Methyl isonicotinate

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

In Vitro genetic toxicity study for Methyl Isonicotinate was assessed for its possible mutagenic potential. For this purpose Bacterial reverse mutation assay was performed in Salmonella typhimurium strains TA1537, TA2637, TA98, TA97a and TA100. Plate incorporation method was used. The examination with TA97a was unsuccessful because bacteria did not grow on Tris minimal agar.No mutagenic effects were observed in all other strain.. Therefore Methyl Isonicotinate was considered to non mutagenic in Salmonella typhimurium strains TA1537, TA2637, TA98 and TA100. Hence the substance cannot be classified 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:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Justification for type of information:

Data is from publication

Qualifier:

according to guideline

Guideline:

other: As mention below

Principles of method if other than guideline:

To evaluate the mutagenic potential of Methyl Isonicotinate in Salmonella typhimurium LT2 strains TA1537, TA2637, TA97a, TA98 and TA100 by Bacterial reverse mutation assay.

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Specific details on test material used for the study:

- Name of test material (as cited in study report): Methyl isonicotinate
- Molecular formula (if other than submission substance): C7H7NO2
- Molecular weight (if other than submission substance): 137.1373 g/mole
- Substance type: Organic
- SMILES:COC(=O)c1ccncc1
- InChI: 1S/C7H7NO2/c1-10-7(9)6-2-4-8-5-3-6/h2-5H,1H3

Target gene:

Histidine

Species / strain / cell type:

S. typhimurium, other: TA1537, TA2637, TA97a, TA98 and TA100

Details on mammalian cell type (if applicable):

Not applicable

Additional strain / cell type characteristics:

not specified

Cytokinesis block (if used):

not specified

Metabolic activation:

not specified

Test concentrations with justification for top dose:

not specified

Vehicle / solvent:

not specified

Untreated negative controls:

not specified

Negative solvent / vehicle controls:

not specified

True negative controls:

not specified

Positive controls:

not specified

Details on test system and experimental conditions:

Details on test system and conditions
METHOD OF APPLICATION: in agar (plate incorporation)

Rationale for test conditions:

not specified

Evaluation criteria:

Number of Histidine revertants per plate was observed.

Statistics:

not specified

Species / strain:

S. typhimurium, other: TA1537, TA2637, TA98 and TA100

Metabolic activation:

not specified

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

not specified

Untreated negative controls validity:

not specified

Positive controls validity:

not specified

Remarks on result:

other: No mutagenic effect were observed

Conclusions:

Methyl Isonicotinate (2459-09-8) was evaluated for its mutagenic potential in Salmonella typhimurium strains TA1537, TA2637, TA98 and TA100. The test result was considered to be negative for Bacterial reverse mutation assay.

Executive summary:

In Vitro genetic toxicity study for Methyl Isonicotinate was assessed for its possible mutagenic potential. For this purpose Bacterial reverse mutation assay was performed in Salmonella typhimurium strains TA1537, TA2637, TA98, TA97a and TA100. Plate incorporation method was used. The examination with TA97a was unsuccessful because bacteria did not grow on Tris minimal agar.No mutagenic effects were observed in all other strain.. Therefore Methyl Isonicotinate was considered to non mutagenic in Salmonella typhimurium strains TA1537, TA2637, TA98 and TA100. Hence the substance cannot be classified 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

Genetic toxicity in vitro

Experimental study, Prediction model based estimation and data from read across chemical have been reviewed to determine the mutagenic nature of Methyl Isonicotinate (2459-09-8). The studies are as mentioned below

For target substance an experimental study was conducted by H. Iyehara Ogawaet al.( Mutation Research, 1988) to determine its mutagenicnature. In Vitro genetic toxicity study for Methyl Isonicotinate was assessed for its possible mutagenic potential. For this purpose Bacterial reverse mutation assay was performed in Salmonella typhimurium strains TA1537, TA2637, TA98, TA97a and TA100. Plate incorporation method was used. The examination with TA97a was unsuccessful because bacteria did not grow on Tris minimal agar.No mutagenic effects were observed in all other strain.. Therefore Methyl Isonicotinate was considered to non mutagenic in Salmonella typhimurium strains TA1537, TA2637, TA98 and TA100. Hence the substance cannot be classified as gene mutant in vitro.

Gene mutation toxicity was predicted for Methyl Isonicotinate (2459-09-8) using the battery approach from Danish QSAR database (2017). The study assumed the use of Salmonella typhimurium bacteria in the Ames test. The end point for gene mutation has been modeled in the Danish QSAR using the three software systems Leadscope, CASE Ultra and SciQSAR. Based on predictions from these three systems, a fourth and overall battery prediction is made. The battery prediction is made using the so called Battery algorithm. With the battery approach it is in many cases possible to reduce “noise” from the individual model estimates and thereby improve accuracy and/or broaden the applicability domain. Gene mutation toxicity study as predicted by Methyl Isonicotinate is negative and hence the chemical is predicted to not classify as a gene mutant in vitro.

In a study for structurally and functionally similar read across chemical, Gene mutation toxicity study was performed by Errol Zeigeret.al. (Environmental and Molecular Mutagenesis, 1992) to determine the mutagenic nature of Methyl benzoate (93-58-3). The read across substances share high similarity in structure and log kow .Therefore, it is acceptable to derive information on mutation from the analogue substance. Gene mutation toxicity study was performed to determine the mutagenic nature of methyl benzoate. The study was performed using Salmonella typhimurium strains TA97, TA98, TA100, TA1535, TA1537 in the presence and absence of S9 metabolic activation system. The chemical was dissolved in DMSO and used at dose levels 0, 10, 33, 100, 333, 666, 1000, 1666, 3333 or 6666 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. The plates were observed for a dose dependent increase in the number of Histidine- independent (his+) colonies. Methyl benzoate did not induce mutation in Salmonella typhimurium strains TA97, TA98, TA100, TA1535, TA1537 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.

In a study for structurally and functionally similar read across chemical, Gene mutation toxicity study was performed by National Institute of Technology and Evaluation (Japan chemicals collaborative knowledge database , 2017)to determine the mutagenic nature of Dimethyl naphthalene-2,6-dicarboxylate (840-65-3). The read across substances share high similarity in structure and log kow .Therefore, it is acceptable to derive information on mutation from the analogue substance. Genetic toxicity in vitro study was assessed for Dimethyl naphthalene-2,6-dicarboxylate . For this purpose AMES test was performed according to Guidelines for Screening Mutagenicity Testing of Chemicals (Japan) and OECD Guideline No. 471 and 472.The test material was exposed to Salmonella typhimurium, TA100, TA1535, TA98, TA1537, Escherichia coli WP2 uvrA in the presence and absence of metabolic activation S9. The concentration of test material used in the presence of metabolic activation were 0, 313 - 5000µg/plate. While in the absence of metabolic activation the concentration were 0, 313, 625, 1250, 2500, 5000µg/plate. No mutagenic effects were observed in all strains, in the presence and absence of metabolic activation. Therefore Dimethyl naphthalene-2,6-dicarboxylate was considered to be non mutagenic in Salmonella typhimurium, TA100, TA1535, TA98, TA1537,Escherichia coli WP2 uvrA by AMES test. Hence the substance cannot be classified as gene mutant in vitro.

Based on the data available for the target chemical and its read across substance and applying weight of evidence Methyl Isonicotinate (2459-09-8) 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

Thus based on the above annotation and CLP criteria for the target chemical . Methyl Isonicotinate (2459-09-8) does not exhibit gene mutation in vitro. Hence the test chemical is not likely to classify as a gene mutant in vitro.