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Administrative data

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-methoxy-5-nitroanilinium chloride. 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-methoxy-5-nitroanilinium chloride 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, 2018
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-methoxy-5-nitroanilinium chloride
- IUPAC name: 2-methoxy-5-nitroanilinium chloride
- Molecular formula: C7H9ClN2O3
- Molecular weight: 204.6121g/mol
- Smiles: Cl.COc1ccc(cc1N)[N+](=O)[O-]
- Inchl: 1S/C7H8N2O3.ClH/c1-12-7-3-2-5(9(10)11)4-6(7)8;/h2-4H,8H2,1H3;1H
- 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 is done considering a dose dependent increase in the number if revertants/plate
Statistics:
No data
Species / strain:
S. typhimurium, other: TA 1535, TA 1537, TA 98, TA 100 and TA 102
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
Additional information on results:
No data
Remarks on result:
no mutagenic potential (based on QSAR/QSPR prediction)

The prediction was based on dataset comprised from the following descriptors: "Gene mutation"
Estimation method: Takes highest mode value from the 10 nearest neighbours
Domain  logical expression:Result: In Domain

(((((((("a" or "b" or "c" )  and ("d" and ( not "e") )  )  and ("f" and ( not "g") )  )  and ("h" and ( not "i") )  )  and ("j" and ( not "k") )  )  and ("l" and ( not "m") )  )  and ("n" and ( not "o") )  )  and ("p" and "q" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Radical AND Radical >> Radical mechanism via ROS formation (indirect) AND Radical >> Radical mechanism via ROS formation (indirect) >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids AND SN1 AND SN1 >> Nucleophilic attack after reduction and nitrenium ion formation AND SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids by DNA binding by OASIS v.1.3

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as SN1 AND SN1 >> Nitrenium Ion formation AND SN1 >> Nitrenium Ion formation >> Aromatic nitro by DNA binding by OECD

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Strong binder, NH2 group by Estrogen Receptor Binding

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Strong binder, NH2 group by Estrogen Receptor Binding

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Moderate binder, NH2 group OR Moderate binder, OH grooup OR Non binder, impaired OH or NH2 group OR Non binder, MW>500 OR Non binder, non cyclic structure OR Non binder, without OH or NH2 group OR Strong binder, OH group OR Very strong binder, OH group OR Weak binder, NH2 group OR Weak binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as No alert found by Protein binding by OASIS v1.3

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Direct acylation involving a leaving group OR Acylation >> Direct acylation involving a leaving group >> N-Acylsulfonamides  OR Acylation >> Ester aminolysis OR Acylation >> Ester aminolysis >> Amides OR Michael Addition OR Michael Addition >> Michael addition on conjugated systems with electron withdrawing group OR Michael Addition >> Michael addition on conjugated systems with electron withdrawing group >> Activated electrophilic ethenylarenes  OR Michael Addition >> Quinoide type compounds OR Michael Addition >> Quinoide type compounds >> Quinone methide(s)/imines; Quinoide oxime structure; Nitroquinones, Naphthoquinone(s)/imines  OR Nucleophilic addition OR Nucleophilic addition >> Nucleophilic addition reaction at polarized N-functional double bond OR Nucleophilic addition >> Nucleophilic addition reaction at polarized N-functional double bond >> C-Nitroso compounds  OR SN2 OR SN2 >> Nucleophilic substitution at sp3 carbon atom OR SN2 >> Nucleophilic substitution at sp3 carbon atom >> (Thio)Phosphates  OR SN2 >> SN2 Reaction at a sp3 carbon atom OR SN2 >> SN2 Reaction at a sp3 carbon atom >> Activated alkyl esters and thioesters  by Protein binding by OASIS v1.3

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as H-acceptor-path3-H-acceptor AND Nitro-aromatic by in vivo mutagenicity (Micronucleus) alerts by ISS

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as 1-phenoxy-benzene OR Aromatic diazo OR Aromatic mono- and dialkylamine OR Heterocyclic Polycyclic Aromatic Hydrocarbons OR Hydrazine OR No alert found OR Polycyclic Aromatic Hydrocarbons OR Primary aromatic amine, hydroxyl amine and its derived esters OR Quinones by in vivo mutagenicity (Micronucleus) alerts by ISS

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Aromatic Amine Type Compounds by Oncologic Primary Classification

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Halogenated Aromatic Hydrocarbon Type Compounds OR Not classified OR Phenol Type Compounds by Oncologic Primary Classification

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Aliphatic Amine, primary AND Ammonium salt AND Aryl AND Ether AND Nitrobenzene by Organic Functional groups

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Aliphatic Amine, secondary by Organic Functional groups

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Anilines (Hemolytic anemia with methemoglobinemia) Rank A AND Anilines (Hepatotoxicity) Rank C by Repeated dose (HESS)

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Nitrobenzenes (Hemolytic anemia with methemoglobinemia) Rank A OR Nitrobenzenes (Hepatotoxicity) Rank C OR Not categorized by Repeated dose (HESS)

Domain logical expression index: "p"

Parametric boundary:The target chemical should have a value of log Kow which is >= -5.34

Domain logical expression index: "q"

Parametric boundary:The target chemical should have a value of log Kow which is <= -0.906

Conclusions:
2-methoxy-5-nitroanilinium chloride 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 2-methoxy-5-nitroanilinium chloride. 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-methoxy-5-nitroanilinium chloride 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-methoxy-5- nitroanilinium chloride. The studies are as summarized 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-methoxy-5-nitroanilinium chloride. 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-methoxy-5-nitroanilinium chloride 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.

The predicted data is further supported by data from read across chemical.

The 50 -60% structurally similar read across chemical 2-nitro-4-aminophenol (RA CAS no 119 -34 -6; IUPAC name: 4-Amino-2-nitrophenol) was studied by Majdi Shahin ( International Journal of Cosmetic Science, 1985) to for its ability to induce mutations in strains of Salmonella typhimurium. Mutagenicity toxicity testing was performed to determine the mutagenic nature of 2-nitro-4-aminophenol. The study was performed using Salmonella typhimurium strains TA1535, TA100, TA1537, TA1538 and TA98 in the presence and absence of S9 metabolic activation system. The test chemical was dissolved in DMSO and used at dose levels of 0, 5, 10, 20, 50, 100, 250, 500 or 1000 µg/plate. Plates were incubated for three days at 37°C before counting the revertant colonies. Concurrent solvent and negative control chemicals were also included in the study. A dose-dependent two-fold increase in numbers of revertants per plate was used as the criterion for genetic activity of the compounds tested. A 2.5-fold increase over the spontaneous level, even without clear evidence of dose-dependence, was also considered to be an indication of genetic activity if found in repeated experiments. 2-nitro-4-aminophenol did not induce gene mutation in Salmonella typhimurium TA1535, TA100, TA1537, TA1538 and TA98 in the presence and absence of S9 metabolic activation system and hence it is not likely to classify as a gene mutant.

Gene mutation toxicity study was performed by Shimizu and Yano (Mutation Research, 1986) to determine the mutagenic nature of another 50 -60% structurally similar read across chemical m-Nitroacetophenone (RA CAS no 121 -89 -1; IUPAC name: ). The study was performed using Salmonella typhimurium strains TA98, TA100, TA1535, TA1538 and TA1537 in the presence and absence of S9 metabolic activation system using the preincubation protocol. The chemical was dissolved in DMSO as solvent and used at dose levels 0, 0.1, 0.5, 1, 5 or 10 mg/plate by the preincubation for 15 mins. The plates were incubated for 70 hrs in dark and observed for the presence of colonies. Concurrent solvent and positive control chemicals were also included in the study. m-Nitroacetophenonedid not induce mutation in Salmonella typhimurium strains TA98, TA100, TA1535, TA1538 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.

Based on the data available for the target chemical and its read across, 2-methoxy-5-nitroanilinium chloride 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-methoxy-5-nitroanilinium chloride (CAS no 67827 -72 -9) does not exhibit gene mutation in vitro. Hence the test chemical is not likely to classify as a gene mutant in vitro.