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Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Gene toxicity in vitro study was conducted on theSalmonella typhimuriumstrains TA100 and TA98 for the test chemical 2, 3 Dimethylphenol. The study was performed by the plate incorporation assay to evaluate the toxic nature during the 2 days incubation period at a dose level of 10-20 mg/mL (10000- 20000 µg/mL) in the presence and absence of S9 metabolic activation system.The test compound 2, 3 Dimethylphenol did not induce gene mutation in the Salmonella typhimurium strains TA100 and TA98 in the presence and absence of S9 metabolic activation system by the reversion assay and hence the test chemical is not likely to classify as a gene mutant in vitro.

Link to relevant study records
Reference
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:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Justification for type of information:
Data is from peer reviewed journal
Qualifier:
according to guideline
Guideline:
other: Refer below principle
Principles of method if other than guideline:
Gene mutation toxiicty studywas performed to determine the mutagenic nature of 2, 3 Dimethylphenol usingin Salmonella typhimurium strains TA100 and TA98
GLP compliance:
not specified
Type of assay:
bacterial gene mutation assay
Specific details on test material used for the study:
- Name of test material: 2, 3 Dimethylphenol
- IUPAC name: 2,3-dimethylphenol
- Molecular formula: C8H10O
- Molecular weight: 122.166 g/mol
- Substance type: Organic
- Physical state: solid
- Purity: No data
- Impurities (identity and concentrations): No data available.
Target gene:
Histidine
Species / strain / cell type:
S. typhimurium, other: TA100 and TA98
Details on mammalian cell type (if applicable):
Not applicable
Additional strain / cell type characteristics:
not applicable
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:
10-20 mg/ml (10000- 20000 µg/mL)
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: The chemical is soluble in DMSO
Untreated negative controls:
not specified
Negative solvent / vehicle controls:
yes
Remarks:
DMSO
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)

DURATION
- Preincubation period: No data available
- Exposure duration: 2 days
- Expression time (cells in growth medium): 2 days
- Selection time (if incubation with a selection agent): No data available
- Fixation time (start of exposure up to fixation or harvest of cells): No data available

SELECTION AGENT (mutation assays): No data available
SPINDLE INHIBITOR (cytogenetic assays): No data available
STAIN (for cytogenetic assays): No data available

NUMBER OF REPLICATIONS: No data available

NUMBER OF CELLS EVALUATED: No data available

DETERMINATION OF CYTOTOXICITY
- Method: mitotic index; cloning efficiency; relative total growth; other: No data available

OTHER EXAMINATIONS:
- Determination of polyploidy: No data available
- Determination of endoreplication: No data available
- Other: No data available

OTHER: No data available
Rationale for test conditions:
No data
Evaluation criteria:
Reversion of histidine-requiring auxotrophs of Salmonella typhimurium
Statistics:
No data available
Species / strain:
S. typhimurium, other: TA100 and TA98
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not specified
Vehicle controls validity:
valid
Untreated negative controls validity:
not specified
Positive controls validity:
not specified
Additional information on results:
No data available
Conclusions:
The test compound 2, 3 Dimethylphenol did not induce gene mutation in the Salmonella typhimurium strains TA100 and TA98 in the presence and absence of S9 metabolic activation system by the reversion assay and hence the test chemical is not likely to classify as a gene mutant in vitro.
Executive summary:

Gene toxicity in vitro study was conducted on the Salmonella typhimurium strains TA100 and TA98 for the test chemical 2, 3 Dimethylphenol. The study was performed by the plate incorporation assay to evaluate the toxic nature during the 2 days incubation period at a dose level of 10-20 mg/mL (10000- 20000 µg/mL) in the presence and absence of S9 metabolic activation system. The test compound 2, 3 Dimethylphenol did not induce gene mutation in the Salmonella typhimurium strains TA100 and TA98 in the presence and absence of S9 metabolic activation system by the reversion assay and hence the test chemical is not likely to classify as a gene mutant in vitro.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Genetic toxicity in vitro:

Various peer reviewed publications were reviewed to determine the mutagenic nature of 2, 3 dimethylphenol. The studies are as mentioned below:

Gene toxicity in vitro study was conducted by Epler et al ( Environmental Health Perspectives, 1979) on the Salmonella typhimurium strains TA100 and TA98 for the test chemical 2, 3 Dimethylphenol (RA CAS no 526 -75 -0). The study was performed by the plate incorporation assay to evaluate the toxic nature during the 2 days incubation period at a dose level of 10-20 mg/mL (10000- 20000 µg/mL) in the presence and absence of S9 metabolic activation system.The test compound 2, 3 Dimethylphenol did not induce gene mutation in the Salmonella typhimurium strains TA100 and TA98 in the presence and absence of S9 metabolic activation system by the reversion assay and hence the test chemical is not likely to classify as a gene mutant in vitro.

In another study by Florin et al (Toxicology, 1980) Gene mutation toxicity study was performed to determine the mutagenic nature of the test compound 2,3 Dimethylphenol (CAS no 526 -75 -0). The material was dissolved in ethanol and applied at a concentration of 3 µmole/plate in the spot test performed to Salmonella typhimurium LT-2 strains TA 98, TA 100, TA 1535, and TA 1537 with and without S9 metabolic activation system. 2,3 Dimethylphenol did not induce reversion of mutant strains and henceis not mutagenic in the bacterium Salmonella typhimurium LT-2 strains TA 98, TA 100, TA 1535, and TA 1537 with and without S9 metabolic activation system and hence the chemical is not likely to classify as gene mutant in vitro.

Jansson et al (Mutation research, 1986) performed in vitro Sister-chromatid exchange analysis was performed to evaluate the mutagenic nature of the test compound 2, 3 Dimethylphenol. The test chemical was used at a concentration of 0-0.5mM.Blood from healthy non-smoking donors was centrifuged (250 × g) to remove the erythrocytes and the supernatant was collected. The lymphocyte fraction thus obtained was grown in Medium 199 with Earles salt. The cultures contained 25% autologous serum, 1.25% phytohaemagglutinin and 0.1 mM 5-bromodeoxyuridine. After 24 h incubation at 37°C, the fractions or compounds to be tested were added to the cultures. After 88-90 h, the cells were treated consecutively with colchicine and hypotonic KC1 and they were then fixed in methanol/acetic acid (3 : 1) for 1 h. After the culture time used, the portion of cells that have divided more than 2 times is about 20-30%. Chromosome preparations were made by applying the cell suspension to wet cooled slides. The staining procedure was mainly according to Wolff and Perry. The slides were stained with Hoechst dye for 12 min and then rinsed in Mcllvaines buffer. They were then exposed to UV-light for 10 min, incubated in 0.3 M NaCI/0.3 M sodium citrate for 2 h at 60°C and stained with Giemsa dye for 20 min. The lymphosytes were observed for their SCE inbducing effects. The test compound 2, 3 Dimethylphenol did not induce sister chromatid exchange in the human lymphocytes and hence the chemical is not likely to classify as a gene mutant in vitro.

Based on the information available for the target chemical, 2,3 dimethylphenol does not exhibit gene mutation in vitro. Hence the test chemical is not likely to classify as a gene mutant in vitro.

Justification for classification or non-classification

On the basis of available data, the test material is not likely to classify as a mutagen in vitro.