. coli WP2 uvrA

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

Additional information on results:

No precipitation of the test substance was found with and without S9 mix.

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

Mutagenicity

Standard plate test (20 - 5000 µg/plate)
Strain	Metabolic activation system	mean revertants in Controls	maximum revertant factor	dose dependency	Assessment
TA 98	no	28	1.0	no	negative
	yes	33	1.2	no	negative
TA 100	no	100	1.1	no	negative
	yes	99	1.3	no	negative
TA 1535	no	17	1.0	no	negative
	yes	15	1.0	no	negative
TA 1537	no	11	1.3	no	negative
	yes	9	1.4	no	negative
WP2 uvr A	no	34	1.1	no	negative
	yes	39	1.1	no	negative
Preincubation test (312.5 - 5000 µg/plate)
Strain	Metabolic activation system	mean revertants in Controls	maximum revertant factor	dose dependency	Assessment
TA 98	no	26	1.1	no	negative
	yes	32	1.0	no	negative
TA 100	no	102	1.0	no	negative
	yes	103	1.1	no	negative
TA 1535	no	14	1.0	no	negative
	yes	14	1.0	no	negative
TA 1537	no	8	1.0	no	negative
	yes	8	1.0	no	negative
WP2 uvr A	no	36	1.1	no	negative
	yes	51	1.0	no	negative