Registration Dossier

Skin Irritation:

The dermal irritation potential of 1,4-dimethyl-5-[[4-[methylbenzylamino]phenyl]azo]-1H-1,2,4-triazolium acetate was estimated using OECD QSAR toolbox v3.3 with logPow as the primary descriptor.

1,4-dimethyl-5-[[4-[methylbenzylamino]phenyl]azo]-1H-1,2,4-triazolium acetate was estimated to be not irritating to the skin of New Zealand White rabbits.

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

Eye Irritation:

The ocular irritation potential of 1,4-dimethyl-5-[[4-[methylbenzylamino]phenyl]azo]-1H-1,2,4-triazolium acetate was estimated using OECD QSAR toolbox v3.3 with logPow as the primary descriptor.

1,4-dimethyl-5-[[4-[methylbenzylamino]phenyl]azo]-1H-1,2,4-triazolium acetate was estimated to be not irritating to the eyes of New Zealand White rabbits.

Based on the estimated results, Isoamyl Phenylacetate can be considered to be not irritating to eyes and can be classified under the category “Not Classified” as per CLP regulation.

Reference

Endpoint:

skin irritation: 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 limited documentation / justification

Justification for type of information:

data is from OECD QSAR v3.3 and the QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: Estimated data

Principles of method if other than guideline:

Prediction was done using OECD QSAR toolbox v3.3

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material: 1,4-dimethyl-5-[[4-[methylbenzylamino]phenyl]azo]-1H-1,2,4-triazolium acetate
- IUPAC name: 1,4-dimethyl-5-[[4-[methylbenzylamino]phenyl]azo]-1H-1,2,4-triazolium acetate
- Molecular formula: C18H21N6.C2H3O2
- Molecular weight: 380.4496 g/mole
- Smiles : CC(=O)[O-].Cn1cn[n+](c1/N=N/c2ccc(cc2)N(C)Cc3ccccc3)C
- Inchl: 1S/C18H21N6.C2H4O2/c1-22(13-15-7-5-4-6-8-15)17-11-9-16(10-12-17)20-21-18-23(2)14-19-24(18)3;1-2(3)4/h4-12,14H,13H2,1-3H3;1H3,(H,3,4)/q+1;/p-1
- Substance type: Organic
- Physical state: liquid

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

no data available

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

not specified

Controls:

not specified

Amount / concentration applied:

500 mg

Duration of treatment / exposure:

4 hours

Observation period:

72 hours

Number of animals:

3

Details on study design:

no data available

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

72 h

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

No signs of irritation observed

Estimation method: Takes mode value from the 5 nearest neighbours
Domain logical expression:Result: In Domain

((((((((((((((("a" or "b" ) and "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 ( not "q") ) ) and ("r" and ( not "s") ) ) and ("t" and ( not "u") ) ) and ("v" and ( not "w") ) ) and ("x" and ( not "y") ) ) and ("z" and ( not "aa") ) ) and ("ab" and "ac" ) )

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 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: "d"

Referential boundary: The target chemical should be classified as Non binder, without OH or NH2 group by Estrogen Receptor Binding

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Non binder, impaired OH or NH2 group OR Non binder, MW>500 OR Non binder, non cyclic structure OR Strong binder, OH group OR Very strong binder, OH 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 >> Carbamates OR Acylation >> Ester aminolysis OR Acylation >> Ester aminolysis >> Amides OR Acylation >> Ester aminolysis >> Dithiocarbamates OR Nucleophilic addition OR Nucleophilic addition >> Addition to carbon-hetero double bonds OR Nucleophilic addition >> Addition to carbon-hetero double bonds >> Ketones OR Radical reactions OR Radical reactions >> Free radical formation OR Radical reactions >> Free radical formation >> Hydroperoxides OR Radical reactions >> Free radical formation >> Organic peroxy compounds OR SN2 OR SN2 >> Nucleophilic substitution at sp3 carbon atom OR SN2 >> Nucleophilic substitution at sp3 carbon atom >> Alkyl halides OR SN2 >> Nucleophilic substitution at sp3 carbon atom >> Sulfonates OR SN2 >> Nucleophilic substitution on benzilyc carbon atom OR SN2 >> Nucleophilic substitution on benzilyc carbon atom >> alpha-Activated benzyls 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 (!Undefined)Group All Lipid Solubility < 0.01 g/kg AND (!Undefined)Group C Surface Tension > 62 mN/m AND (!Undefined)Group CN Lipid Solubility < 0.4 g/kg AND Group All Melting Point > 200 C AND Group C Melting Point > 55 C AND Group C Molecular Weight > 350 g/mol AND Group C Vapour Pressure < 0.0001 Pa 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: "i"

Referential boundary: The target chemical should be classified as (!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 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 CNS Melting Point > 120 C OR Group CNS Melting Point > 50 C by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "j"

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: "k"

Referential boundary: The target chemical should be classified as Esters including acrylic and methacrylic esters OR Ketones OR Quaternary organic ammonium compounds by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Not categorized by Repeated dose (HESS)

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as 3-Methylcholantrene (Hepatotoxicity) Alert OR Aliphatic amines (Mucous membrane irritation) Rank C OR Amineptine (Hepatotoxicity) Alert OR Anilines (Hemolytic anemia with methemoglobinemia) Rank A OR Anilines (Hepatotoxicity) Rank C OR Aromatic hydrocarbons (Liver enzyme induction) Rank C OR Chlorphentermine (Hepatotoxicity) Alert OR Tamoxifen (Hepatotoxicity) Alert OR Thiocarbamates/Sulfides (Hepatotoxicity) No rank by Repeated dose (HESS)

Domain logical expression index: "n"

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

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Aliphatic Amine, tertiary OR Alkane, branched with tertiary carbon OR Alkene OR Alkoxy OR AlkoxySilane OR Alkyl arenes OR Alkyl halide OR Allyl by Organic Functional groups

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Acetoxy AND Amidine AND Ammonium salt AND Aromatic amine AND Aryl AND Azo AND Benzyl AND Carboxylic acid 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 OR Aliphatic Amine, secondary by Organic Functional groups

Domain logical expression index: "r"

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

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as Carboxamide OR Cycloalkane OR Dihydropurinedione OR Dihydroxyl group OR Ether OR Formylamino by Organic Functional groups (nested)

Domain logical expression index: "t"

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

Domain logical expression index: "u"

Referential boundary: The target chemical should be classified as Fused saturated heterocycles by Organic Functional groups (nested)

Domain logical expression index: "v"

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

Domain logical expression index: "w"

Referential boundary: The target chemical should be classified as Guanidine OR Hydantoin OR Imidazolidine by Organic Functional groups (nested)

Domain logical expression index: "x"

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

Domain logical expression index: "y"

Referential boundary: The target chemical should be classified as Morpholine by Organic Functional groups (nested)

Domain logical expression index: "z"

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

Domain logical expression index: "aa"

Referential boundary: The target chemical should be classified as Lactams by Organic Functional groups (nested)

Domain logical expression index: "ab"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.0685

Domain logical expression index: "ac"

Parametric boundary:The target chemical should have a value of log Kow which is <= 1.57

Interpretation of results:

other: not irritating

Conclusions:

1,4-dimethyl-5-[[4-[methylbenzylamino]phenyl]azo]-1H-1,2,4-triazolium acetate was estimated to be not irritating to the skin of New Zealand White rabbits.

Executive summary:

The dermal irritation potential of 1,4-dimethyl-5-[[4-[methylbenzylamino]phenyl]azo]-1H-1,2,4-triazolium acetate was estimated using OECD QSAR toolbox v3.3 with logPow as the primary descriptor.

1,4-dimethyl-5-[[4-[methylbenzylamino]phenyl]azo]-1H-1,2,4-triazolium acetate was estimated to be not irritating to the skin of New Zealand White rabbits.

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

Endpoint conclusion:

no adverse effect observed (not irritating)

Reference

Endpoint:

eye irritation: 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 limited documentation / justification

Justification for type of information:

data is from OECD QSAR toolbox v 3.3 and tje QMRF report hase been attached

Qualifier:

according to guideline

Guideline:

other: Estimated data

Principles of method if other than guideline:

Prediction was done using OECD QSAR toolbox v3.3

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material: 1,4-dimethyl-5-[[4-[methylbenzylamino]phenyl]azo]-1H-1,2,4-triazolium acetate
- IUPAC name: 1,4-dimethyl-5-[[4-[methylbenzylamino]phenyl]azo]-1H-1,2,4-triazolium acetate
- Molecular formula: C18H21N6.C2H3O2
- Molecular weight: 380.4496 g/mole
- Smiles : CC(=O)[O-].Cn1cn[n+](c1/N=N/c2ccc(cc2)N(C)Cc3ccccc3)C
- Inchl: 1S/C18H21N6.C2H4O2/c1-22(13-15-7-5-4-6-8-15)17-11-9-16(10-12-17)20-21-18-23(2)14-19-24(18)3;1-2(3)4/h4-12,14H,13H2,1-3H3;1H3,(H,3,4)/q+1;/p-1
- Substance type: Organic
- Physical state: liquid

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

no data available

Vehicle:

not specified

Controls:

not specified

Amount / concentration applied:

0.1ml

Duration of treatment / exposure:

single exposure

Observation period (in vivo):

21 days

Duration of post- treatment incubation (in vitro):

no data available

Number of animals or in vitro replicates:

no data available

Details on study design:

no data available

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

21 d

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

No signs of irritation observed

Estimation method: Takes mode value from the 8 nearest neighbours
Domain logical expression:Result: In Domain

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

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 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: "d"

Referential boundary: The target chemical should be classified as Non binder, without OH or NH2 group by Estrogen Receptor Binding

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Non binder, impaired OH or NH2 group OR Non binder, MW>500 OR Non binder, non cyclic structure OR Strong binder, OH group OR Very strong binder, OH group OR Weak binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "f"

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

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Not categorized by Repeated dose (HESS)

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as 3-Methylcholantrene (Hepatotoxicity) Alert OR Aliphatic amines (Mucous membrane irritation) Rank C OR Allyl esters (Hepatotoxicity) Rank A OR Amineptine (Hepatotoxicity) Alert OR Anilines (Hemolytic anemia with methemoglobinemia) Rank A OR Anilines (Hepatotoxicity) Rank C OR Aromatic hydrocarbons (Liver enzyme induction) Rank C OR Chlorphentermine (Hepatotoxicity) Alert OR Tamoxifen (Hepatotoxicity) Alert OR Thiocarbamates/Sulfides (Hepatotoxicity) No rank by Repeated dose (HESS)

Domain logical expression index: "i"

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

Domain logical expression index: "j"

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 >> Carbamates OR Acylation >> Ester aminolysis OR Acylation >> Ester aminolysis >> Amides OR Acylation >> Ester aminolysis >> Dithiocarbamates OR Nucleophilic addition OR Nucleophilic addition >> Addition to carbon-hetero double bonds OR Nucleophilic addition >> Addition to carbon-hetero double bonds >> Ketones OR Radical reactions OR Radical reactions >> Free radical formation OR Radical reactions >> Free radical formation >> Hydroperoxides OR SN2 OR SN2 >> Nucleophilic substitution on benzilyc carbon atom OR SN2 >> Nucleophilic substitution on benzilyc carbon atom >> alpha-Activated benzyls 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 alerts for skin sensitization by OASIS v1.3

Domain logical expression index: "k"

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

Domain logical expression index: "l"

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

Domain logical expression index: "m"

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

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Aliphatic N-nitro group OR alpha,beta-unsaturated carbonyls OR Hydrazine OR N-methylol derivatives OR No alert found OR Polycyclic Aromatic Hydrocarbons by in vivo mutagenicity (Micronucleus) alerts by ISS

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Not known precedent reproductive and developmental toxic potential by DART scheme v.1.0

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as ARA inhibitors, Candesartan-like chemicals (5c-3) OR ARA inhibitors, Candesartan-like chemicals (5c-3) >> Candesartan-like ARA inhibitors OR Barbital and ETU, PLTU-like derivatives (17a) OR Known precedent reproductive and developmental toxic potential OR Purine and pyrimidine-like derivatives (7b) OR Toluene and small alkyl toluene derivatives (8a) by DART scheme v.1.0

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Aromatic-CH2 AND Aromatic-H AND Azo group   [-N=N-] AND Benzene AND -CH - [cyclic] AND Methyl [-CH3] AND Quaternary amine AND Tertiary amine AND Unsubstituted phenyl group (C6H5-) by Bioaccumulation - metabolism alerts

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as -C=CH [alkenyl hydrogen] by Bioaccumulation - metabolism alerts

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as Aromatic-CH2 AND Aromatic-H AND Azo group   [-N=N-] AND Benzene AND -CH - [cyclic] AND Methyl [-CH3] AND Quaternary amine AND Tertiary amine AND Unsubstituted phenyl group (C6H5-) by Bioaccumulation - metabolism alerts

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as Carbon with 4 single bonds & no hydrogens by Bioaccumulation - metabolism alerts

Domain logical expression index: "u"

Referential boundary: The target chemical should be classified as Aromatic-CH2 AND Aromatic-H AND Azo group   [-N=N-] AND Benzene AND -CH - [cyclic] AND Methyl [-CH3] AND Quaternary amine AND Tertiary amine AND Unsubstituted phenyl group (C6H5-) by Bioaccumulation - metabolism alerts

Domain logical expression index: "v"

Referential boundary: The target chemical should be classified as Ester   [-C(=O)-O-C] by Bioaccumulation - metabolism alerts

Domain logical expression index: "w"

Referential boundary: The target chemical should be classified as Aromatic-CH2 AND Aromatic-H AND Azo group   [-N=N-] AND Benzene AND -CH - [cyclic] AND Methyl [-CH3] AND Quaternary amine AND Tertiary amine AND Unsubstituted phenyl group (C6H5-) by Bioaccumulation - metabolism alerts

Domain logical expression index: "x"

Referential boundary: The target chemical should be classified as -CH2- [linear] by Bioaccumulation - metabolism alerts

Domain logical expression index: "y"

Parametric boundary:The target chemical should have a value of log Kow which is >= -0.874

Domain logical expression index: "z"

Parametric boundary:The target chemical should have a value of log Kow which is <= 3.17

Interpretation of results:

other: not irritating

Conclusions:

1,4-dimethyl-5-[[4-[methylbenzylamino]phenyl]azo]-1H-1,2,4-triazolium acetate was estimated to be not irritating to the eyes of New Zealand White rabbits.

Executive summary:

The ocular irritation potential of 1,4-dimethyl-5-[[4-[methylbenzylamino]phenyl]azo]-1H-1,2,4-triazolium acetate was estimated using OECD QSAR toolbox v3.3 with logPow as the primary descriptor.

1,4-dimethyl-5-[[4-[methylbenzylamino]phenyl]azo]-1H-1,2,4-triazolium acetate was estimated to be not irritating to the eyes of New Zealand White rabbits.

Based on the estimated results, Isoamyl Phenylacetate can be considered to be not irritating to eyes and can be classified under the category “Not Classified” as per CLP regulation.

Endpoint conclusion:

no adverse effect observed (not irritating)

Endpoint conclusion:

no study available

Skin Irritation:

Several studies have been investigated to assess the dermal irritation potential of 1,4-dimethyl-5-[[4-[methylbenzylamino]phenyl]azo]-1H-1,2,4-triazolium acetate. These studies include in vivo as well as predicted results for the target and its closely related substances, 2-[[4-(Di-methyl amino)phenyl] azo]-1,3-dimethyl-1H-imidazolium chloride[CAS: 77061 -58-6] and 1,3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione[CAS: 58-08-2].The predicted data using the OECD QSAR toolbox has also been compared with the experimental data.

In a prediction done by SSS (2017) using the OECD QSAR toolbox v3.3 with log kow as the primary descriptor, the dermal irritation potential was estimated for1,4-dimethyl-5-[[4 -[methylbenzylamino]phenyl]azo]-1H-1,2,4-triazolium acetate. 1,4-dimethyl-5-[[4-[methylbenzylamino]phenyl]azo]-1H-1,2,4-triazolium acetate was estimated to be not irritating to the skin of New Zealand White rabbits.

This is supported by the experimental study summarized in Opinion of the SCCNFP on Basic red 51 during the 25th plenary meeting 2003; for the closely related substance, 2-[[4 -(Di-methyl amino)phenyl] azo]-1,3-dimethyl-1H-imidazolium chloride[CAS: 77061-58-6]. 50 % (w/w) aqueous solution was applied on the skin of 2 male and 1 female Vienna White rabbits in semi-occlusive conditions for 4 hrs. The application patches were removed, and the application sites were washed with water and Lutrol/water (1/1). The skin was scored at 30-60 minutes after removal of the patches and at 24, 48, and 72 h.

The above studies are also supported by the result summarized in Hazardous Substances Data Bank (HSDB) For the CAS: 58-08-2, U.S National Library of Medicine, last updated 2014; for the closely related read across substance, 1,3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione[CAS:58-08-2].The study was performed as per OECD 404 Guidelines.

50 % (w/w) aqueous solution was applied on the skin of 2 male and 1 female Vienna White rabbits in semi-occlusive conditions for 4 hrs. The application patches were removed, and the application sites were washed with water and Lutrol/water (1/1). The skin was scored at 30-60 minutes after removal of the patches and at 24, 48, and 72 h.

No signs of irritation were observed. The overall irritation index for each animal after 72hours was 0. Hence, 1,3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione[caffeine] was considered to be not irritating to skin.

Based on the available data for the target as well as read across substances and applying the weight of evidence approach,1,4-dimethyl-5-[[4-[methylbenzylamino]phenyl]azo]-1H-1,2,4-triazolium acetate. was not irritating to skin.Comparing the above annotations with the criteria of CLP regulation, test chemical can be classified under the category “Not Classified.”

Eye Irritation:

Several studies have been investigated to assess the ocular irritation potential of 1,4-dimethyl-5-[[4-[methylbenzylamino]phenyl]azo]-1H-1,2,4-triazolium acetate. These studies include in vivo as well as predicted results for the target and its closely related substances, Benzyldimethylamine [CAS: 103-83-3] and 1,3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6 -dione[CAS: 58-08-2].The predicted data using the OECD QSAR toolbox has also been compared with the experimental data.

In a prediction done by SSS (2017) using the OECD QSAR toolbox v3.3 with log kow as the primary descriptor, the ocular irritation potential was estimated for1,4-dimethyl-5-[[4 -[methylbenzylamino]phenyl]azo]-1H-1,2,4-triazolium acetate. 1,4-dimethyl-5-[[4-[methylbenzylamino]phenyl]azo]-1H-1,2,4-triazolium acetate was estimated to be not irritating to the eyes of New Zealand White rabbits.

This result is supported by the experimental study summarized in GESTIS - Substance Database (Information system on hazardous substances of the Berufsgenossenschaften), 2017 for the closely related substance,Benzyldimethylamine [CAS: 103-83-3]. Five μl of the test chemical was instilled in the conjunctival sac of the rabbits (number not mentioned) for 24 hours. The animals were observed for signs of irritation till 7 days.

Inflammation of the conjunctiva and the iris in rabbit eyes after an exposure period of 24 hours, accompanied by a severe damage of large areas of the cornea was observed in the test animals. These effects were completely reversible in 7 days.

Since the effects were fully reversible, benzyldimethylamine can be considered to be not irritating to eyes.

These results are further supported by the experimental study summarized in Hazardous Substances Data Bank (HSDB) For the CAS: 58-08-2, U.S National Library of Medicine, last updated 2014; for the closely related read across substance, 1,3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione[CAS:58-08-2]. The study was performed according to OECD 405 Guidelines. 0.1 ml (bulk volume; ca. 56 mg) undiluted test chemical was instilled into the right conjunctival sac of2 male and 1 female Vienna White rabbits. The treated eyes remained unwashed throughout the study. The eyes were scored at 1, 24, 48, and 72 hours and at 8 days post-instillation. Slight corneal opacity was observed in all 3 rabbits at 24h and in 1 rabbit at day 8. Slight to well-defined conjunctival redness was present in all 3 rabbits at 24h (grad 2) and in 1 rabbit at day 8; slight to moderate conjunctival swelling was observed in 1 rabbits at up to 48 hours. No iritis was observed.

The mean irritation scores were 0.9 (corneal opacity), 0.0 (iritis), 1.6 (conjunctival erythema), and 0.6 (conjunctival edema).

Based on the observations and scores, Caffeine was considered to be not irritating to rabbit eyes.

Based on the available data for the target as well as read across substances and applying the weight of evidence approach,1,4-dimethyl-5-[[4-[methylbenzylamino]phenyl]azo]-1H-1,2,4-triazolium acetate. was not irritating to eyes.Comparing the above annotations with the criteria of CLP regulation, test chemical can be classified under the category “Not Classified.”

Available data for 1,4-dimethyl-5-[[4-[methylbenzylamino]phenyl]azo]-1H-1,2,4-triazolium acetate indicates that it is not likely to cause any irritation to skin and eyes.

Hence, 1,4-dimethyl-5-[[4-[methylbenzylamino]phenyl]azo]-1H-1,2,4-triazolium acetate can be classified under the category “Not Classified” as per CLP regulation.