Registration Dossier

Skin Irritation:

The dermal irritation potential of 4-(phenylazo)benzene-1,3-diamine acetate was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor.

4-(phenylazo)benzene-1,3-diamine acetate was estimated to be corrosive to the skin of New Zealand White rabbits.

Based on the estimated result; 4-(phenylazo)benzene-1,3-diamine acetate can be considered corrosive to skin and can be classified under the category “Category 1” as per CLP regulation.

Eye Irritation:

The ocular irritation potential of 4-(phenylazo)benzene-1,3-diamine acetate was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor.

4-(phenylazo)benzene-1,3-diamine acetate was estimated to be corrosive to the eyes of New Zealand White rabbits.

Based on the estimated result; 4-(phenylazo)benzene-1,3-diamine acetate can be considered corrosive to the eyes and can be classified under the category “Category 1” 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 toolbox 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: 4-(phenylazo)benzene-1,3-diamine acetate
- IUPAC name: 4-(phenylazo)benzene-1,3-diamine acetate
- Molecular formula: C14H16N4O2
- Molecular weight: 272.306 g/mole
- Smiles Notation: c1(ccc(c(N)c1)\N=N\c1ccccc1)N.C(C)(=O)O
- InChl: 1S/C12H12N4.C2H4O2/c13-9-6-7-12(11(14)8-9)16-15-10-4-2-1-3-5-10;1-2(3)4/h1-8H,13-14H2;1H3,(H,3,4)/b16-15+;
- Substance type: Organic
- Physical state: Solid

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:

clipped

Vehicle:

not specified

Controls:

not specified

Amount / concentration applied:

0.5 ml

Duration of treatment / exposure:

4 hours

Observation period:

72 hours

Number of animals:

6

Details on study design:

no data available

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

72 h

Reversibility:

not specified

Remarks on result:

positive indication of irritation

Irritant / corrosive response data:

signs of irritation observed

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

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

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Anilines (Acute toxicity) AND Not categorized by US-EPA New Chemical Categories

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 azo AND SN1 >> Nitrenium Ion formation >> Primary aromatic amine 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 Anilines (amino-meta) AND Anilines (Unhindered) by Aquatic toxicity classification by ECOSAR

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

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Michael-type addition, quinoid structures OR AN2 >> Michael-type addition, quinoid structures >> Quinones OR AN2 >> Shiff base formation after aldehyde release OR AN2 >> Shiff base formation after aldehyde release >> Specific Acetate Esters OR Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> Amino Anthraquinones OR Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide Side Chain OR Non-covalent interaction >> DNA intercalation >> Fused-Ring Primary Aromatic Amines OR Non-covalent interaction >> DNA intercalation >> Quinones OR Radical OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Amino Anthraquinones OR Radical >> Radical mechanism via ROS formation (indirect) >> Fused-Ring Primary Aromatic Amines OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitroaniline Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR Radical >> Radical mechanism via ROS formation (indirect) >> p-Aminobiphenyl Analogs OR Radical >> Radical mechanism via ROS formation (indirect) >> Quinones OR Radical >> Radical mechanism via ROS formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines OR SN1 OR SN1 >> Carbenium ion formation OR SN1 >> Carbenium ion formation >> Alpha-Haloethers OR SN1 >> Nucleophilic attack after carbenium ion formation OR SN1 >> Nucleophilic attack after carbenium ion formation >> Specific Acetate Esters OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Amino Anthraquinones OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Fused-Ring Primary Aromatic Amines OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> p-Aminobiphenyl Analogs OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Single-Ring Substituted Primary Aromatic Amines OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitroaniline Derivatives OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR SN2 OR SN2 >> Acylation OR SN2 >> Acylation >> Specific Acetate Esters OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Specific Acetate Esters OR SN2 >> SN2 at sp3-carbon atom OR SN2 >> SN2 at sp3-carbon atom >> Alpha-Haloethers by DNA binding by OASIS v.1.3

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as No alert found AND SN1 AND SN1 >> Nitrenium Ion formation AND SN1 >> Nitrenium Ion formation >> Aromatic azo AND SN1 >> Nitrenium Ion formation >> Primary aromatic amine by DNA binding by OECD

Domain logical expression index: "h"

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 >> Hydroquinones OR SN1 >> Nitrenium Ion formation >> Aromatic nitro by DNA binding by OECD

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Non binder, non cyclic structure AND Strong binder, NH2 group by Estrogen Receptor Binding

Domain logical expression index: "j"

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

Domain logical expression index: "k"

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

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Ester aminolysis OR Acylation >> Ester aminolysis >> Amides OR SN2 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: "m"

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

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as SNAr OR SNAr >> Nucleophilic aromatic substitution OR SNAr >> Nucleophilic aromatic substitution >> Activated halo-benzenes by Protein binding by OECD

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as No superfragment by Superfragments ONLY

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as High (Class III) AND Low (Class I) by Toxic hazard classification by Cramer (original) ONLY

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Aliphatic acids and (Met)acrylic acids AND Aromatic amines by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as Sulfonic acids or their salts by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "s"

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 CN Aqueous Solubility < 0.1 g/L AND Group CN Vapour Pressure < 0.001 Pa by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as Group CN Melting Point > 180 C by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "u"

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 CN Aqueous Solubility < 0.1 g/L AND Group CN Vapour Pressure < 0.001 Pa by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "v"

Referential boundary: The target chemical should be classified as Group All Melting Point > 200 C by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "w"

Referential boundary: The target chemical should be classified as Acetoxy AND Aminoaniline, meta AND Aniline AND Aryl AND Azo AND Carboxylic acid by Organic Functional groups

Domain logical expression index: "x"

Referential boundary: The target chemical should be classified as Benzothiazole/ Benzoisothiazole by Organic Functional groups

Domain logical expression index: "y"

Referential boundary: The target chemical should be classified as Acetoxy AND Aminoaniline, meta AND Aryl AND Azo AND Carboxylic acid AND Overlapping groups by Organic Functional groups (nested)

Domain logical expression index: "z"

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

Domain logical expression index: "aa"

Referential boundary: The target chemical should be classified as Acid, aliphatic attach [-COOH] AND Alcohol, olefinic attach [-OH] AND Aliphatic Carbon [CH] AND Aliphatic Carbon [-CH2-] AND Aliphatic Carbon [-CH3] AND Aliphatic Nitrogen, one aromatic attach [-N] AND Aromatic Carbon [C] AND Azo [-N=N-] AND Carbonyl, aliphatic attach [-C(=O)-] AND Miscellaneous sulfide (=S) or oxide (=O) AND Olefinic carbon [=CH- or =C<] by Organic functional groups (US EPA)

Domain logical expression index: "ab"

Referential boundary: The target chemical should be classified as Aliphatic Oxygen, two aromatic attach [-O-] by Organic functional groups (US EPA)

Domain logical expression index: "ac"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.767

Domain logical expression index: "ad"

Parametric boundary:The target chemical should have a value of log Kow which is <= 4.1

Interpretation of results:

Category 1 (corrosive) based on GHS criteria

Conclusions:

4-(phenylazo)benzene-1,3-diamine acetate was estimated to be corrosive to the skin of New Zealand White rabbits.

Executive summary:

The dermal irritation potential of 4-(phenylazo)benzene-1,3-diamine acetate was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor.

4-(phenylazo)benzene-1,3-diamine acetate was estimated to be corrosive to the skin of New Zealand White rabbits.

Based on the estimated result; 4-(phenylazo)benzene-1,3-diamine acetate can be considered corrosive to skin and can be classified under the category “Category 1” as per CLP regulation.

Endpoint conclusion:

adverse effect observed (corrosive)

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 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 v 3.3

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material: 4-(phenylazo)benzene-1,3-diamine acetate
- IUPAC name: 4-(phenylazo)benzene-1,3-diamine acetate
- Molecular formula: C14H16N4O2
- Molecular weight: 272.306 g/mole
- Smiles Notation: c1(ccc(c(N)c1)\N=N\c1ccccc1)N.C(C)(=O)O
- InChl: 1S/C12H12N4.C2H4O2/c13-9-6-7-12(11(14)8-9)16-15-10-4-2-1-3-5-10;1-2(3)4/h1-8H,13-14H2;1H3,(H,3,4)/b16-15+;
- Substance type: Organic
- Physical state: Solid

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:

100 mg

Duration of treatment / exposure:

24 hours

Observation period (in vivo):

3 days

Number of animals or in vitro replicates:

2

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

72 h

Reversibility:

not specified

Remarks on result:

positive indication of irritation

Irritant / corrosive response data:

Signs of irritation observedThe ocular irritation potential of 4-(phenylazo)benzene-1,3-diamine acetate was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor.
4-(phenylazo)benzene-1,3-diamine acetate was estimated to be corrosive to the eyes of New Zealand White rabbits.
Based on the estimated result; 4-(phenylazo)benzene-1,3-diamine acetate can be considered corrosive to the eyes and can be classified under the category “Category 1” as per CLP regulation.

Estimation method: Takes mode value from the 6 nearest neighbours
Domain logical expression:Result: In Domain

(((((((((((((((("a" or "b" or "c" or "d" ) and ("e" and ( not "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 ( not "z") ) ) and ("aa" and ( not "ab") ) ) and ("ac" and ( not "ad") ) ) and ("ae" and ( not "af") ) ) and ("ag" and "ah" ) )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Anilines (Acute toxicity) AND Not categorized by US-EPA New Chemical Categories

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 azo AND SN1 >> Nitrenium Ion formation >> Primary aromatic amine 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 Anilines (amino-meta) AND Anilines (Unhindered) by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Non binder, non cyclic structure AND Strong binder, NH2 group by Estrogen Receptor Binding

Domain logical expression index: "f"

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

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Non binder, non cyclic structure AND Strong binder, NH2 group by Estrogen Receptor Binding

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Non binder, impaired OH or NH2 group by Estrogen Receptor Binding

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Non binder, non cyclic structure AND Strong binder, NH2 group by Estrogen Receptor Binding

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Non binder, MW>500 by Estrogen Receptor Binding

Domain logical expression index: "k"

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 CN Aqueous Solubility < 0.1 g/L by Eye irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as (!Undefined)Group CNHal Lipid Solubility < 400 g/kg by Eye irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "m"

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 CN Aqueous Solubility < 0.1 g/L by Eye irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "n"

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

Domain logical expression index: "o"

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 CN Aqueous Solubility < 0.1 g/L by Eye irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Group All log Kow < -3.1 by Eye irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Aliphatic acids and (Met)acrylic acids AND Aromatic amines by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as Sulfonic acids or their salts by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "s"

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

Domain logical expression index: "t"

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

Domain logical expression index: "u"

Referential boundary: The target chemical should be classified as Group 14 - Carbon C AND Group 15 - Nitrogen N AND Group 16 - Oxygen O by Chemical elements

Domain logical expression index: "v"

Referential boundary: The target chemical should be classified as Group 16 - Sulfur S by Chemical elements

Domain logical expression index: "w"

Referential boundary: The target chemical should be classified as Acetoxy AND Aminoaniline, meta AND Aniline AND Aryl AND Azo AND Carboxylic acid by Organic Functional groups

Domain logical expression index: "x"

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

Domain logical expression index: "y"

Referential boundary: The target chemical should be classified as Acetoxy AND Aminoaniline, meta AND Aniline AND Aryl AND Azo AND Carboxylic acid by Organic Functional groups

Domain logical expression index: "z"

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

Domain logical expression index: "aa"

Referential boundary: The target chemical should be classified as Acetoxy AND Aminoaniline, meta AND Aniline AND Aryl AND Azo AND Carboxylic acid by Organic Functional groups

Domain logical expression index: "ab"

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

Domain logical expression index: "ac"

Referential boundary: The target chemical should be classified as Acetoxy AND Aminoaniline, meta AND Aniline AND Aryl AND Azo AND Carboxylic acid by Organic Functional groups

Domain logical expression index: "ad"

Referential boundary: The target chemical should be classified as Carboxamide OR Carboxylic acid ester by Organic Functional groups

Domain logical expression index: "ae"

Referential boundary: The target chemical should be classified as Acetoxy AND Aminoaniline, meta AND Aniline AND Aryl AND Azo AND Carboxylic acid by Organic Functional groups

Domain logical expression index: "af"

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

Domain logical expression index: "ag"

Parametric boundary:The target chemical should have a value of log Kow which is >= -0.394

Domain logical expression index: "ah"

Parametric boundary:The target chemical should have a value of log Kow which is <= 4.1

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Conclusions:

4-(phenylazo)benzene-1,3-diamine acetate was estimated to be corrosive to the eyes of New Zealand White rabbits.

Executive summary:

The ocular irritation potential of 4-(phenylazo)benzene-1,3-diamine acetate was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor.

4-(phenylazo)benzene-1,3-diamine acetate was estimated to be corrosive to the eyes of New Zealand White rabbits.

Based on the estimated result; 4-(phenylazo)benzene-1,3-diamine acetate can be considered corrosive to the eyes and can be classified under the category “Category 1” as per CLP regulation.

Endpoint conclusion:

adverse effect observed (irreversible damage)

Endpoint conclusion:

no study available

Skin Irritation:

In different studies, 4-(phenylazo)benzene-1,3-diamine acetate has been investigated for potential for dermal irritation to a greater or lesser extent. The studies are based on in vivo experiments in rabbits, guinea pigs along with predicted data for target chemical and its structurally similar read across chemicals, 4-nitrobenzene-1,3-diamine[CAS: 5131-58-8] and 4-Methoxybenzylamine[CAS: 2393-23-9]. The predicted data using the OECD QSAR toolbox has also been compared with the experimental data.

The dermal irritation potential of 4-(phenylazo)benzene-1,3-diamine acetate was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor.

4-(phenylazo)benzene-1,3-diamine acetate was estimated to be corrosive to the skin of New Zealand White rabbits.

Based on the estimated result; 4-(phenylazo)benzene-1,3-diamine acetate can be considered corrosive to skin and can be classified under the category “Category 1” as per CLP regulation.

This is supported by an experimental study conducted(Sustainability Support Service (Europe) AB has Letter of Access,1982) on rabbits as per OECD Guideline 404 to determine the irritation potential of the structurally similar read across chemicals, 4-nitrobenzene-1,3-diamine[CAS: 5131-58-8].

The flank skin of 3 male New Zealand White rabbits was depilated on both sides on an area of approximately 6 x 6 cm with an electric clipper with suction for 24 hours before starting the test. In the experiment only animals with intact skin were taken. 0.5 g of 4 -nitro-m-phenylenediamine was applied under occlusion to clipped intact skin of the flank. The untreated side served as a control. The survey findings was performed 1, 24, 48 and 72 h after removal of the lobules and conclusion of the test after 10 test day. The stimulus values after 24 and 72 h were averaged over the experimental animals and dividing the resultant sum of the averages by 2.

After one hour, a yellowish discoloration of the skin was found. Discoloration held until the 9th day of the experiment at (Animal No. 4). The animals were followed up until the 10th day of the experiment.

The sum of the average stimulus values after 24 h (erythema = 1.3, edema = 0) and 72 h (erythema = 0.7, edema = 0) obtained by dividing by the number of these time points (by 2) gave a primary irritation score of 1.0.

From the above results, the classification of 4-nitro-m-phenylene diamine was considered to be irritating according to the E.C Commission's proposal on criteria for effects and irritants as set out in Annex VI II B 6 Directive.

The above results are further supported by the experimental study summarized in OTS0546455, NTRL report, 1992; for the structurally similar read across chemical, 4 -Methoxybenzylamine[CAS: 2393-23-9]. 4-Methoxybenzylamine was applied for 24 hour to the skin of 5 Hartley guinea pigs under occlusive conditions. The effects on skin were observed for 14 days. 4-Methoxybenzylamine caused erythema, edema, necrosis, and subsequent eschar formation at the site of application. The eschars persisted throughout the 14-day observation period.

Since the effects were persistent throughout the observation period, 4-Methoxybenzylamine was considered to be corrosive to skin.

Based on the available data for the target as well as read across chemicals and applying the weight of evidence approach, 4-(phenylazo)benzene-1,3-diamine acetate corrosive to skin. Comparing the above annotations with the criteria of CLP regulation, test chemical can be classified under the category “Category 1”.

Eye Irritation:

In different studies, 4-(phenylazo)benzene-1,3-diamine acetate has been investigated for potential for ocular irritation to a greater or lesser extent. The studies are based on in vivo experiments in rabbits along with predicted data for target chemical and its structurally similar read across chemical, 4-Methoxybenzylamine[CAS: 2393-23-9]. The predicted data using the OECD QSAR toolbox has also been compared with the experimental data.

The ocular irritation potential of 4-(phenylazo)benzene-1,3-diamine acetate was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor.

4-(phenylazo)benzene-1,3-diamine acetate was estimated to be corrosive to the eyes of New Zealand White rabbits.

Based on the estimated result; 4-(phenylazo)benzene-1,3-diamine acetate can be considered corrosive to the eyes and can be classified under the category “Category 1” as per CLP regulation.

This is supported by the experimental study summarized in OTS0546455, NTRL report, 1992; for the structurally similar read across chemical, 4-Methoxybenzylamine[CAS: 2393-23-9]. 0.1 ml of undiluted test chemical was instilled in to the eyes of 6 New Zealand White rabbits. 3 animals eyes were washed with distilled water and for 3 animals eyes were not washed out(duration not specified). The rabbits were observed for signs of irritation till 14 days.

4-Methoxybenzylamine caused strong edema, erythema, necrosis of the adnexal structures, corneal opacity, and discharge within one hour in both washed and unwashed eyes. The irises could not be evaluated due to the presence of extensive corneal opacity. The animals were euthanatized for humane reasons at the one-hour observation point.

Since the animals were killed before the end of observation period due to severity of the effects, 4-Methoxybenzylamine can be considered to be corrosive to rabbit eyes.

Based on the available data for the target as well as read across chemicals and applying the weight of evidence approach, 4-(phenylazo)benzene-1,3-diamine acetate corrosive to eyes. Comparing the above annotations with the criteria of CLP regulation, test chemical can be classified under the category “Category 1”.

Available data for 4-(phenylazo)benzene-1,3-diamine acetate indicates that it is likely to cause corrosion to eyes and skin.

Hence, 4-(phenylazo)benzene-1,3-diamine acetate can be classified under the category “Category 1” for skin and eye irritation as per CLP regulation.