Methyl 3-mercaptopropionate

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

Study period:

N/A to 1983-03-08

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study conducted with methods similar to OECD guideline 471. However, an E. coli strain or S. typhimurium strain TA102 was not included.

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1983

Report date:

1983

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Remarks:

An E. coli strain or S. typhimurium strain TA102 was not included.

Principles of method if other than guideline:

N/A

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Methyl 3-mercaptopropionate

EC Number:

220-912-4

EC Name:

Methyl 3-mercaptopropionate

Cas Number:

2935-90-2

Molecular formula:

C4H8O2S

IUPAC Name:

methyl 3-sulfanylpropanoate

Details on test material:

- Name of test material (as cited in study report): methyl 3-mercaptopropionate
- Molecular formula (if other than submission substance): N/A
- Molecular weight (if other than submission substance): N/A
- Smiles notation (if other than submission substance): N/A
- InChl (if other than submission substance): N/A
- Structural formula attached as image file (if other than submission substance): N/A
- Substance type: active
- Physical state: liquid

Method

Target gene:

histidine locus

Species / strain

Species / strain / cell type:

S. typhimurium, other: TA1538, TA1537, TA1535, TA98 and TA100

Details on mammalian cell type (if applicable):

N/A

Additional strain / cell type characteristics:

other: See below for additional strain characteristics.

Metabolic activation:

with and without

Metabolic activation system:

Aroclor 1254 induced rat liver S9

Test concentrations with justification for top dose:

61.7, 185.2, 555.6, 1666.7 and 5000 ug/plate

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: The test substance was freely soluble in DMSO.

Controls

Controls 1

Untreated negative controls:

yes

Remarks:

untreated

Negative solvent / vehicle controls:

yes

Remarks:

DMSO (vehicle of the test substance)

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: Methylnitronitrosoguanidine- used for TA1535 and TA100 at 5 ug/plate

Remarks:

without metabolic activation

Controls 2

Untreated negative controls:

yes

Remarks:

untreated

Negative solvent / vehicle controls:

yes

Remarks:

DMSO (vehicle of the test substance)

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 2-aminoanthracene-used for all strains at 5 ug/plate

Remarks:

with metabolic activation

Controls 3

Untreated negative controls:

yes

Remarks:

untreated

Negative solvent / vehicle controls:

yes

Remarks:

DMSO (vehicle of the test substance)

True negative controls:

no

Positive controls:

yes

Positive control substance:

9-aminoacridine

Remarks:

without metabolic activation

Migrated to IUCLID6: used for TA1537 at 75 ug/plate

Controls 4

Untreated negative controls:

yes

Remarks:

untreated

Negative solvent / vehicle controls:

yes

Remarks:

DMSO (vehicle of the test substance)

True negative controls:

no

Positive controls:

yes

Positive control substance:

2-nitrofluorene

Remarks:

without metabolic activation

Migrated to IUCLID6: used for TA1538 and TA98 at 50 ug/plate

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation)


DURATION
- Preincubation period: N/A
- Exposure duration: ~ 2 days (Contents were poured onto VBE minimal agar plates, gently rotated and tilted to assure uniform distribution of the top agar, allowed to harden on an even surface for one hour, and inverted and put in a dark 37 +/- 0.5 deg. C incubator.)
- Expression time (cells in growth medium): N/A
- Selection time (if incubation with a selection agent): N/A
- Fixation time (start of exposure up to fixation or harvest of cells): N/A


SELECTION AGENT (mutation assays): N/A
SPINDLE INHIBITOR (cytogenetic assays): N/A
STAIN (for cytogenetic assays): N/A


NUMBER OF REPLICATIONS: 3


NUMBER OF CELLS EVALUATED: N/A


DETERMINATION OF CYTOTOXICITY
- Method: measurement of the bacterial background lawn


OTHER EXAMINATIONS:
- Determination of polyploidy: N/A
- Determination of endoreplication: N/A
- Other: N/A


OTHER:
Spontaneous revertant frequencies were determined and had to be within acceptable limits for each study. The presence of the specific genetic markers were determined periodically for each tester strain. Each organism was routinely checked for: 1) histidine requirement, 2) biotin requirement (for uvrB deletion), 3) sensitivity to crystal violet and/or deoxycholate (for deep rough (rfa) mutation to cell wall), and 4) ampicillin resistant R factor (for tester strains TA100 and TA98). Each new batch of S9 was checked with standard mutagens to evaluate its strength and to find the optimum amount to use for general screening.

Evaluation criteria:

For the test to be considered valid, the following conditions were required:
1: Demonstration of toxicity of the test substance for the tester strains, unless this was not possible due to limited solubility of the test substance.
2: The negative control responses were within the normal range of the laboratory database.
3. Confirmation of sensitivity and responsiveness of the tester strains to mutagenic action as indicated by their responses to the positive controls.
If the above criteria were met, the test substance was considered to be mutagenic if it induced a positive response in a dose-related manner over three concentrations, with the baseline increase in the number of histidine revertants equal to twice the solvent control level.

Statistics:

N/A

Results and discussion

Test results

Species / strain:

S. typhimurium, other: TA1538, TA1537, TA1535, TA98 and TA100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

TEST-SPECIFIC CONFOUNDING FACTORS
- Effects of pH: N/A
- Effects of osmolality: N/A
- Evaporation from medium: N/A
- Water solubility: N/A
- Precipitation: N/A
- Other confounding effects: N/A


RANGE-FINDING/SCREENING STUDIES:
Dose levels for the mutagenicity test were determined in a range-finding (toxicity) study. 2 mL of complete top agar, 0.1 mL of an overnight culture of TA100 and 0.1 mL of various concentrations of the test substance in the absence of metabolic activation were combined. The contents of the tube were thoroughly mixed, poured and uniformly distributed over VBE minimal agar. The plates were allowed to harden approximately one hour, inverted and put into a dark 37+/-0.5 degrees C incubator. After two days, the background lawn of growth and revertant colonies in both test and control plates were scored. Observations of test substance precipitation were similarly recorded. The maximum dose selected for the mutagenicity test was 5,000 ug/plate because it exhibited growth inhibition. No further details on concentrations used or results of the range-finding study were provided.


COMPARISON WITH HISTORICAL CONTROL DATA: N/A


ADDITIONAL INFORMATION ON CYTOTOXICITY:
The test substance was cytotoxic at 5000 ug/plate in both the presence and absence of metabolic activation in all strains, except in strain TA98 in the presence of metabolic activation.

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

The test substance in the presence and absence of metabolic activation did not increase the reversion rate of any of the strains, and was therefore considered not to be mutagenic in the test system.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative with and without metabolic activation

The test substance was evaluated for mutagenic potential in the absence and presence of metabolic activation using the Ames test. Under the conditions of the study, the test substance was determined to be non-mutagenic up to a dose level of 5000 ug/plate.

Executive summary:

N/A