Piperidin-4-ol

Endpoint summary

Description of key information

The skin sensitization potential of Piperidin-4-ol (CAS No: 5382-16-1) was estimated using OECD QSAR toolbox version 3.3 with log Pow as the primary descriptor. The substance Piperidin-4-ol (CAS No: 5382-16-1) was estimated to be not sensitizing to the skin of male Hartley guinea pigs. Based on the estimated result, Piperidin-4-ol (CAS No: 5382-16-1) failed to induce skin sanitization effects and hence is considered to be not sensitizing to Hartley guinea pigs.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Remarks:

in vivo

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with 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

Type of study:

Buehler test

Justification for non-LLNA method:

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:

guinea pig

Strain:

Hartley

Sex:

male

Details on test animals and environmental conditions:

No data available

Route:

epicutaneous, occlusive

Vehicle:

water

Concentration / amount:

No data available

Day(s)/duration:

No data available

Adequacy of induction:

not specified

Route:

epicutaneous, occlusive

Vehicle:

water

Concentration / amount:

No data available

Day(s)/duration:

No data available

Adequacy of challenge:

not specified

No. of animals per dose:

10

Details on study design:

No data available

Challenge controls:

No data available

Reading:

1st reading

Hours after challenge:

48

Group:

test chemical

Dose level:

No data available

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

No signs of skin sensitization was observed.

Remarks on result:

no indication of skin sensitisation

Cellular proliferation data / Observations:

No signs of skin sensitization was observed.

The prediction was based on dataset comprised from the following descriptors: "Skin Sensitisation"
Estimation method: Takes highest mode value from the 8 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 ("i" and ( not "j") )  )  and ("k" and ( not "l") )  )  and "m" )  and ("n" and "o" )  )

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 No alert found by DNA binding by OASIS v.1.3 ONLY

Domain logical expression index: "f"

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

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates >> Benzylamines-Acylation OR Michael addition OR Michael addition >> P450 Mediated Activation of Heterocyclic Ring Systems OR Michael addition >> P450 Mediated Activation of Heterocyclic Ring Systems >> Thiophenes-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 >> Alkyl phenols OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Arenes OR Michael addition >> Polarised Alkenes-Michael addition OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated amides OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated esters OR Schiff base formers OR Schiff base formers >> Chemicals Activated by P450 to Glyoxal  OR Schiff base formers >> Chemicals Activated by P450 to Glyoxal  >> Ethanolamines (including morpholine) OR Schiff base formers >> Chemicals Activated by P450 to Glyoxal  >> Ethylenediamines (including piperazine) OR Schiff base formers >> Chemicals Activated by P450 to Mono-aldehydes OR Schiff base formers >> Chemicals Activated by P450 to Mono-aldehydes >> Benzylamines-Schiff base OR Schiff base formers >> Direct Acting Schiff Base Formers OR Schiff base formers >> Direct Acting Schiff Base Formers >> Mono aldehydes OR SN1 OR SN1 >> Iminium Ion Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines OR SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >> Primary (unsaturated) heterocyclic amine OR SN1 >> Nitrenium Ion formation >> Tertiary (unsaturated) heterocyclic amine  OR SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine OR SN2 OR SN2 >> Epoxidation of Aliphatic Alkenes OR SN2 >> Epoxidation of Aliphatic Alkenes >> Halogenated polarised alkenes OR SN2 >> P450 Mediated Epoxidation OR SN2 >> P450 Mediated Epoxidation >> Thiophenes-SN2 by DNA binding by OECD

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as days - weeks by Biodeg ultimate (Biowin 3) ONLY

Domain logical expression index: "i"

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: "j"

Referential boundary: The target chemical should be classified as Alkyl amide, urea, thiourea, nitroso urea, carbonate, guanidine and carbamate derivatives (21b1) OR Alkyl amide, urea, thiourea, nitroso urea, carbonate, guanidine and carbamate derivatives (21b1) >> Alkylamide or thioamide analogs OR Di-substituted hydrocarbons (24a) OR Inorganic chemical OR Known precedent reproductive and developmental toxic potential OR Not covered by current version of the decision tree by DART scheme v.1.0

Domain logical expression index: "k"

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

Domain logical expression index: "l"

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

Domain logical expression index: "m"

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

Domain logical expression index: "n"

Parametric boundary:The target chemical should have a value of log Kow which is >= -3.84

Domain logical expression index: "o"

Parametric boundary:The target chemical should have a value of log Kow which is <= 2.78

Interpretation of results:

other: not sensitizing

Conclusions:

The substance Piperidin-4-ol (CAS No: 5382-16-1) was estimated to be not sensitizing to the skin of male Hartley guinea pigs. Based on the estimated result, Piperidin-4-ol (CAS No: 5382-16-1) failed to induce skin sanitization effects and hence is considered to be not sensitizing to Hartley guinea pigs.

Executive summary:

The skin sensitization potential of Piperidin-4-ol (CAS No: 5382-16-1) was estimated using OECD QSAR toolbox version 3.3 with log Pow as the primary descriptor. The substance Piperidin-4-ol (CAS No: 5382-16-1) was estimated to be not sensitizing to the skin of male Hartley guinea pigs. Based on the estimated result, Piperidin-4-ol (CAS No: 5382-16-1) failed to induce skin sanitization effects and hence is considered to be not sensitizing to Hartley guinea pigs.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Various studies has been investigated for the test chemical Piperidin-4-ol (CAS No: 5382-16-1) to observe the potential for skin sensitization to a greater or lesser extent. The studies are based on in vivo experiments in guinea pigs for target chemical Piperidin-4-ol (CAS No: 5382-16-1) and its closest read across substance with log Pow as the primary descriptor Dibutylamine (CAS no: 111-92-2) and Diisopropanolamine (CAS No: 110-97-4).The predicted data usingOECD QSAR toolbox database has also been compared with the experimental data and summarized as below;

 

The skin sensitization potential of Piperidin-4-ol (CAS No: 5382-16-1) was estimated using OECD QSAR toolbox version 3.3 with log Pow as the primary descriptor. The substance Piperidin-4-ol (CAS No: 5382-16-1) was estimated to be not sensitizing to the skin of male Hartley guinea pigs. Based on the estimated result, Piperidin-4-ol (CAS No: 5382-16-1) failed to induce skin sanitization effects and hence is considered to be not sensitizing to Hartley guinea pigs.

 

The HSDB database reported (2017) the dermal sensitization potential of read across substance Dibutylamine (CAS no: 111-92-2) in 10 CF1(BR) mice by using Mouse Ear Swelling Test (Sensitization Assay). Each mice was induced topically daily for 3 days at 0.1 ml s of a 0.1% (v/v in ethanol) test solution to clipped abdomens. A group of 10 mice likewise inducted over 3 days with 0.1 ml dermal applications of 0.5% (w/v) DNCB served as the positive control. inducted over 3 days with 0.1 ml dermal applications of 0.5% (w/v) DNCB served as Challenge and rechallenge were administered 7 and 14 days later in 0.01 ml dermal applications of a 25% (v/v) solution to both dorsal and ventral surfaces of the left and right ears respectively of inducted test mice. The thickness of treated left ears relative to that of solvent control (ethanol) right ears indicated the degree of sensitization. One animal challenged with di-n-butylamine exhibited a positive sensitization response (20% increase in ear thickness over control) at 48-hour evaluation only. None of either test or irritation control groups had responded to challenge by the 24-hour evaluation and none responded to rechallenge. Conversely, 60% and 50% positive response in the DCNB-inducted and challenged groups at 24-hour and 48-hour evaluations, respectively, confirmed the validity of the test system. Hence the chemical Dibutylamine (CAS no: 111-92-2) was considered as not skin sensitizing in Mouse Ear Swelling Test (Sensitization Assay).

 

The above results were further supported by the Buehler test conducted by IUCLID Dataset (2010) to assess the delayed contact hypersensitivity in ten male Hartley albino guinea pigs of read across substance Diisopropanolamine (CAS No: 110-97-4). Each guinea pig received three dermal applications of 0.4 ml of 50% DIPA in distilled water during the three-week induction period. The animals received one application of 0.4 ml of 50% DIPA during the challenge application two weeks after the last induction application. The condition of the test sites was assessed approximately 24 and 48 hours after the challenge application. Since no erythema was observed at the test site in any of the animals at the 48 hour read, the chemical Diisopropanolamine (CAS No: 110-97-4) was considered as not skin sensitizing to the skin of male Hartley albino guinea pigs.

 

 

Based on the available data for the target chemical, supporting studies and read across substance,it can be concluded thatchemical Piperidin-4-ol (CAS No: 5382-16-1) is unable to cause skin sensitization and considered as not sensitizing .Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

The skin sensitization potential of test substance Piperidin-4-ol (CAS No: 5382-16-1) and its closest read across substancewith log Pow as the primary descriptor Dibutylamine (CAS no: 111-92-2) and Diisopropanolamine (CAS No: 110-97-4) were observed in various studies. From the results obtained from these studies it is concluded that the chemical Piperidin-4-ol (CAS No: 5382-16-1) is not likely to cause skin sensitization and hence can be classified as non skin sensitizer.