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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:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Justification for type of information:
Data is from NTRL report

Data source

Reference
Reference Type:
secondary source
Title:
Summary of toxicity studies for 4-METHOXYPHENYLACETIC ACID (MPAA)
Author:
National Technical Information Service
Year:
1991
Bibliographic source:
National Technical Information Service, OTS0530656-1 (1991)

Materials and methods

Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
Ames test was performed to test the mutagenic capability of 4- Methoxyphenylacetic acid
GLP compliance:
not specified
Type of assay:
bacterial gene mutation assay

Test material

Constituent 1
Reference substance name:
4-MethoxyphenyIacetic Acid (MPAA)
IUPAC Name:
4-MethoxyphenyIacetic Acid (MPAA)
Constituent 2
Chemical structure
Reference substance name:
4-methoxyphenylacetic acid
EC Number:
203-166-4
EC Name:
4-methoxyphenylacetic acid
Cas Number:
104-01-8
Molecular formula:
C9H10O3
IUPAC Name:
(4-methoxyphenyl)acetic acid
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Name of test material (as cited in study report): 4-methoxyphenylacetic acid
- Molecular formula (if other than submission substance): C9-H10-O3
- Molecular weight (if other than submission substance): 166.175
- Smiles notation (if other than submission substance): c1(ccc(OC)cc1)CC(O)=O
- InChl (if other than submission substance): 1S/C9H10O3/c1-12-8-4-2-7(3-5-8)6-9(10)11/h2-5H, 6H2, 1H3, (H,10,11)
- Substance type: Organic
- Physical state: Solid
Specific details on test material used for the study:
- Name of the test material: 4-methoxyphenyl)acetic acid
- Molecular formula: C9H10O3
- Molecular weight: 166.175 g/mol
- Substance type: Organic
- Purity: No data

Method

Target gene:
Histidine
Species / strain
Species / strain / cell type:
S. typhimurium, other: Strains not specified
Remarks:
Five tester strains were used
Details on mammalian cell type (if applicable):
Not applicable
Additional strain / cell type characteristics:
not specified
Cytokinesis block (if used):
No data
Metabolic activation:
with and without
Metabolic activation system:
S9 metabolic activation system
Test concentrations with justification for top dose:
100-10,000 µg/plate
Vehicle / solvent:
No data
Controls
Untreated negative controls:
yes
Negative solvent / vehicle controls:
not specified
True negative controls:
not specified
Positive controls:
yes
Positive control substance:
not specified
Details on test system and experimental conditions:
METHOD OF APPLICATION: in agar (plate incorporation)
- Cell density at seeding (if applicable): Not applicable

DURATION
- Preincubation period: No data
- Exposure duration:No data
- Expression time (cells in growth medium): No data
- Selection time (if incubation with a selection agent): No data
- Fixation time (start of exposure up to fixation or harvest of cells): No data

SELECTION AGENT (mutation assays): No data

SPINDLE INHIBITOR (cytogenetic assays): No data

STAIN (for cytogenetic assays): No data

NUMBER OF REPLICATIONS: Triplicate

METHODS OF SLIDE PREPARATION AND STAINING TECHNIQUE USED: No data

NUMBER OF CELLS EVALUATED: No data

NUMBER OF METAPHASE SPREADS ANALYSED PER DOSE (if in vitro cytogenicity study in mammalian cells): No data

CRITERIA FOR MICRONUCLEUS IDENTIFICATION: No data

DETERMINATION OF CYTOTOXICITY
- Method: mitotic index; cloning efficiency; relative total growth; other:
- Any supplementary information relevant to cytotoxicity: No data

OTHER EXAMINATIONS:
- Determination of polyploidy: No data
- Determination of endoreplication: No data
- Methods, such as kinetochore antibody binding, to characterize whether micronuclei contain whole or fragmented chromosomes (if applicable): No data

- OTHER: No data
Rationale for test conditions:
No data
Evaluation criteria:
The plates were observed for a dose dependent increase in the number of revertants/plate
Statistics:
No data

Results and discussion

Test results
Species / strain:
S. typhimurium, other: Strains not specified
Remarks:
Five tester strains were used
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not specified
Vehicle controls validity:
not specified
Untreated negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
TEST-SPECIFIC CONFOUNDING FACTORS
- Effects of pH: No data
- Effects of osmolality: No data
- Evaporation from medium: No data
- Water solubility: No data
- Precipitation: No data
- Definition of acceptable cells for analysis: No data
- Other confounding effects: No data

RANGE-FINDING/SCREENING STUDIES: Preliminary dose range finding study was performed to determine toxicity. The study was performed using Salmonella typhimurium strain TA100 in the presence and absence of S9 metabolic activation system. No toxicity was noted at the mentioned dose level.

CYTOKINESIS BLOCK (if used)
- Distribution of mono-, bi- and multi-nucleated cells: No data

NUMBER OF CELLS WITH MICRONUCLEI
- Number of cells for each treated and control culture: No data
- Indication whether binucleate or mononucleate where appropriate: No data

HISTORICAL CONTROL DATA (with ranges, means and standard deviation and confidence interval (e.g. 95%)
- Positive historical control data: No data
- Negative (solvent/vehicle) historical control data: No data

ADDITIONAL INFORMATION ON CYTOTOXICITY:
- Measurement of cytotoxicity used: No data

Applicant's summary and conclusion

Conclusions:
4 methoxyphenylacetic acid (MPAA) did not exhibit mutagenecity in salmonella typhimurium strains under the test conditions with and without S9 metabolic activation system and hence is not likely to classify as a gene mutant in vitro.
Executive summary:

Ames Salmonella/ Microsome Reverse Mutation test was performed to test the mutagenic activity of 4 -methoxyphenylacetic acid in five Salmonella typhimurium tester strains with five concentrations ranging between 100-10000 µg/plate both in the presence and absence of S9 metabolic activation system. The doses were selected on the basis of dose range finding study to determine toxicity. The preliminary study was performed using Salmonella typhimurium strain TA100 in the presence and absence of S9 metabolic activation system. No toxicity was noted at the mentioned dose level. The main study was performed in triplicate with concurrent negative and positive controls by the plate incorporation protocol. No positive responses were noted in the preliminary and confirmatory mutagenicity studies. 4-methoxyphenylacetic acid (MPAA) did not exhibit mutagenecity in salmonella typhimurium strains under the test conditions with and without metabolic activation system and hence is not likely to classify as a gene mutant in vitro.

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