5-[[p-(benzylmethylamino)phenyl]azo]-1,4-dimethyl-1H-1,2,4-triazolium chloride

Endpoint summary

Description of key information

Skin sensitization :

The skin sensitization potential of 5-[[p-(benzylmethylamino)phenyl]azo]-1,4-dimethyl-1H-1,2,4-triazolium chloridewa s estimated using OECD QSAR toolbox v3.3 with logPow as the primary descriptor.

5-[[p-(benzylmethylamino)phenyl]azo]-1,4-dimethyl-1H-1,2,4-triazolium chloride was estimated to be not sensitizing to the skin of guinea pigs.

Based on the estimated results, 5-[[p-(benzylmethylamino)phenyl]azo]-1,4-dimethyl-1H-1,2,4-triazolium chloride can be considered to be not sensitizing to skin and can be classified under the category “Not Classified” as per CLP regulation.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Remarks:

in vivo

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 adequate and reliable documentation / justification

Justification for type of information:

Data is predicted using OECD QSAR toolbox version 3.3 and QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: estimated data

Principles of method if other than guideline:

Prediction was done by using OECD QSAR toolbox v3.3

GLP compliance:

not specified

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

Not specified

Specific details on test material used for the study:

- Name of the test material: 5-[[p-(benzylmethylamino)phenyl]azo]-1,4-dimethyl-1H-1,2,4-triazolium chloride
- IUPAC name: 5-[[p-(benzylmethylamino)phenyl]azo]-1,4-dimethyl-1H-1,2,4-triazolium chloride
- Molecular formula: C18H21N6Cl
- Moleclar weight: 356.8589 g/mol
- Substance type: Organic
- Smiles: Cc1cn[n+](n1/N=N/c2ccc(cc2)N(C)Cc3ccccc3)C.[Cl-]
- Inchi: 1S/C18H21N6.ClH/c1-15-13-19-23(3)24(15)21-20-17-9-11-18(12-10-17)22(2)14-16-7-5-4-6-8-16;/h4-13H,14H2,1-3H3;1H/q+1;/p-1/b21-20+;

Species:

guinea pig

Strain:

not specified

Sex:

not specified

Details on test animals and environmental conditions:

No data available

Route:

other: Not specified

Vehicle:

not specified

Concentration / amount:

No data available

Day(s)/duration:

No data available

Adequacy of induction:

not specified

No.:

#1

Route:

other: Not specified

Vehicle:

not specified

Concentration / amount:

No data available

Day(s)/duration:

No data available

Adequacy of challenge:

not specified

No. of animals per dose:

No data available

Details on study design:

No data available

Challenge controls:

No data available

Positive control substance(s):

not specified

Reading:

1st reading

Group:

test chemical

Dose level:

No data available

No. with + reactions:

0

Clinical observations:

No data available

Remarks on result:

no indication of skin sensitisation

Cellular proliferation data / Observations:

no indication of skin reaction estimated

The prediction was based on dataset comprised from the following descriptors: "Skin Sensitisation"
Estimation method: Takes highest mode value from the 11 nearest neighbours
Domain  logical expression:Result: In Domain

((((((((((((("a" or "b" )  and "c" )  and "d" )  and ("e" and ( not "f") )  )  and ("g" and ( not "h") )  )  and ("i" and ( not "j") )  )  and "k" )  and ("l" and ( not "m") )  )  and ("n" and ( not "o") )  )  and ("p" and ( not "q") )  )  and ("r" and ( not "s") )  )  and ("t" and ( not "u") )  )  and ("v" and "w" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Michael addition OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Arenes OR SN1 OR SN1 >> Iminium Ion Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines OR SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >> Aromatic azo OR SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine OR SN1 >> Nitrenium Ion formation >> Unsaturated heterocyclic azo by DNA binding by OECD ONLY

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Aliphatic Amines by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "c"

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: "d"

Referential boundary: The target chemical should be classified as Michael addition AND Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals AND Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Arenes AND SN1 AND SN1 >> Iminium Ion Formation AND SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines AND SN1 >> Nitrenium Ion formation AND SN1 >> Nitrenium Ion formation >> Aromatic azo AND SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine AND SN1 >> Nitrenium Ion formation >> Unsaturated heterocyclic azo by DNA binding by OECD ONLY

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as No alert found by Protein binding by OECD

Domain logical expression index: "f"

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 >> Acetates OR Acylation >> Direct Acylation Involving a Leaving group >> Azlactone OR Acylation >> Ring Opening Acylation OR Acylation >> Ring Opening Acylation >> alpha-Lactams OR Michael addition OR Michael addition >> Polarised Alkenes OR Michael addition >> Polarised Alkenes >> Polarised alkene - cyano OR Michael addition >> Polarised Alkenes >> Polarised alkene - esters OR SN2 OR SN2 >> SN2 reaction at a sulphur atom OR SN2 >> SN2 reaction at a sulphur atom >> Disulfides OR SN2 >> SN2 reaction at sp3 carbon atom OR SN2 >> SN2 reaction at sp3 carbon atom >> Alkyl diazo OR SN2 >> SN2 reaction at sp3 carbon atom >> Allyl acetates and related chemicals OR SN2 >> SN2 reaction at sp3 carbon atom >> alpha-Halobenzyls (and related cyano, sulfate and sulphonate subs. chem.) OR SN2 >> SN2 reaction at sp3 carbon atom >> alpha-Halocarbonyls by Protein binding by OECD

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Lipid Solubility < 0.01 g/kg AND (!Undefined)Group CN Lipid Solubility < 0.4 g/kg AND Group All Melting Point > 200 C AND Group CN Melting Point > 180 C AND Group CN Molecular Weight > 290 g/mol AND Group CN Vapour Pressure < 0.001 Pa by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as (!Undefined)Group All log Kow < -3.1 OR (!Undefined)Group All log Kow > 9 OR (!Undefined)Group All Melting Point > 200 C OR (!Undefined)Group C Surface Tension > 62 mN/m OR (!Undefined)Group CNHal Lipid Solubility < 4 g/kg OR (!Undefined)Group CNHal Lipid Solubility < 400 g/kg OR (!Undefined)Group CNS Surface Tension > 62 mN/m OR Group All log Kow < -3.1 OR Group All log Kow > 9 OR Group C Aqueous Solubility < 0.0001 g/L OR Group C Melting Point > 55 C OR Group C Molecular Weight > 350 g/mol OR Group C Vapour Pressure < 0.0001 Pa OR Group CN Aqueous Solubility < 0.0001 g/L OR Group CN Aqueous Solubility < 0.1 g/L OR Group CN log Kow > 4.5 OR Group CN log Kow > 5.5 OR Group CN Molecular Weight > 540 g/mol OR Group CNHal Aqueous Solubility < 0.001 g/L OR Group CNHal Aqueous Solubility < 0.1 g/L OR Group CNHal log Kow > 3.8 OR Group CNHal Molecular Weight > 370 g/mol OR Group CNHal Molecular Weight > 380 g/mol OR Group CNS log Kow < 0.5 OR Group CNS Melting Point > 120 C OR Group CNS Melting Point > 50 C OR Group CNS Molecular Weight > 620 g/mol by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Inclusion rules not met by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Alkylalkanol-amines OR Aromatic amines OR Ketones OR Phenols OR Quaternary organic ammonium compounds OR Tertiary aliphatic amine by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Halogens AND Non-Metals by Groups of elements

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Alkali Earth OR Metalloids OR Transition Metals by Groups of elements

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Group 14 - Carbon C AND Group 15 - Nitrogen N AND Group 17 - Halogens Cl AND Group 17 - Halogens F,Cl,Br,I,At by Chemical elements

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Group 16 - Oxygen O OR Group 16 - Sulfur S OR Group 17 - Halogens F by Chemical elements

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Amidine AND Ammonium salt AND Aromatic amine AND Aryl AND Azo AND Benzyl AND Unsaturated heterocyclic amine AND Unsaturated heterocyclic fragment by Organic Functional groups

Domain logical expression index: "q"

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

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as Amidine AND Ammonium salt AND Aromatic amine AND Aryl AND Azo AND Benzyl AND Unsaturated heterocyclic amine AND Unsaturated heterocyclic fragment by Organic Functional groups

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as Imidazole by Organic Functional groups

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as Amidine AND Ammonium salt AND Aromatic amine AND Aryl AND Azo AND Benzyl AND Unsaturated heterocyclic amine AND Unsaturated heterocyclic fragment by Organic Functional groups

Domain logical expression index: "u"

Referential boundary: The target chemical should be classified as Saturated heterocyclic amine by Organic Functional groups

Domain logical expression index: "v"

Parametric boundary:The target chemical should have a value of log Kow which is >= -2.18

Domain logical expression index: "w"

Parametric boundary:The target chemical should have a value of log Kow which is <= 4.47

Interpretation of results:

other: Not sensitizing

Executive summary:

The skin sensitization potential of 5-[[p-(benzylmethylamino)phenyl]azo]-1,4-dimethyl-1H-1,2,4-triazolium chloridewa s estimated using OECD QSAR toolbox v3.3 with logPow as the primary descriptor.

5-[[p-(benzylmethylamino)phenyl]azo]-1,4-dimethyl-1H-1,2,4-triazolium chloride was estimated to be not sensitizing to the skin of guinea pigs.

Based on the estimated results, 5-[[p-(benzylmethylamino)phenyl]azo]-1,4-dimethyl-1H-1,2,4-triazolium chloride can be considered to be not sensitizing to skin and can be classified under the category “Not Classified” as per CLP regulation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Skin sensitization:

In different studies, 5-[[p-(benzylmethylamino)phenyl]azo]-1,4-dimethyl-1H-1,2,4-triazolium chloride has been investigated for potential for dermal irritation to a greater or lesser extent. The studies are based on in vivo experiments in rabbits along with human data for target chemical and its structurally similar read across substance 2-[[4-(Di-methyl amino)phenyl] azo]-1,3-dimethyl-1H-imidazolium chloride (77061-58-6) and closely related read across substance 2,2',2'',2'''-(ethane-1,2-diyldinitrilo)tetra aceto nitrile (5766-67-6) . The predicted data using the OECD QSAR toolbox has also been compared with the experimental data.

The skin sensitization potential of 5-[[p-(benzylmethylamino)phenyl]azo]-1,4-dimethyl-1H-1,2,4-triazolium chloridewa s estimated using OECD QSAR toolbox v3.3 with logPow as the primary descriptor.

5-[[p-(benzylmethylamino)phenyl]azo]-1,4-dimethyl-1H-1,2,4-triazolium chloride was estimated to be not sensitizing to the skin of guinea pigs.

Based on the estimated results, 5-[[p-(benzylmethylamino)phenyl]azo]-1,4-dimethyl-1H-1,2,4-triazolium chloride can be considered to be not sensitizing to skin and can be classified under the category “Not Classified” as per CLP regulation.

The above estimated result is supported by experimental data summarized in Opinion of the SCCNFP on Basic red 51 during the 25th plenary meeting 2003 for the 2-[[4-(Di-methyl amino)phenyl] azo]-1,3-dimethyl-1H-imidazolium chloride (77061-58-6).

2-[[4-(Di-methyl amino)phenyl] azo]-1,3-dimethyl-1H-imidazolium chloride was used as a test material to evaluated its skin sensitization potential by Magnusson and Kligman Guinea pig maximisation test The test was performed according to OECD guideline 406.

 

 The test material was subjected to the guinea pig by intadermal and topical induction . In intradermal induction 5% aqueous solution with and without Freund’s Complete Adjuvant was subjected to test animal whereas, in topical induction ,50% preparation of test material underocclusion for 48 hours. Controls received vehicle only.

After 14 days of induction challenge dode was introduced on the guinea pigs by exposing 25% aqueous dilution of the test substance for 24 hours under occlusion. Animals were observed after 24 and 48 hrs

None of the animals of the control or test group were observed with skin reactions after challenge with a non-irritating preparation of 25% of the test material . Hence,2-[[4-(Di-methyl amino)phenyl] azo]-1,3-dimethyl-1H-imidazolium chloride was considered to be not sensitizing to guinea pig skin.

The above experimental result was supported by experimental study summarized in Robust Summaries & Test Plans of 2,2',2'',2'''-(ethane-1,2-diyldinitrilo)tetra aceto nitrile , US Environmental Protection Agency 2002 for the closely related read across substance 2,2',2'',2'''-(ethane-1,2-diyldinitrilo)tetra aceto nitrile (5766-67-6).

2,2',2'',2'''-(ethane-1,2-diyldinitrilo)tetra aceto nitrile was used as test material to evaluate its skin sensitization potential. The study was conducted as per OECD 406 ( skin sensitization)

2,2',2'',2'''-(ethane-1,2-diyldinitrilo)tetra aceto nitrile was applied dermally on the skin of Dunkin Hartley Guinea Pig in the concentration 0.1 in day 1 and 50% on day 8 of induction.

On day 21 challenge treatment was subjected dermally with the concentration 50% for 24 hrs.There was no irritation seen 24 or 48 hours after challenge applicationHence,2,2',2'',2'''-(ethane-1,2-diyldinitrilo)tetra aceto nitrile was not considered to be skin sensitizing. 

 Based on the available data for the target and read across substances and applying the weight of evidence approach, 5-[[p-(benzylmethylamino)phenyl]azo]-1,4-dimethyl-1H-1,2,4-triazolium chloride can be considered to be not sensitizing to skin.Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified.”

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

 Based on the available data for the target and read across substances and applying the weight of evidence approach, 5-[[p-(benzylmethylamino)phenyl]azo]-1,4-dimethyl-1H-1,2,4-triazolium chloride can be considered to be not sensitizing to skin.Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified.”