Piperidin-4-ol

Endpoint summary

Description of key information

LD50 was estimated to be 2655 mg/kg bw for rats.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

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 predicted using OECD QSAR toolbox version 3.3 and the supporting QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: as below

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.3

GLP compliance:

not specified

Test type:

other: not specified

Limit test:

no

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:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

not specified

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

not specified

Doses:

2655 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

not specified

Statistics:

not specified

Preliminary study:

not specified

Sex:

male/female

Dose descriptor:

LD50

Effect level:

2 655 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 50 % mortality observed

Mortality:

not specified

Clinical signs:

other: not specified

Gross pathology:

not specified

Other findings:

not specified

The prediction was based on dataset comprised from the following descriptors: LD50
Estimation method: Takes average 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 "i" )  and ("j" and ( not "k") )  )  and ("l" and ( not "m") )  )  and ("n" and ( not "o") )  )  and "p" )  and "q" )  and ("r" and "s" )  )

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 Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates >> Formamides 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 >> Carbenium Ion Formation OR SN1 >> Carbenium Ion Formation >> Allyl benzenes OR SN1 >> Iminium Ion Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines OR SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >> Aromatic azo OR SN1 >> Nitrenium Ion formation >> Aromatic nitro 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 >> 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 Class 5 (Not possible to classify according to these rules) by Acute aquatic toxicity classification by Verhaar (Modified) ONLY

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Very fast by Bioaccumulation - metabolism half-lives ONLY

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as No alert found by Respiratory sensitisation

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Pro-Michael Addition OR Pro-Michael Addition >> Pro-quinone and related OR Pro-Michael Addition >> Pro-quinone and related >> Phenylenediamines by Respiratory sensitisation

Domain logical expression index: "l"

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: "m"

Referential boundary: The target chemical should be classified as (!Undefined)Group CNS Surface Tension > 62 mN/m OR Exclusion rules not met OR Group All log Kow < -3.1 OR Group All Melting Point > 200 C OR Group CN Melting Point > 180 C OR Group CN Molecular Weight > 290 g/mol OR Group CN Vapour Pressure < 0.001 Pa 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: "n"

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: "o"

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

Domain logical expression index: "p"

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

Domain logical expression index: "q"

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

Domain logical expression index: "r"

Parametric boundary:The target chemical should have a value of log Kow which is >= -1.19

Domain logical expression index: "s"

Parametric boundary:The target chemical should have a value of log Kow which is <= -0.119

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

The LD50 was estimated to be 2655 mg/kg bw for rats.

Executive summary:

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute oral toxicity was estimated for 4-Hydroxypiperidine. The LD50 was estimated to be 2655 mg/kg bw for rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 655 mg/kg bw

Quality of whole database:

Data is Klimisch 2 and from OECD QSAR toolbox

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Acute oral toxicity:

In different studies, Piperidin-4-ol has been investigated for acute oral toxicity to a greater or lesser extent. Often are the studies based on in vivo experiments and estimated data in rodents, i.e. most commonly in mice and rats for Piperidin-4-ol along with the study available on structurally similar read across substance Diisopropanolamine (CAS no 110-97-4) and 2-Propanol, 1-amino- (CAS no 78-96-6). The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies.

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute oral toxicity was estimated for Piperidin-4-ol. The LD50 was estimated to be 2655 mg/kg bw for rats.

In another experimental study given by OECD SIDS (US/ICCA, SIAM 29, 20-22 October 2009) Diisopropanolamine (CAS no 110-97-4), rats were treated with Diisopropanolamine in the concentration of 2000 mg/kg orally.50 % mortality was observed at 2000 mg/kg. Therefore, LD50 was considered to be> 2000 mg/kg when rats were treated with Diisopropanolamine orally.

Further supported by experimental study given by OECD SIDS (US/ICCA, SIAM 29, 20-22 October 2009) on structurally similar read across substance 2-Propanol, 1-amino- (CAS no 78-96-6), rats were treated with 2-Propanol, 1-amino- in the concentration of 2813 mg/kg orally. 50 % mortality was observed at 2813 mg/kg. Therefore, LD50 was considered to be aprox 2813 mg/kg when rats were treated with 2-Propanol, 1-amino- orally.

Thus, based on the above studies and predictions on Piperidin-4-ol and its read across substances, it can be concluded that LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, Piperidin-4-ol can be classified as category V of acute oral toxicity.

Justification for classification or non-classification

Based on the above studies and predictions on Piperidin-4-ol and its read across substances, it can be concluded that LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, Piperidin-4-ol can be classified as category V of acute oral toxicity.