3-methyl-1-phenylpyrazol-5-ylamine

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 5-Amino-3-methyl-1-phenyl-pyrazol (IUPAC name: 3-methyl-1-phenylpyrazol-5-ylamine). 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. 5-Amino-3-methyl-1-phenyl-pyrazol 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.

Link to relevant study records

Reference

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification

Justification for type of information:

Data is from OECD QSAR Toolbox version 3.3 and the supporting QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: Refer below principle

Principles of method if other than guideline:

Prediction is done using OECD QSAR Toolbox version 3.3, 2017

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Specific details on test material used for the study:

- Name of the test material: 5-Amino-3-methyl-1-phenyl-pyrazol
- IUPAC name: 3-methyl-1-phenylpyrazol-5-ylamine
- Molecular Formula: C10H11N3
- Molecular weight: 173.2179 g/mol
- Substance type: Organic

Target gene:

Histidine

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102

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

Metabolic activation system:

S9 metabolic activation system

Test concentrations with justification for top dose:

No data

Vehicle / solvent:

No data

Untreated negative controls:

not specified

Negative solvent / vehicle controls:

not specified

True negative controls:

not specified

Positive controls:

not specified

Positive control substance:

not specified

Details on test system and experimental conditions:

No data

Rationale for test conditions:

No data

Evaluation criteria:

Prediction was done considering a dose dependent increase in the number of revertants/plate

Statistics:

No data

Species / strain:

S. typhimurium, other: TA 1535, TA 1537, TA 98, TA 100 and TA 102

Metabolic activation:

with

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

Additional information on results:

No data

The prediction was based on dataset comprised from the following descriptors: "Gene mutation"
Estimation method: Takes highest mode value from the 6 nearest neighbours
Domain  logical expression:Result: In Domain

((((("a" or "b" or "c" or "d" )  and "e" )  and "f" )  and "g" )  and ("h" and "i" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Aliphatic Amine, primary OR Aryl OR Pyrazole by Organic Functional groups ONLY

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Aliphatic Amine, primary OR Aryl OR Overlapping groups OR Pyrazole by Organic Functional groups (nested) ONLY

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as 1,1-Diaminoalkene derivative [C=C(N)N]  OR Aliphatic Carbon [CH] OR Aliphatic Carbon [-CH2-] OR Aliphatic Carbon [-CH3] OR Aliphatic Nitrogen, one aromatic attach [-N] OR Aromatic Carbon [C] OR Aromatic Nitrogen, five-member ring OR Azomethine, aliphatic attach [-N=C] OR Hydrazine [>N-N<] OR Nitrogen, two or tree olefinic attach [>N-] OR Olefinic carbon [=CH- or =C<] by Organic functional groups (US EPA) ONLY

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Aromatic compound OR CO2 derivative (general) OR Heterocyclic compound by Organic functional groups, Norbert Haider (checkmol) ONLY

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.3 ONLY

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as SN1 AND SN1 >> Nitrenium Ion formation AND SN1 >> Nitrenium Ion formation >> Primary (unsaturated) heterocyclic amine by DNA binding by OECD ONLY

Domain logical expression index: "g"

Similarity boundary:Target: CC1C=C(N)N(c2ccccc2)N=1
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "h"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.618

Domain logical expression index: "i"

Parametric boundary:The target chemical should have a value of log Kow which is <= 2.12

Conclusions:

5-Amino-3-methyl-1-phenyl-pyrazol 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.

Executive summary:

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 5-Amino-3-methyl-1-phenyl-pyrazol (IUPAC name: 3-methyl-1-phenylpyrazol-5-ylamine). 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. 5-Amino-3-methyl-1-phenyl-pyrazol 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:

Data available for the target chemical was reviewed to determine the mutagenic nature of 5-Amino-3-methyl-1-phenyl- pyrazol . The studies are 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 5-Amino-3-methyl-1-phenyl-pyrazol (IUPAC name: 3-methyl-1-phenylpyrazol-5-ylamine). 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. 5-Amino-3-methyl-1-phenyl-pyrazol 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 5-Amino-3-methyl-1-phenyl-pyrazol (CAS no 1131 -18 -6). The study was performed as per the standard plate protocol using Salmonella typhimurium strains TA98 and TA100 in the presence and absence of S9 metabolic activation system. The test chemical was dissolved in DMSO and used at dose levels of 0, 100, 500, 2500 or 5000 µg/plate. Concurrent solvent and positive controls chemicals were also included in the study. 2- aminoanthracene was used as the positive control chemical. 5-Amino-3-methyl-1-phenyl-pyrazol induced gene mutation in Salmonella typhimurium strains TA98 (weakly positive) and TA100 in the presence of S9 metabolic activation system. It however failed to induce gene mutation in the two strains in the absence of S9 metabolic activation system.

In a study by Zeiger et al (Environmental and molecular mutagenesis, 1992) for structurally and functionally simlar read across chemical, gene mutation toxicity study was performed to determine the mutagenic nature of 2-Aminobenzimidazole (RA CAS no 934 -37 -2; IUPAC name: 1H-bezimidazol-2 -amine). The study was performed using Salmonella typhimurium strainsTA97, TA98, TA100, TA1535 and TA1537 in the presence and absence of S9 metabolic activation system. The chemical was dissolved in DMSO as solvent and used at dose levels 0, 33, 100, 333, 1000, 3333, 6666 or 10000µg/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. 2-Aminobenzimidazole did not induce mutation in Salmonella typhimurium TA97, TA98, TA100, TA1535 and TA1537 in the presence and absence of S9 metabolic activation system and hence is not likely to classify as a gene mutant in vitro.

In another study for structurally and functionally similar read across chemical, gene mutation toxicity study was performed by Crocker et al (Mutation reaserch, 1992) to determine the mutagenic nature of Amitrole (RA CAS no 61 -82 -5; IUPAC name: 1H-1,2,4-triazol-3-amine). The study was performed using Salmonella typhimurium strains TA98 in the presence and absence of prostaglandin H synthase (PHS) metabolic activation system. The chemical was tested at dose levels0, 1.0, 3.16 or 10 mg/plate by the preincubation method. The revertants colonies on the plates were read after 72 hrs exposure duration. The ability of on the growth of his+ and his- cultures of TA98 were also checked. In addition to the mutagenicity assay, the influence of pH of the preincubation conditions on mutagenicity was also determined. Amitrole did not induce mutation in Salmonella typhimurium TA98 in the presence and absence of prostaglandin H synthase metabolic activation system and hence it is not likely to classify as a gene mutant in vitro. There was no evidence of interference with histidine biosynthesis or cell growth in either strain of bacteria. Amitrole was also non-mutagenic under the conditions of influence of pH on the preincubation condition of mutagenicity.

Based on the data available for the target chemical and its read across, 5-Amino-3-methyl-1-phenyl-pyrazol is not likely to classify as a gene mutant in vitro. Hence the test chemical cannot be classified as a gene mutant in vitro. One of the study mentioned for the target chemical indicating the positive gene mutation effect is from an old and non-standard study. The mentioned study uses only a few strains for the experiment and hence it is considered to be a K3 study. Considering this, testing is proposed for the chromosomal aberration study for the target chemical. Hence, the test chemical is considered to be negative for gene mutation in vitro.

Justification for classification or non-classification

Based on the data available for the target chemical and its read across, 5-Amino-3-methyl-1-phenyl-pyrazol is not likely to classify as a gene mutant in vitro. Hence the test chemical cannot be classified as a gene mutant in vitro. One of the study mentioned for the target chemical indicating the positive gene mutation effect is from an old and non-standard study. The mentioned study uses only a few strains for the experiment and hence it is considered to be a K3 study. Considering this, testing is proposed for the chromosomal aberration study for the target chemical. Hence, the test chemical is considered to be negative for gene mutation in vitro.