2-methylanisole

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Based on the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the five closest read across substances, gene mutation was predicted for 2- Methylanisole. The study assumed the use of Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102 with S9 metabolic activation system. 2- Methylanisole was predicted to not induce gene mutation in Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102 in the presence of S9 metabolic activation system and hence, according to the prediction made, it is not likely to classify as a gene mutant in vitro.

Based on the predicted result it can be concluded that the substance is considered to not toxic as per the criteria mentioned in CLP regulation.

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:

Prediction model based estimation and data from read across chemicals have been reviewed to determine the mutagenic nature of 2 -Methylanisole. The summary is as mentioned below:

Based on the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the five closest read across substances, gene mutation was predicted for 2- Methylanisole. The study assumed the use of Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102 with and without S9 metabolic activation system. 2- Methylanisole was predicted to not induce gene mutation in Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102 in the presence and absence of S9 metabolic activation system and hence, according to the prediction made, it is not likely to classify as a gene mutant in vitro.

Gene mutation toxicity study was performed to determine the mutagenic nature of the 70 -80% structurally and functionally simiilar read across chemical Anisole (RA CAS no 100-66 -6) using Salmonella typhimurium LT-2 strains TA 98, TA 100, TA 1535, and TA 1537. The material was dissolved in ethanol and applied at a concentration of 3 µmole/plate in the spot test performed. Anisole is 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 is not likely to classify as gene mutant in vitro.

An in vitro mammalian cell gene mutation study was designed (Sustainability Support Services, 2015) and conducted to determine the genotoxicity profile of 50 -60% structurally similar read across chemical Methyl 2-napthyl ether (RA CAS no 93 -04 -9; 2-methoxynaphthalene) when administered to Chinese Hamster Ovary (CHO) cells. In the genotoxicity test, methyl 2-napthyl ether was administered to CHO cells for 3 hrs at the dose levels of 0, 0.1, 0.25, 0.5 or 1.0 mM and in the absence or presence of exogenous metabolic activation. CHO cells representing the negative controls were exposed to the vehicle. Positive controls, such as N-ethyl-N-nitrosourea (ENU) experiments without metabolic activation and 7,12-dimethylbenz(a) anthracene in experiments with metabolic activation, were also included in each test. The positive control ENU gave a clear indication of gene mutations occurring while no other treatment gave rise to gene toxicity. One very diffuse colony was seen in one well out of four at the concentration of 0.5 mM and in the absence with 4% S9 liver microsomal fraction, and two very diffuse colonies were detected in one well out of four at the concentration of 0.1 mM and in the presence with 4% S9 liver microsomal fraction. These diffuse colonies are not regarded t o be relevant since the three spots were only mildly colored by crystal violet, thus indicating that it were small clusters of apoptotic cells taking their last breath instead of cells surviving the TG-selection. This is further supported by the results of the higher tested concentrations of methyl 2-napthyl ether, i.e. these concentrations did not show any evidence of diffuse or clear colonies present. When the mutation frequency was determined, a frequency of 5.35 x 10 ^-4 was shown after a 3 hour exposure of ENU as the positive control and in the absence of S9 liver microsomal fraction. Since no other tested concentration of methyl 2-napthyl ether in the absence or presence of S9 liver microsomal fraction resulted in colonies, we conclude that methyl 2-napthyl ether does not give rise to gene mutations when CHO cells are exposed in vitro to the test chemical at 0, 0.1, 0.25, 0.5 or 1.0 mM for 3 hrs.

In yet another study performed bu Zeiger et al (Environmantal and Molecular Mutagenesis, 1992) for structurally and functionally similar read across chemical, Gene mutation toxicity study was performed to determine the mutagenic nature of alpha-Methylstyrene (RA CAS no 98 -83 -9). The study was performed using Salmonella typhimurium strains TA97, TA98, TA100, TA1535 in the presence and absence of S9 metabolic activation system. The chemical was dissolved in DMSO and used at dose levels 0, 1, 3, 10, 33, 100, 333, 1000 or 3333 µg/plate by the preincubation method. The doses were selected on the basis of preliminary dose range finding study and concurrent solvent and positive controls were included in the study. alpha-Methylstyrene did not induce mutation in Salmonella typhimurium strainsTA97, TA98, TA100, TA1535 in the presence and absence of S9 metabolic activation system and hence the chemical is not likely to classify as a gene mutant in vitro.

Based on the data available for the target chemical and its read across, 2 -Methylanisole 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

Based on the data available for the target chemical and its read across, 2 -Methylanisole (CAS no 578 -58 -5) does not exhibit gene mutation in vitro. Hence the test chemical is not likely to classify as a gene mutant in vitro.