Piperidin-4-ol

Endpoint summary

Description of key information

Skin irritation:

The dermal irritation potential of test chemical was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor. The test substance was estimated to be irritating into the skin of New Zealand White rabbits. Based on the estimated result test chemical can be considered to be irritating to skin and can be classified under the category ˋ“Category 2” as per CLP regulation.

 

Eye irritation:

The ocular irritation potential of Piperidin-4-ol (CAS No: 5382-16-1) was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor. The substance Piperidin-4-ol (CAS No: 5382-16-1) was estimated to be irritating into the eyes of Vienna White rabbits. Based on the estimated result Piperidin-4-ol (CAS No: 5382-16-1) can be considered to be irritating to eye and can be classified under the category ˋ“Category 1” as per CLP regulation.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

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 version 3.3 and QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: estimated data

Principles of method if other than guideline:

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

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material: 4-Hydroxypiperidine
- Molecular formula: C5H11NO
- Molecular weight: 101.148 g/mol
- Smiles notation: N1CCC(CC1)O
- InChl: 1S/C5H11NO/c7-5-1-3-6-4-2-5/h5-7H,1-4H2
- 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:

shaved

Vehicle:

not specified

Controls:

not specified

Amount / concentration applied:

No data available

Duration of treatment / exposure:

No data available

Observation period:

No data available

Number of animals:

No data available

Details on study design:

No data available

Irritation parameter:

overall irritation score

Basis:

mean

Reversibility:

not specified

Remarks on result:

positive indication of irritation

Irritant / corrosive response data:

Severe skin reactions were 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 ("f" and ( not "g") )  )  and ("h" and ( not "i") )  )  and "j" )  and "k" )  and "l" )  and "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 "aa" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Secondary amines by OECD HPV Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Aliphatic Amines by US-EPA New Chemical Categories

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Narcotic Amine by Acute aquatic toxicity MOA by OASIS

Domain logical expression index: "d"

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

Domain logical expression index: "e"

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

Domain logical expression index: "f"

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

Domain logical expression index: "g"

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

Domain logical expression index: "h"

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: "i"

Referential boundary: The target chemical should be classified as Group 15 - Phosphorus P OR Group 16 - Sulfur S by Chemical elements

Domain logical expression index: "j"

Similarity boundary:Target: OC1CCNCC1
Threshold=10%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "k"

Similarity boundary:Target: OC1CCNCC1
Threshold=30%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "l"

Similarity boundary:Target: OC1CCNCC1
Threshold=40%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "m"

Similarity boundary:Target: OC1CCNCC1
Threshold=60%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "n"

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

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Aliphatic amines (Mucous membrane irritation) Rank C OR Ethionine (Hepatotoxicity) Alert OR Perhexiline (Hepatotoxicity) Alert by Repeated dose (HESS)

Domain logical expression index: "p"

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: "q"

Referential boundary: The target chemical should be classified as Alkylalkanol-amines OR Aromatic amines OR Phenols OR Primary and secondary aliphatic amines by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "r"

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: "s"

Referential boundary: The target chemical should be classified as Group All Melting Point > 200 C OR Group CN Aqueous Solubility < 0.1 g/L OR Group CN Melting Point > 180 C OR Group CN Molecular Weight > 290 g/mol OR 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 No alert found by Respiratory sensitisation

Domain logical expression index: "u"

Referential boundary: The target chemical should be classified as Michael Addition OR Michael Addition >> Polarised alkenes OR Michael Addition >> Polarised alkenes >> Methacrylates OR Pro-Schiff base formation OR Pro-Schiff base formation >> Pro-cross linking Schiff base OR Pro-Schiff base formation >> Pro-cross linking Schiff base >> Ethanolamines by Respiratory sensitisation

Domain logical expression index: "v"

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: "w"

Referential boundary: The target chemical should be classified as Michael Addition OR Michael Addition >> Michael addition on conjugated systems with electron withdrawing group OR Michael Addition >> Michael addition on conjugated systems with electron withdrawing group >> alpha,beta-Carbonyl compounds with polarized double bonds  by Protein binding alerts for skin sensitization by OASIS v1.3

Domain logical expression index: "x"

Referential boundary: The target chemical should be classified as Not classified by Oncologic Primary Classification

Domain logical expression index: "y"

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

Domain logical expression index: "z"

Parametric boundary:The target chemical should have a value of log Kow which is >= -1.22

Domain logical expression index: "aa"

Parametric boundary:The target chemical should have a value of log Kow which is <= 0.332

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Conclusions:

The substance Piperidin-4-ol (CAS No: 5382-16-1) was estimated to be irritating into the skin of New Zealand White rabbits. Based on the estimated result Piperidin-4-ol (CAS No: 5382-16-1) can be considered to be irritating to skin.

Executive summary:

The dermal irritation potential of Piperidin-4-ol (CAS No: 5382-16-1) was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor. The substance Piperidin-4-ol (CAS No: 5382-16-1) was estimated to be irritating into the skin of New Zealand White rabbits. Based on the estimated result Piperidin-4-ol (CAS No: 5382-16-1) can be considered to be irritating to skin and can be classified under the category ˋ“Category 2” as per CLP regulation.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Link to relevant study records

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 version 3.3 and QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: Estimated data

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.3

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material: 4-Hydroxypiperidine
- Molecular formula: C5H11NO
- Molecular weight: 101.148 g/mol
- Smiles notation: N1CCC(CC1)O
- InChl: 1S/C5H11NO/c7-5-1-3-6-4-2-5/h5-7H,1-4H2
- Substance type: Organic
- Physical state: Solid

Species:

rabbit

Strain:

Vienna White

Details on test animals or tissues and environmental conditions:

No data available

Vehicle:

not specified

Controls:

not specified

Amount / concentration applied:

No data available

Duration of treatment / exposure:

24 hours

Observation period (in vivo):

8 days

Duration of post- treatment incubation (in vitro):

No data available

Number of animals or in vitro replicates:

2

Details on study design:

No data available

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 8 days

Reversibility:

not specified

Remarks on result:

positive indication of irritation

Irritant / corrosive response data:

Severe eye irritation was observed.

Estimation method: Takes mode value from the 8 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 ("x" and ( not "y") )  )  and ("z" and ( not "aa") )  )  and ("ab" and ( not "ac") )  )  and ("ad" and ( not "ae") )  )  and "af" )  and "ag" )  and ("ah" and "ai" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Secondary amines by OECD HPV Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Aliphatic Amines by US-EPA New Chemical Categories

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Narcotic Amine by Acute aquatic toxicity MOA by OASIS

Domain logical expression index: "d"

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

Domain logical expression index: "e"

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: "f"

Referential boundary: The target chemical should be classified as Alkylalkanol-amines OR Esters of organic sulfonic or sulfuric esters OR Ketones OR Phenols OR Primary and secondary aliphatic amines OR Sulfonic acids or their salts OR Tertiary aliphatic amine by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Lipid Solubility < 0.01 g/kg AND (!Undefined)Group CN Lipid Solubility < 0.4 g/kg by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as (!Undefined)Group C Surface Tension > 62 mN/m OR (!Undefined)Group CNHal Lipid Solubility < 4 g/kg OR (!Undefined)Group CNHal Lipid Solubility < 400 g/kg OR (!Undefined)Group CNS Surface Tension > 62 mN/m OR Exclusion rules not met OR Group All log Kow < -3.1 OR Group All log Kow > 9 OR Group All Melting Point > 200 C OR Group C Aqueous Solubility < 0.0001 g/L OR Group C Melting Point > 55 C OR Group C Vapour Pressure < 0.0001 Pa OR Group CN Aqueous Solubility < 0.0001 g/L OR Group CN Aqueous Solubility < 0.1 g/L OR Group CN log Kow > 4.5 OR Group CN log Kow > 5.5 OR Group CN Melting Point > 180 C OR Group CN Molecular Weight > 290 g/mol OR Group CN Molecular Weight > 540 g/mol OR Group CN Vapour Pressure < 0.001 Pa OR Group CNHal Aqueous Solubility < 0.001 g/L OR Group CNHal Aqueous Solubility < 0.1 g/L OR Group CNHal log Kow > 3.8 OR Group CNHal Molecular Weight > 370 g/mol OR Group CNHal Molecular Weight > 380 g/mol OR Group CNS log Kow < 0.5 OR Group CNS log Kow < -2 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: "i"

Referential boundary: The target chemical should be classified as No alert found by Protein binding alerts for Chromosomal aberration by OASIS v1.1

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Michael addition to alpha, beta-unsaturated acids and esters OR AN2 >> Michael addition to alpha, beta-unsaturated acids and esters >> alpha, beta - Unsaturated Carboxylic Acids and Esters by Protein binding alerts for Chromosomal aberration by OASIS v1.1

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Not classified by Oncologic Primary Classification

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Acrylamide Reactive Functional Groups OR Aromatic Amine Type Compounds OR C-Nitroso and Oxime Type Compounds OR Halogenated Aromatic Hydrocarbon Type Compounds OR Organophosphorus Type Compounds OR Siloxane Type Compounds by Oncologic Primary Classification

Domain logical expression index: "m"

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

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Derivatives of alpha amino benzene by Eye irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as No alert found by DNA alerts for AMES, MN and CA by OASIS v.1.3

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Carbamoylation after isocyanate formation OR AN2 >> Carbamoylation after isocyanate formation >> N-Hydroxylamines OR Radical OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> N-Hydroxylamines OR SN1 OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> N-Hydroxylamines by DNA alerts for AMES, MN and CA by OASIS v.1.3

Domain logical expression index: "q"

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: "r"

Referential boundary: The target chemical should be classified as Di-substituted hydrocarbons (24a) OR Di-substituted hydrocarbons (24c) OR Known precedent reproductive and developmental toxic potential OR Not covered by current version of the decision tree OR Organophosphorus compounds (1b) OR Piperazine-, dioxane-, morpholine-, tetrahydrothiopyran-like derivatives and cyclohexanamine (17c) by DART scheme v.1.0

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as No alert found by Carcinogenicity (genotox and nongenotox) alerts by ISS

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as Aliphatic N-nitro group (Genotox) OR Structural alert for genotoxic carcinogenicity OR Structural alert for nongenotoxic carcinogenicity OR Substituted n-alkylcarboxylic acids (Nongenotox) by Carcinogenicity (genotox and nongenotox) alerts by ISS

Domain logical expression index: "u"

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

Domain logical expression index: "v"

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

Domain logical expression index: "w"

Similarity boundary:Target: OC1CCNCC1
Threshold=50%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "x"

Referential boundary: The target chemical should be classified as Stable form by Tautomers unstable

Domain logical expression index: "y"

Referential boundary: The target chemical should be classified as Cyanamide form by Tautomers unstable

Domain logical expression index: "z"

Referential boundary: The target chemical should be classified as No alert found by in vivo mutagenicity (Micronucleus) alerts by ISS

Domain logical expression index: "aa"

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: "ab"

Referential boundary: The target chemical should be classified as Aliphatic alcohol  [-OH] AND Aliphatic amine   [-NH2  or  -NH-] AND -CH -  [cyclic] AND -CH2-  [cyclic] by Biodegradation fragments (BioWIN MITI)

Domain logical expression index: "ac"

Referential boundary: The target chemical should be classified as Cyanide / Nitriles   [-C#N] by Biodegradation fragments (BioWIN MITI)

Domain logical expression index: "ad"

Referential boundary: The target chemical should be classified as Aliphatic alcohol  [-OH] AND Aliphatic amine   [-NH2  or  -NH-] AND -CH -  [cyclic] AND -CH2-  [cyclic] by Biodegradation fragments (BioWIN MITI)

Domain logical expression index: "ae"

Referential boundary: The target chemical should be classified as Carbon with 4 single bonds & no hydrogens by Biodegradation fragments (BioWIN MITI)

Domain logical expression index: "af"

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

Domain logical expression index: "ag"

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

Domain logical expression index: "ah"

Parametric boundary:The target chemical should have a value of log Kow which is >= -0.942

Domain logical expression index: "ai"

Parametric boundary:The target chemical should have a value of log Kow which is <= 0.602

Interpretation of results:

Category 1 (irreversible effects on the eye)

Conclusions:

The substance Piperidin-4-ol (CAS No: 5382-16-1) was estimated to be irritating into the eyes of Vienna White rabbits. Based on the estimated result Piperidin-4-ol (CAS No: 5382-16-1) can be considered to be irritating to eye.

Executive summary:

The ocular irritation potential of Piperidin-4-ol (CAS No: 5382-16-1) was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor. The substance Piperidin-4-ol (CAS No: 5382-16-1) was estimated to be irritating into the eyes of Vienna White rabbits. Based on the estimated result Piperidin-4-ol (CAS No: 5382-16-1) can be considered to be irritating to eye and can be classified under the category ˋ“Category 1” as per CLP regulation.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation:

Various studies has been investigated for the test chemica to observe the potential for skin irritation to a greater or lesser extent. The studies are based on in vivo and in vitro experiments in rabbits for target chemical and its functionally similar read across substances.The predicted data using the OECD QSAR toolboxdatabasehas 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 chemical.The test chemical is estimated to be irritating to skin of New Zealand White rabbits.

 

The Henry F. Smyth Jr., Charles P. Carpenter, Carrol S. Well, Urbano C. Pozzani & Jean A. Striegel (1962) carried outacute dermal irritation study offunctionally similar read across substance1-methylpiperazine(CAS No: 109-01-3)in rabbits.Primary skin irritation on rabbits was recorded in a 10-grade ordinal series and was based upon the severest reaction that develops on the clipped abdominal skin of each of five albino rabbits within 24 hours of the uncovered application of 0.01 ml of undiluted sample or of solutions in water, propylene glycol, or acetone. Grade 1 indicates no irritation and Grade 2 the least visible capillary injection from the undiluted chemical. Grade 6 indicates necrosis when undiluted and Grade 10 indicates necrosis from a 0.01% solutionPrimary Irritation score after 24 hours for1-methylpiperazine was Grade 6. Based on this grade,test chemical can be considered moderatelyirritating to rabbit skin.

 

The above results were further supported by the experimental study conducted by European Chemicals Bureau (2005)in 3 (2 males and 1 female)Weisser Wienerwhite rabbits forfunctionally similar read across substance according to OECD Guideline 404. The rabbits were kept individually and the fur was removed by close clipping at least 15 hours pre dosing. About 500mg of piperazine in a 50% aqueous solution (assumingly piperazine base) was applied to a 6.25 cm2 gauze patch and applied to the skin and covered with a semi-occlusive dressing. After exposure for 4 hours, the test substance was removed, and the skin reaction evaluated after 30-60 minutes, 24, 48 and 72 hours, respectively. Observations at 48 and 72 hours revealedsevere erythema and necrosis in all animals. Hence the test chemical was considered as a strong skin irritant.

The dermal irritation potential of test article was determined according to the OECD 439 test guideline for this study. The MatTek EpiDerm™ model was used to assess the potential dermal irritation of the test article by determining the viability of the tissues following exposure to the test article via MTT. Tissues were exposed to the test article and controls for ~one hour, followed by a 42 hour post-exposure recovery period. The viability of each tissue was determined by MTT assay.The MTT data show the assay quality controls were met and passed the acceptance of criteria.The mean of OD for test chemical was determined to be 1.843 and 0.443 for 3 min. enpoint and 1 hour endpoint,respectively. The Mean % tissue viability compared to negative control (n=3) of the test chemical was determined to be 65.7% and 28.2% for 3 min. enpoint and 1 hour endpoint,respectively.Hence, under the current experimental test conditions it was concluded that test chemical was considered to be non-corrosive to human skin.

 

Based on the available data for the target as well as it read across substances and applying the weight of evidence approach, it can be concluded that test chemical was irritating to skin. Comparing the above annotations with the criteria of CLP regulation, test chemical can be classified under the category “Category 2”.

 

Eye Irritation:

In different studies, Piperidin-4-ol (CAS No: 5382-16-1) has been investigated for potential for ocular irritation to a greater or lesser extent.The studies are based on in vivo experiments in rabbits for target chemicalPiperidin-4-ol (CAS No: 5382-16-1) and its functionally similar read across substances1-methylpiperazine(CAS No: 109-01-3)andPiperazine (CAS No: 110-85-0).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 eye irritation potential was estimated for test chemicalPiperidin-4-ol (CAS No: 5382-16-1) .The chemical Piperidin-4-ol (CAS No: 5382-16-1) is estimated to be irritating to eye of Vienna White rabbits.

 

The Henry F. Smyth Jr., Charles P. Carpenter, Carrol S. Well, Urbano C. Pozzani & Jean A. Striegel (1962) carried outacute ocular irritation study offunctionally similar read across substance1-methylpiperazine(CAS No: 109-01-3)in rabbits.Eye injury in rabbits was recorded in a 10- grade ordinal series and was based upon the degree of corneal necrosis that results from instillation of various volumes and concentrations of chemical. Grade 1 indicates at most a very small area of necrosis resulting from 0.5 ml of undiluted chemical in the eye. Grade 5 indicates a so-called severe burn from 0.005 ml, and Grade 10 indicates a severe burn from 0.5 ml of a 1% solution in water or propylene glycol.Primary Eye Irritation score after 24 hours for1-methyl piperazinewas Grade 8.Based on the grade, 1-methyl piperazine(CAS No: 109-01-3)was considered to be severely irritating to eyes.

 

The above results were further supported by the experimental study conducted by IFA (GESTIS) (2017)in 3 (2 males and 1 female)Weisser Wienerwhite rabbits forfunctionally similar read across substancePiperazine (CAS No: 110-85-0).1 drop of the concentrated liquid (5 % solution) was instilled into rabbit eyes and effects were observed.1 drop of the concentrated liquid caused serious damage, which was considered persistent, to rabbits' eyes. Even an only 5 % solution caused damage which was assessed as grade 9 on a scale from 1 to 10. These effects were assessed to be corrosive in nature.Hence it was inferred that 5% or concentrated solution Piperazine causes severe irritation to rabbit eyes.

 

Based on the available data for the target as well as it read across substances and applying the weight of evidence approach, it can be concluded that Piperidin-4-ol (CAS No: 5382-16-1) was irritating to eyes. Comparing the above annotations with the criteria of CLP regulation, Piperidin-4-ol (CAS No: 5382-16-1) can be classified under the category “Category 1”. 

Justification for classification or non-classification

The skin and eye irritation potential of test chemicalPiperidin-4-ol (CAS No: 5382-16-1) and its functionally similar read across substanceswere observed in various studies. The results obtained from these studies indicate that the chemicalPiperidin-4-olis likely to cause skin and eye irritation. HencePiperidin-4-ol (CAS No: 5382-16-1)can be classified under the category“Category 2”for skin and“Category 1”eye as per CLP.