2,3,5-trimethylphenol

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Gene mutation toxicity study was performed to determine the mutagenic nature of the test compound 2,3,5 Trimethylphenol. The material was dissolved in ethanol and applied at a concentration of 0 or 3 µmole/plate in the spot test performed. The plates were observed for an increase in the number of spontaneous revertants. 2,3,5 Trimethylphenol did not induce an increase in the number of spontaneous revertants and hence is not mutagenic in the bacterium Salmonella typhimurium LT-2 strains TA98, TA100, TA1537 and TA1535 with and without S9 metabolic activation system and hence is not likely to classify as gene mutant in vitro.

Link to relevant study records

Reference

Endpoint:

in vitro gene mutation study in bacteria

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 publication

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Principles of method if other than guideline:

Gene mutation toxicity study was performed to determine the mutagenic nature of the test compound 2,3,5 Trimethylphenol by performing Spot test

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Specific details on test material used for the study:

- Name of test material: 2,3,5 Trimethylphenol
- IUPAC name: 2,3,5 Trimethylphenol
- Molecular formula: C9H12O
- Molecular weight: 136.193 g/mol
- Substance type: Organic
- Physical state: Solid
- Purity: No data available
- Impurities (identity and concentrations): No data available

Target gene:

Histidine

Species / strain / cell type:

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

Remarks:

LT2 strains

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:

Liver fraction (S-9) from Aroclor 1254 or methylcholanthrene induced rats

Test concentrations with justification for top dose:

0 or 3 µmole/plate

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: Ethanol
- Justification for choice of solvent/vehicle: The chemical was soluble in ethanol

Untreated negative controls:

not specified

Negative solvent / vehicle controls:

not specified

True negative controls:

not specified

Positive controls:

not specified

Positive control substance:

other: N-methyl-N'-nitro-N-nitrosoguanidin (without metabolic activation) and 2-aminoanthracene (with activation)

Details on test system and experimental conditions:

METHOD OF APPLICATION: Spot test (in agar)

DURATION
- Preincubation period: No data available
- Exposure duration: No data available
- Expression time (cells in growth medium): No data available
- 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:

1. Increase in the number of spontaneous revertants
2. The presence of the rfa-mutation was checked by crystal violet inhibition;
3. The presence of the plasmid pKM 101 in strains TA 98 and TA 100 was checked by resistance to ampicillin

Statistics:

No data

Species / strain:

S. typhimurium, other: LT-2 strains TA 98, TA 100, TA1535 and TA1537

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

not specified

Untreated negative controls validity:

not specified

Positive controls validity:

valid

Additional information on results:

No data available

Conclusions:

2,3,5 Trimethylphenol is not mutagenic in the bacterium Salmonella typhimurium LT-2 strains TA98, TA100, TA1535 and TA1537 with and without S9 metabolic activation system and hence is not likely to classify as gene mutant in vitro.

Executive summary:

Gene mutation toxicity study was performed to determine the mutagenic nature of the test compound 2,3,5 Trimethylphenol

 

The material was dissolved in ethanol and applied at a concentration of 0 or 3 µmole/plate in the spot test performed. The plates were observed for an increase in the number of spontaneous revertants

 

2,3,5 Trimethylphenol did not induce an increase in the number of spontaneous revertants and hence is not mutagenic in the bacterium Salmonella typhimurium LT-2 strains TA98, TA100, TA1537 and TA1535 with and without S9 metabolic activation system and hence is not likely to classify as 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

Gene mutation in vitro:

Peer reviewed publication was reviewed to determine the mutagenic nature of 2,3,5 Trimethylphenol (IUPAC name: 2,3,5 Trimethylphenol). The studies are as mentioned below:

Gene mutation toxicity study was performed to determine the mutagenic nature of the test compound 2,3,5 Trimethylphenol. The material was dissolved in ethanol and applied at a concentration of 0 or 3 µmole/plate in the spot test performed. The plates were observed for an increase in the number of spontaneous revertants. 2,3,5 Trimethylphenol did not induce an increase in the number of spontaneous revertants and hence is not mutagenic in the bacterium Salmonella typhimurium LT-2 strains TA98, TA100, TA1537 and TA1535 with and without S9 metabolic activation system and hence is not likely to classify as gene mutant in vitro.

Epler et al (Environmental Health Perspectives, 1979) performed gene mutation toxicity in vitro study on the Salmonella typhimurium strains TA100 and TA98 for structurally and fuctionally similar read across chemical 2, 3 Dimethylphenol (RA CAS no 526 -75 -0; IUPAC name: 2, 3 Dimethylphenol) in the presence and absence of S9 metabolic activation system. Plate incorporation assay was performed to evaluate the toxic nature during the 2 days incubation period at a dose level of 10-20 mg/mL (10000- 20000 µg/mL). Concurrent solvent and positive controls were also included in the study.2, 3 Dimethylphenol did not induce reversion of mutations in the Salmonella typhimurium strains TA100 and TA98 both in the presence and absence of S9 metabolic activation system and hence is not likely to classify as a gene mutant in vitro.

Tayama et al ( Mutation Research, 2008) performed gene mutation study to evaluate the mutagenic nature of the structurally and functionally similar read across chemcal p-nonylphenol (RA CAS no 104 -40 -5 ; IUPAC name: 4-nonylphenol). About 6×10⁵cells were seeded into tissue-culture flasks containing 10 ml of medium and cultured. After 48 h, 5ml of medium containing each chemical were added, and the culture was incubated for 3 h and then washed. Ten milliliters of medium containing 5-bromo-2-deoxyuridine at a final concentration of 0.5 µg/ml was added, and the cultures were incubated in the dark for 27 h (two rounds of replication), after which they were harvested. Two hours before harvesting, colcemid was added to the medium at a final concentration of 0.1 µg/ml. The cell-cycle delay, which is recognized by the metaphases without differently staining sister-chromatids (DSC), those are first division cells, was also examined as an indicator of cytotoxic effects. Characteristic c-mitotic-like chromosome figures that were extremely contracted and spread chromatids in metaphase were noticed during the observation of CAs. For CA and DSC, 100 metaphases were observed; for ERD and c-mitosis like changes, 200 metaphases were observed. To assess the statistical significance, Chi-square test was performed for CA and ERD. p-nonylphenol failed to induce chromosomal aberration (gaps, breaks, and exchanges) in CHO-K1 cells and hence is negative for gene mutation in vitro.

 

Based on the information available for the test chemical and its read across, 2,3,5 Trimethylphenol does not exhibit gene mutation in vitro. Hence the chemical is not likely to classify as a gene mutant in vitro as per the criteria mentioned in CLP regulation.

Justification for classification or non-classification

Based on the information available for the test chemical and its read across, 2,3,5 Trimethylphenol (IUPAC name: 2,3,5 Trimethylphenol) does not exhibit gene mutation in vitro. Hence the chemical is not likely to classify as a gene mutant in vitro as per the criteria mentioned in CLP regulation.