Registration Dossier

Skin Irritation:

The dermal irritation potential of 2-Hydroxypyridine 1-oxide was estimated using OECD QSAR toolbox v3.3 with logPow as the primary descriptor.

2-Hydroxypyridine 1-oxide was estimated to be highly irritating to the skin of New Zealand White rabbits. Based on the estimated results, 2-Hydroxypyridine 1-oxide can be considered to be highly irritating to skin and can be classified under the category “Category 2” as per CLP regulation.

Eye Irritation:

The ocular irritation potential of 2-Hydroxypyridine 1-oxide was estimated using OECD QSAR toolbox v3.3 with logPow as the primary descriptor.

2-Hydroxypyridine 1-oxide was estimated to be highly irritating causing irreversible damage to the eyes of New Zealand White rabbits.

Based on the estimated results, 2-Hydroxypyridine 1-oxide can be considered to be highly irritating to 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: 2-Hydroxypyridine 1-oxide
- Molecular formula: C5H5NO2
- Molecular weight: 111.1 g/mol
- Smiles notation: n1(c(O)cccc1)=O
- InChl : 1S/C5H5NO2/c7-5-3-1-2-4-6(5)8/h1-4,7H
- 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:

occlusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

no data available

Duration of treatment / exposure:

4 hours

Observation period:

24 and 72 hours

Number of animals:

3

Details on study design:

no data available

Other effects / acceptance of results:

no data available

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

72 h

Reversibility:

not specified

Remarks on result:

probability of severe irritation

Irritant / corrosive response data:

Severe irritation was observed

Estimation method: Takes mode value from the 9 nearest neighbours
Domain logical expression:Result: In Domain

((((((((((((((((((((((("a" or "b" or "c" or "d" or "e" ) and ("f" and ( not "g") ) ) and "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 "ad" ) and "ae" ) and "af" ) and "ag" ) and "ah" ) and "ai" ) and "aj" ) and "ak" ) and ("al" and "am" ) )

Domain logical expression index: "a"

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

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Aryl OR Heterocyclic Phenol OR N-Oxide OR Pyridine by Organic Functional groups ONLY

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Heterocyclic Phenol OR N-Oxide OR Overlapping groups by Organic Functional groups (nested) ONLY

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Alcohol, olefinic attach [-OH] OR Aromatic Carbon [C] OR Aromatic Nitrogen OR Hydroxy, aromatic attach [-OH] OR Miscellaneous sulfide (=S) or oxide (=O) OR Nitrogen oxide, aromatic nitrogen [n=O] OR Nitrogen oxide, aromatic nitrogen [n=O] non fused OR Olefinic carbon [=CH- or =C<] OR Oxygen, one aromatic attach [-O-] OR Pyridine, non fused rings by Organic functional groups (US EPA) ONLY

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Aromatic compound OR N-oxide OR Phenol by Organic functional groups, Norbert Haider (checkmol) ONLY

Domain logical expression index: "f"

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

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Michael-type addition, quinoid structures OR AN2 >> Michael-type addition, quinoid structures >> Quinoneimines OR AN2 >> Nucleophilic addition to alpha, beta-unsaturated carbonyl compounds OR AN2 >> Nucleophilic addition to alpha, beta-unsaturated carbonyl compounds >> alpha, beta-Unsaturated Aldehydes OR AN2 >> Schiff base formation OR AN2 >> Schiff base formation >> alpha, beta-Unsaturated Aldehydes OR Michael addition OR Michael addition >> Quinone type compounds OR Michael addition >> Quinone type compounds >> Quinone methides OR Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide Side Chain OR Non-covalent interaction >> DNA intercalation >> Fused-Ring Primary Aromatic Amines OR Radical OR Radical >> Radical mechanism by ROS formation OR Radical >> Radical mechanism by ROS formation >> Polynitroarenes OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Fused-Ring Primary Aromatic Amines OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitro Azoarenes OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitroaniline Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitroarenes with Other Active Groups OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR Radical >> Radical mechanism via ROS formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines OR Radical >> ROS formation after GSH depletion OR Radical >> ROS formation after GSH depletion (indirect) OR Radical >> ROS formation after GSH depletion (indirect) >> Quinoneimines OR Radical >> ROS formation after GSH depletion >> Quinone methides OR SN1 OR SN1 >> Alkylation after metabolically formed carbenium ion species OR SN1 >> Alkylation after metabolically formed carbenium ion species >> Polycyclic Aromatic Hydrocarbon Derivatives OR SN1 >> Nucleophilic attack after diazonium or carbenium ion formation OR SN1 >> Nucleophilic attack after diazonium or carbenium ion formation >> Nitroarenes with Other Active Groups OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Fused-Ring Primary Aromatic Amines 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 >> Nitro Azoarenes OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitroaniline Derivatives OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitroarenes with Other Active Groups OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Polynitroarenes OR SN2 OR SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation OR SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation >> Polycyclic Aromatic Hydrocarbon Derivatives OR SN2 >> Direct acting epoxides formed after metabolic activation OR SN2 >> Direct acting epoxides formed after metabolic activation >> Quinoline Derivatives OR SN2 >> DNA alkylation OR SN2 >> DNA alkylation >> Alkylphosphates, Alkylthiophosphates and Alkylphosphonates OR SN2 >> SN2 at an activated carbon atom OR SN2 >> SN2 at an activated carbon atom >> Quinoline Derivatives OR SN2 >> SN2 attack on activated carbon Csp3 or Csp2 OR SN2 >> SN2 attack on activated carbon Csp3 or Csp2 >> Nitroarenes with Other Active Groups by DNA binding by OASIS v.1.3

Domain logical expression index: "h"

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

Domain logical expression index: "i"

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

Domain logical expression index: "j"

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 Aromatic hydrocarbons (Liver enzyme induction) Rank C OR Benzene/ Naphthalene sulfonic acids (Less susceptible) Rank C OR Chlorphentermine (Hepatotoxicity) Alert OR Hydroquinones (Hepatotoxicity) Rank B OR Methyldopa (Hepatotoxicity) Alert OR Nitrophenols/ Halophenols (Energy metabolism dysfuntion) Rank B OR o-/ p-Aminophenols (Hemolytic anemia with methemoglobinemia) Rank B OR Oxyphenistain (Hepatotoxicity) Alert OR p-Alkylphenols (Hepatotoxicity) Rank A OR p-Aminophenols (Renal toxicity) Rank B OR Phenols (Mucous membrane irritation) Rank C OR Tamoxifen (Hepatotoxicity) Alert OR Thiocarbamates/Sulfides (Hepatotoxicity) No rank by Repeated dose (HESS)

Domain logical expression index: "k"

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: "l"

Referential boundary: The target chemical should be classified as Aldehydes OR Aromatic amines OR Ketones OR Phenols OR Sulfonic acids or their salts by Skin irritation/corrosion Inclusion 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 by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "n"

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 by Skin 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 by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "p"

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: "q"

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 by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as Group C 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 Melting Point > 180 C OR Group CN Vapour Pressure < 0.001 Pa by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "s"

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: "t"

Referential boundary: The target chemical should be classified as Group 3 - Lanthanoids by Chemical 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 14 - Metalloids Si,Ge by Chemical elements

Domain logical expression index: "w"

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: "x"

Referential boundary: The target chemical should be classified as Group 15 - Phosphorus P by Chemical elements

Domain logical expression index: "y"

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: "z"

Referential boundary: The target chemical should be classified as Group 2 - Alkaline Earth Be,Mg,Ca,Sr,Ba,Ra OR Group 4 - Trans.Metals Ti,Zr,Hf by Chemical elements

Domain logical expression index: "aa"

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: "ab"

Referential boundary: The target chemical should be classified as Group 5 - Trans.Metals V,Nb,Ta by Chemical elements

Domain logical expression index: "ac"

Referential boundary: The target chemical should be classified as Aryl AND Heterocyclic Phenol AND N-Oxide AND Pyridine by Organic Functional groups ONLY

Domain logical expression index: "ad"

Referential boundary: The target chemical should be classified as Aryl AND Heterocyclic Phenol AND N-Oxide AND Pyridine by Organic Functional groups ONLY

Domain logical expression index: "ae"

Referential boundary: The target chemical should be classified as Aryl AND Heterocyclic Phenol AND N-Oxide AND Pyridine by Organic Functional groups ONLY

Domain logical expression index: "af"

Referential boundary: The target chemical should be classified as Aryl AND Heterocyclic Phenol AND N-Oxide AND Pyridine by Organic Functional groups ONLY

Domain logical expression index: "ag"

Referential boundary: The target chemical should be classified as Aryl AND Heterocyclic Phenol AND N-Oxide AND Pyridine by Organic Functional groups ONLY

Domain logical expression index: "ah"

Referential boundary: The target chemical should be classified as Heterocyclic Phenol AND N-Oxide AND Overlapping groups by Organic Functional groups (nested) ONLY

Domain logical expression index: "ai"

Referential boundary: The target chemical should be classified as Aromatic compound AND N-oxide AND Phenol by Organic functional groups, Norbert Haider (checkmol) ONLY

Domain logical expression index: "aj"

Referential boundary: The target chemical should be classified as Aromatic compound AND N-oxide AND Phenol by Organic functional groups, Norbert Haider (checkmol) ONLY

Domain logical expression index: "ak"

Referential boundary: The target chemical should be classified as Alcohol, olefinic attach [-OH] AND Aromatic Carbon [C] AND Aromatic Nitrogen AND Hydroxy, aromatic attach [-OH] AND Miscellaneous sulfide (=S) or oxide (=O) AND Nitrogen oxide, aromatic nitrogen [n=O] AND Nitrogen oxide, aromatic nitrogen [n=O] non fused AND Olefinic carbon [=CH- or =C<] AND Oxygen, one aromatic attach [-O-] AND Pyridine, non fused rings by Organic functional groups (US EPA) ONLY

Domain logical expression index: "al"

Parametric boundary:The target chemical should have a value of log Kow which is >= -3.6

Domain logical expression index: "am"

Parametric boundary:The target chemical should have a value of log Kow which is <= 1.73

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Conclusions:

2-Hydroxypyridine 1-oxide was estimated to be highly irritating to the skin of New Zealand White rabbits.

Executive summary:

The dermal irritation potential of 2-Hydroxypyridine 1-oxide was estimated using OECD QSAR toolbox v3.3 with logPow as the primary descriptor.

2-Hydroxypyridine 1-oxide was estimated to be highly irritating to the skin of New Zealand White rabbits.

Based on the estimated results, 2-Hydroxypyridine 1-oxide can be considered to be highly irritating to skin and can be classified under the category “Category 2” as per CLP regulation.

Endpoint conclusion:

adverse effect observed (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 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: 2-Hydroxypyridine 1-oxide
- Molecular formula: C5H5NO2
- Molecular weight: 111.1 g/mol
- Smiles notation: n1(c(O)cccc1)=O
- InChl : 1S/C5H5NO2/c7-5-3-1-2-4-6(5)8/h1-4,7H
- 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:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

0.1ml

Duration of treatment / exposure:

single exposure

Observation period (in vivo):

24,48 and 72 hours

Duration of post- treatment incubation (in vitro):

no data available

Number of animals or in vitro replicates:

6

Details on study design:

no data available

Other effects / acceptance of results:

no data available

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

24/48/72 h

Reversibility:

not specified

Remarks on result:

positive indication of irritation

Irritant / corrosive response data:

Irritation was observed

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

(((((((((((((((((((((((("a" or "b" or "c" or "d" or "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 "v" ) and "w" ) and "x" ) and "y" ) and "z" ) and "aa" ) and ("ab" and ( not "ac") ) ) and ("ad" and ( not "ae") ) ) and ("af" and ( not "ag") ) ) and ("ah" and ( not "ai") ) ) and "aj" ) and "ak" ) and "al" ) and ("am" and "an" ) )

Domain logical expression index: "a"

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

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Aryl OR Heterocyclic Phenol OR N-Oxide OR Pyridine by Organic Functional groups ONLY

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Heterocyclic Phenol OR N-Oxide OR Overlapping groups by Organic Functional groups (nested) ONLY

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Alcohol, olefinic attach [-OH] OR Aromatic Carbon [C] OR Aromatic Nitrogen OR Hydroxy, aromatic attach [-OH] OR Miscellaneous sulfide (=S) or oxide (=O) OR Nitrogen oxide, aromatic nitrogen [n=O] OR Nitrogen oxide, aromatic nitrogen [n=O] non fused OR Olefinic carbon [=CH- or =C<] OR Oxygen, one aromatic attach [-O-] OR Pyridine, non fused rings by Organic functional groups (US EPA) ONLY

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Aromatic compound OR N-oxide OR Phenol by Organic functional groups, Norbert Haider (checkmol) ONLY

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 Group 14 - Carbon C AND Group 15 - Nitrogen N AND Group 16 - Oxygen O by Chemical elements

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Group 3 - Lanthanoids by Chemical elements

Domain logical expression index: "i"

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: "j"

Referential boundary: The target chemical should be classified as Group 9 - Trans.Metals Co,Rh,Ir by Chemical elements

Domain logical expression index: "k"

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: "l"

Referential boundary: The target chemical should be classified as Group 6 - Trans.Metals Cr,Mo,W OR Group 7 - Trans.Metals Mn,Tc,Re by Chemical elements

Domain logical expression index: "m"

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: "n"

Referential boundary: The target chemical should be classified as Group 4 - Trans.Metals Ti,Zr,Hf by Chemical elements

Domain logical expression index: "o"

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

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Halogens OR Metalloids by Groups of elements

Domain logical expression index: "q"

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: "r"

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

Domain logical expression index: "s"

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: "t"

Referential boundary: The target chemical should be classified as Group 15 - Phosphorus P by Chemical elements

Domain logical expression index: "u"

Referential boundary: The target chemical should be classified as Aryl AND Heterocyclic Phenol AND N-Oxide AND Pyridine by Organic Functional groups ONLY

Domain logical expression index: "v"

Referential boundary: The target chemical should be classified as Alcohol, olefinic attach [-OH] AND Aromatic Carbon [C] AND Aromatic Nitrogen AND Hydroxy, aromatic attach [-OH] AND Miscellaneous sulfide (=S) or oxide (=O) AND Nitrogen oxide, aromatic nitrogen [n=O] AND Nitrogen oxide, aromatic nitrogen [n=O] non fused AND Olefinic carbon [=CH- or =C<] AND Oxygen, one aromatic attach [-O-] AND Pyridine, non fused rings by Organic functional groups (US EPA) ONLY

Domain logical expression index: "w"

Referential boundary: The target chemical should be classified as Alcohol, olefinic attach [-OH] AND Aromatic Carbon [C] AND Aromatic Nitrogen AND Hydroxy, aromatic attach [-OH] AND Miscellaneous sulfide (=S) or oxide (=O) AND Nitrogen oxide, aromatic nitrogen [n=O] AND Nitrogen oxide, aromatic nitrogen [n=O] non fused AND Olefinic carbon [=CH- or =C<] AND Oxygen, one aromatic attach [-O-] AND Pyridine, non fused rings by Organic functional groups (US EPA) ONLY

Domain logical expression index: "x"

Referential boundary: The target chemical should be classified as Alcohol, olefinic attach [-OH] AND Aromatic Carbon [C] AND Aromatic Nitrogen AND Hydroxy, aromatic attach [-OH] AND Miscellaneous sulfide (=S) or oxide (=O) AND Nitrogen oxide, aromatic nitrogen [n=O] AND Nitrogen oxide, aromatic nitrogen [n=O] non fused AND Olefinic carbon [=CH- or =C<] AND Oxygen, one aromatic attach [-O-] AND Pyridine, non fused rings by Organic functional groups (US EPA) ONLY

Domain logical expression index: "y"

Referential boundary: The target chemical should be classified as Alcohol, olefinic attach [-OH] AND Aromatic Carbon [C] AND Aromatic Nitrogen AND Hydroxy, aromatic attach [-OH] AND Miscellaneous sulfide (=S) or oxide (=O) AND Nitrogen oxide, aromatic nitrogen [n=O] AND Nitrogen oxide, aromatic nitrogen [n=O] non fused AND Olefinic carbon [=CH- or =C<] AND Oxygen, one aromatic attach [-O-] AND Pyridine, non fused rings by Organic functional groups (US EPA) ONLY

Domain logical expression index: "z"

Referential boundary: The target chemical should be classified as Alcohol, olefinic attach [-OH] AND Aromatic Carbon [C] AND Aromatic Nitrogen AND Hydroxy, aromatic attach [-OH] AND Miscellaneous sulfide (=S) or oxide (=O) AND Nitrogen oxide, aromatic nitrogen [n=O] AND Nitrogen oxide, aromatic nitrogen [n=O] non fused AND Olefinic carbon [=CH- or =C<] AND Oxygen, one aromatic attach [-O-] AND Pyridine, non fused rings by Organic functional groups (US EPA) ONLY

Domain logical expression index: "aa"

Referential boundary: The target chemical should be classified as Alcohol, olefinic attach [-OH] AND Aromatic Carbon [C] AND Aromatic Nitrogen AND Hydroxy, aromatic attach [-OH] AND Miscellaneous sulfide (=S) or oxide (=O) AND Nitrogen oxide, aromatic nitrogen [n=O] AND Nitrogen oxide, aromatic nitrogen [n=O] non fused AND Olefinic carbon [=CH- or =C<] AND Oxygen, one aromatic attach [-O-] AND Pyridine, non fused rings by Organic functional groups (US EPA) ONLY

Domain logical expression index: "ab"

Referential boundary: The target chemical should be classified as Not possible to classify according to these rules by DPRA Lysine peptide depletion

Domain logical expression index: "ac"

Referential boundary: The target chemical should be classified as Low reactive OR Low reactive >> Epoxides OR Low reactive >> Short-chain alpha-alkyl cinnamaldehyde derivatives OR Moderate reactive OR Moderate reactive >> Cinnamaldehyde type compounds by DPRA Lysine peptide depletion

Domain logical expression index: "ad"

Referential boundary: The target chemical should be classified as Not possible to classify according to these rules by DPRA Cysteine peptide depletion

Domain logical expression index: "ae"

Referential boundary: The target chemical should be classified as High reactive OR High reactive >> alpha,beta-carbonyl compounds with polarized multiple bonds by DPRA Cysteine peptide depletion

Domain logical expression index: "af"

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

Domain logical expression index: "ag"

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 Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Hydroquinones OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Polycyclic (PAHs) and heterocyclic (HACs) aromatic hydrocarbons-Michael addition OR SN1 OR SN1 >> Carbenium Ion Formation OR SN1 >> Carbenium Ion Formation >> Polycyclic (PAHs) and heterocyclic (HACs) aromatic hydrocarbons-SN1 by DNA binding by OECD

Domain logical expression index: "ah"

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

Domain logical expression index: "ai"

Referential boundary: The target chemical should be classified as SN2 OR SN2 >> Direct acting epoxides formed after metabolic activation OR SN2 >> Direct acting epoxides formed after metabolic activation >> Quinoline Derivatives OR SN2 >> SN2 at an activated carbon atom OR SN2 >> SN2 at an activated carbon atom >> Quinoline Derivatives by DNA binding by OASIS v.1.3

Domain logical expression index: "aj"

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

Domain logical expression index: "ak"

Referential boundary: The target chemical should be classified as Aryl AND Heterocyclic Phenol AND N-Oxide AND Pyridine by Organic Functional groups ONLY

Domain logical expression index: "al"

Referential boundary: The target chemical should be classified as Aryl AND Heterocyclic Phenol AND N-Oxide AND Pyridine by Organic Functional groups ONLY

Domain logical expression index: "am"

Parametric boundary:The target chemical should have a value of log Kow which is >= -1.73

Domain logical expression index: "an"

Parametric boundary:The target chemical should have a value of log Kow which is <= 1.35

Interpretation of results:

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

Conclusions:

2-Hydroxypyridine 1-oxide was estimated to be highly irritating causing irreversible damage to the eyes of New Zealand White rabbits.

Executive summary:

The ocular irritation potential of 2-Hydroxypyridine 1-oxide was estimated using OECD QSAR toolbox v3.3 with logPow as the primary descriptor.

2-Hydroxypyridine 1-oxide was estimated to be highly irritating causing irreversible damage to the eyes of New Zealand White rabbits.

Based on the estimated results, 2-Hydroxypyridine 1-oxide can be considered to be highly irritating to 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:

Various studieshas been investigated for the test chemicalPyridin-2-ol 1-oxide (CAS No: 13161-30-3)to observe the potential for dermal irritation to a greater or lesser extent. The studies are based on in vivo experiments in rabbits and guinea pigs target chemicalPyridin-2-ol 1-oxide (CAS No: 13161-30-3) and its structurally similar read across substances3-methylpyridine (CAS No: 108-99-6 )and2-vinyl pyridine (CAS No: 100-69-6) .The predicted data using the OECD QSAR toolbox has also been compared with the experimental data and summarized as below;

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the skin irritation potential was estimated for test chemicalPyridin-2-ol 1-oxide (CAS No: 13161-30-3).The chemical Pyridin-2-ol 1-oxide (CAS No: 13161-30-3)is estimated to be highly irritating to skin of New Zealand White rabbits.

The U.S National Library of Medicine (2015) conducted the dermal irritation potential ofstructurally similar read across substance3-methylpyridine (CAS No: 108-99-6) in rabbits which supports the above mentioned result. Undiluted 3-methylpyridine was applied to the skin of male New Zealand albino rabbits and observed for signs of irritation till 7 or 14 days. Following 7 or 14 days rabbits were killed and histological examinations were performed on the test site.The skin irritation potential was characterized by cutaneous primary irritation index (PII). The Primary Irritation index (PII) for 3-methylpyridine was 6.8. Histological examination of the skin showed necrosis, ulceration and regeneration of tissues. Based on these observations, 3-methylpyridine can be considered to be severely irritating to rabbit skin.

The above results were further supported by the experimental study conducted by U.S. EPA (2009) ofstructurally similar read across substance2-vinyl pyridine (CAS No: 100-69-6) in guinea pigs. The undiluted 5, 2, 1, 0.5, 0.35, 0.2, 0.1, 0.05 mL/kg of 2-vinyl pyridine was applied under occlusion to the skin of guinea pigs for 24 hours. 10 guinea pigs per dose were used for the study. The guinea pigs were observed for signs of irritation and scored. Scoring was based onqualitative parameters of “slight, moderate, strong or severe”. All guinea pigs dosed with 5, 2, 1, 0.5 or 0.35 mL/kg of 2-vinyl pyridine died .Six of ten guinea pigs dosed with 0.2 mL/kg of 2-vinyl pyridine died. Only one guinea pig dosed with 0.1 or 0.05 ml/kg of 2-vinyl pyridine died. Based on these observations, 2-vinyl pyridine was considered to be a strong dermal irritant to guinea pig skin.

Thus on the basis of available data for thetarget chemicalPyridin-2-ol 1-oxide (CAS No: 13161-30-3) and its structurally similar read across substances3-methylpyridine (CAS No: 108-99-6 )and2-vinyl pyridine (CAS No: 100-69-6),it can be concluded thatchemical Pyridin-2-ol 1-oxide (CAS No: 13161-30-3) is able to cause skin irritation and considered as irritating.Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Category 2 (irritant)”.

Eye irritation:

In different studies,the test chemicalPyridin-2-ol 1-oxide (CAS No: 13161-30-3) has been investigated for potential for ocular irritationto a greater or lesser extent. The studies are based on in vivo experiments in rabbits for target chemicalPyridin-2-ol 1-oxide (CAS No: 13161-30-3) and its structurally similar read across substances3-methylpyridine (CAS No: 108-99-6)andPyridine (CAS NO: 110-86-1). The predicted data using the OECD QSAR toolbox has also been compared with the experimental data and summarized as below;

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the ocular irritation potential was estimated for test chemicalPyridin-2-ol 1-oxide (CAS No: 13161-30-3).The chemical Pyridin-2-ol 1-oxide (CAS No: 13161-30-3) is estimated to be severely irritating to eyes of New Zealand White rabbits.

The U.S National Library of Medicine (2015) conducted the ocular irritation potential ofstructurally similar read across substance3-methylpyridine (CAS No: 108-99-6) in rabbits which supports the above mentioned result. Undiluted 3-methylpyridine was applied to the eyes of male New Zealand albino rabbits and observed for signs of irritation till 7 or 14 days. Following 7 or 14 days rabbits were killed and histological examinations were performed on the eyes. Eye irritation was characterized by ocular irritation indices (OII). Eye irritation assessments showed that irritation was maximal either 1 hr or 1 day after exposure. Histological examination of the eyes showed keratitis lesions in corneal epithelial tissue, fibrillary edematous lamallae dissociation, and cellular inflammatory infiltration. Over longer periods of time, which included recovery, 3-methylpyridine was considered to be severely irritating and causes irreversible damage to rabbit eyes.

The above results were further supported by the experimental study conducted by the MAK Collection for Occupational Health and Safety (2012) forstructurally similar read across substance Pyridine (CAS NO: 110-86-1) in rabbits. The undiluted pyridine was instilled into the eyes of 6 male rabbits and observed for signs of irritation till 7 days. Irritation of the conjunctivae, inflammations of the iris and corneal turbidity occurred which was not reversible within 7 days. Based on these observations, pyridine was considered to be a highly irritating causing irreversible damage to rabbit eyes.

Thus on the basis of available data for thetarget chemicalPyridin-2-ol 1-oxide (CAS No: 13161-30-3) and its structurally similar read across substances3-methylpyridine (CAS No: 108-99-6)andPyridine (CAS NO: 110-86-1),it can be concluded thatchemical Pyridin-2-ol 1-oxide (CAS No: 13161-30-3) is able to cause irreversible ocular lesions and considered as eye irritating.Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category“Category 1”.

The skin and eye irritation potential of test chemicalPyridin-2-ol 1-oxide (CAS No: 13161-30-3) and its structurally similar read across substanceswere observed in various studies. The results obtained from these studies indicate that the chemicalPyridin-2-ol 1-oxideis likely to cause skin and eye irritation. HencePyridin-2-ol 1-oxide (CAS No: 13161-30-3)can be classified under the category “Category 2 (irritant)”for skin and“Category 1” foreye as per CLP.