Piperidin-4-ol

Short-term toxicity to aquatic invertebrates

Link to relevant study record(s)

Reference

Endpoint:

short-term toxicity to aquatic invertebrates

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 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 the OECD 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

Analytical monitoring:

not specified

Vehicle:

not specified

Details on test solutions:

No data available

Test organisms (species):

Daphnia magna

Details on test organisms:

- Common name: Water flea

Test type:

static

Water media type:

freshwater

Total exposure duration:

48 h

Post exposure observation period:

No data available

Hardness:

250 ± 25 mg/L

Test temperature:

20 ± 2°C

pH:

7.8 ± 0.1

Dissolved oxygen:

No data available

Salinity:

No data available

Conductivity:

No data available

Nominal and measured concentrations:

No data available

Details on test conditions:

No data available

Reference substance (positive control):

not specified

Key result

Duration:

48 h

Dose descriptor:

EC50

Effect conc.:

143.395 mg/L

Nominal / measured:

estimated

Conc. based on:

test mat.

Basis for effect:

other: Intoxication

Remarks on result:

other: Nontoxic

Details on results:

No data available

Results with reference substance (positive control):

No data available

Reported statistics and error estimates:

No data available

The prediction was based on dataset comprised from the following descriptors: EC50
Estimation method: Takes average value from the 7 nearest neighbours
Domain  logical expression:Result: In Domain

(((((((((("a" or "b" or "c" or "d" )  and "e" )  and "f" )  and "g" )  and ("h" and ( not "i") )  )  and "j" )  and "k" )  and ("l" and ( not "m") )  )  and "n" )  and ("o" and "p" )  )

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 superfragment by Superfragments ONLY

Domain logical expression index: "g"

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

Domain logical expression index: "h"

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

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Benzodioxoles OR Nicotinoids by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "j"

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

Domain logical expression index: "k"

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

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 Group CN Aqueous Solubility < 0.1 g/L OR Group CN log Kow > 4.5 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: "n"

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

Domain logical expression index: "o"

Parametric boundary:The target chemical should have a value of log Kow which is >= -0.642

Domain logical expression index: "p"

Parametric boundary:The target chemical should have a value of log Kow which is <= 1.7

Validity criteria fulfilled:

not specified

Conclusions:

The EC50 value was estimated to be 143.39 mg/l when Piperidin-4-ol (IUPAC name:4-Hydroxypiperidine) exposed to daphnia magna for 48hrs.

Executive summary:

Based on the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the seven closest read across substances, toxicity on daphnia magna predicted for Piperidin-4-ol (IUPAC name:4-Hydroxypiperidine). The EC50 value was estimated to be 143.39 mg/l when Piperidin-4-ol exposed to daphnia magna for 48hrs.

Description of key information

Based on the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the seven closest read across substances, toxicity on daphnia magna predicted for Piperidin-4-ol. The EC50 value was estimated to be 143.39 mg/l when Piperidin-4-ol exposed to daphnia magna for 48hrs.

Key value for chemical safety assessment

Fresh water invertebrates

Fresh water invertebrates

Effect concentration:

143.39 mg/L

Additional information

Based on the various experimental data and prediction data for the target chemical as well as RA chemical which was selected on the basis of structure similarity study have been reviewed to determine the toxic nature of Piperidin-4-ol (5382-16-1) on the mobility of invertebrates. The studies are as mentioned below:

In the first weight of evidence study for target chemical Piperidin-4-ol (5382-16-1) from QSAR 2017, Based on the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the seven closest read across substances, toxicity on daphnia magna predicted for Piperidin-4-ol(IUPAC name:4-Hydroxypiperidine). The EC50 value was estimated to be 143.39 mg/l whenPiperidin-4-ol exposed to daphnia magna for 48hrs.

 

 

In the second weight of evidence study for the Piperidin-4-ol (5382-16-1) from ACD lab, ACD labs predicted median Lethal Concentration (LC50) of daphnia magna using v5.0.0.184. The value is supported by estimated Reliability Index (RI). Based on this, the LC 50 value for test item Piperidin-4-ol was predicted to be 540 mg/l for Daphnia magna. On the basis of predicted value it can be concluded that the substance Piperidin-4-ol is considered to be not toxic to aquatic environment and not classified as toxic as per the criteria mentioned in CLP regulation.

 

Similarly in the third weight of evidence studyfor the Piperidin-4-ol (5382-16-1) from EPISUITE 2017,. Based on the prediction done by EPI suite, ECOSAR version 1.1, on the basis of similarity of structure to chemicals for which the aquatic toxicity has been previously measured by structure-activity relationships (SARs) program, the LC 50 value for short term toxicity to aquatic invertebrates was predicted. On the basis of this program, the LC 50 value for short term toxicity to aquatic invertebrates was predicted to be 4898.511 mg/l for Piperidin-4-ol in 48 hrs. Based on this value it can be concluded that the substance Piperidin-4-ol is considered to be not toxic to aquatic environment and cannot be classified as toxic as per the criteria mentioned in CLP regulation.

 

 

Similarly in the fourth experimental study for the RA chemical (106-52-5) from ABITEC report 2017 selected on the basis of structure similarity Determination of the inhibition of the mobility of daphnids was carried out with the substance 1-methylpiperidin-4-ol according to OECD Guideline 202. The test substance was tested at the concentrations 0, 12, 25, 50, 100, 200 mg/L. Effects on immobilisation were observed for 48 hours. The median effective concentration (EC50) for the test substance, 1-methyl - piperidin-4-ol, in Daphnia magna was determined to be 113 mg/L for immobilisation effects, with the 95% CI of 97.8 -130.4 mg/l. This value indicates that the substance 1-methylpiperidin-4-ol is likely to be non-hazardous to aquatic invertebrates and cannot be classified as toxic as per the CLP criteria.

 

Similarly in the fifth weight of evidence study for another RA chemical (110 -85 -0) J-check, selected on the basis of functional similarity with the target chemical, Determination of short term toxicity of Piperazine on the mobility of daphnia was conducted for 48 hrs. Test was performed according to the standard OECD Guideline 202 (Daphnia sp. Acute Immobilisation Test). Based on the immobilization of daphnia species due to the exposure of chemical Piperazine, the EC50 was 110 mg/l. Thus it was concluded that the chemical was nontoxic and can be consider to be not classified as toxic as per the CLP classification criteria.

 

Based on the data from various sources, it can be concluded that the substance Piperidin-4-ol (5382-16-1) is considered to be not toxic to aquatic environment and cannot be classified as toxic as per the criteria mentioned in CLP regulation.