Piperidin-4-ol

Endpoint summary

Description of key information

Short term toxicity to aquatic invertebrates:

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

Toxicity to aquatic algae and cyanobacteria:

The study was designed to assess the toxic effects of the test compound on the green alga Chlorella vulgaris. Test was conducted in compliance with the OECD guideline 201 (Alga, Growth Inhibition Test).

Test was carried out in 100mL conical flasks which were carefully autoclaved and sterilized. The test solution in each of these test vessels was kept constant which is 60 ml so that a sufficient amount of head space was left.The test item was prepared by adding 54.675 mg of test item in 250 ml of BBM to get the final concentration of 218.7 mg/L. This stock solution was kept for stirring for 02 minutes to obtain a homogenous solution for the experiment. The test concentrations were chosen according to the available data of the test item. The concentrations chosen were set up to the water solubility limit. The remaining test solutions were prepared by dilution from the above stock solution. To have a better growth and visibility of cells, the initial cell density of the culture was kept 1 X 104cells/ml. Care was taken to have a homogeneous solution for the experiment.

For the assessment of algal growth, the test was conducted in replicates. The control flask was maintained in triplicates as recommended in the OECD guideline and the test concentration were selected in geometric series which were maintained in duplicates. To obtain a quantitative concentration-response relationship by regression analysis, a linearizing transformation of the response data into probit was performed. Using the same, effective concentration (EC) were determined.

Algal growth was calculated daily by counting the cells microscopically with the help of haemocytometer. For microscopic observations the cultures were observed daily with the help of a microscope to verify a normal and healthy appearance of the algal culture and also to observe any abnormal appearance of the algae (as may be caused by the exposure of the test item). Apart from this, the cell count of each test vessel was also noted with the help of a microscope and haemocytometer. By spectrophotometer the absorbance values of each test vessel and control vessel was noted at 680nm.The BBM was taken as blank for both control and test vessels. The absorbance value of each vessel was in line with the average specific growth rate.

As per OECD 201, the biomass in the control cultures should have increased exponentially by a factor of at least 16 within the 72 hr test period. This corresponds to a specific growth rate of 0.92 per day. Thus, the observed specific growth rate in the control cultures during the experiment was 0.358 per day. Secondly the mean coefficient of variation for section by section specific growth rates (days 0-1, 1-2 & 2-3, for 72 hr tests) in the control cultures must not exceed 35%. Thus, the observed mean coefficient of variation in the control cultures during the experiment was 33.42%. Thirdly the coefficient of variation of average specific growth rates during the whole test period in replicate control cultures must not exceed 10%. Thus, the observed coefficient of variation of average specific growth rates during the experiment in control cultures was 8.26%. Hence, the test is considered valid as per OECD guideline, 201

The microscopic observations were also noted in each of the test vessel. All the cells appeared healthy, round and green throughout the study duration and no significant changes were observed up to the concentration of 218.7 mg/l. EC50 was found to be >200 mg/l graphically through probit analysis.

After 72 hours of exposure to test item to various nominal test concentrations, EC50 was determine to be >200 mg/l graphically and through probit analysis. Based on the EC50, it can be concluded that the chemical was not toxic to aquatic algae and can not be classified as per the CLP classification criteria.

Additional information

Summarized result of toxicity of the chemical Piperidin-4-ol (5382-16-1) on the growth of aquatic invertebrates and algae was studied by considering and collecting the data from various databases for target chemical. Some RA (read across) chemicals was also studied which was structurally and functionally similar to target chemical and also supporting the classification of chemical Piperidin-4-ol . The studies are as mention:

Short term toxicity to aquatic invertebrates:

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. The EC50 value was estimated to be 143.39 mg/l when Piperidin -4-olexposed 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.

Toxicity to aquatic algae and cyanobacteria:

The study was designed to assess the toxic effects of the test compound on the green alga Chlorella vulgaris. Test was conducted in compliance with the OECD guideline 201 (Alga, Growth Inhibition Test).

Test was carried out in 100mL conical flasks which were carefully autoclaved and sterilized. The test solution in each of these test vessels was kept constant which is 60 ml so that a sufficient amount of head space was left.The test item was prepared by adding 54.675 mg of test item in 250 ml of BBM to get the final concentration of 218.7 mg/L. This stock solution was kept for stirring for 02 minutes to obtain a homogenous solution for the experiment. The test concentrations were chosen according to the available data of the test item. The concentrations chosen were set up to the water solubility limit. The remaining test solutions were prepared by dilution from the above stock solution. To have a better growth and visibility of cells, the initial cell density of the culture was kept 1 X 104cells/ml. Care was taken to have a homogeneous solution for the experiment.

For the assessment of algal growth, the test was conducted in replicates. The control flask was maintained in triplicates as recommended in the OECD guideline and the test concentration were selected in geometric series which were maintained in duplicates. To obtain a quantitative concentration-response relationship by regression analysis, a linearizing transformation of the response data into probit was performed. Using the same, effective concentration (EC) were determined.

Algal growth was calculated daily by counting the cells microscopically with the help of haemocytometer. For microscopic observations the cultures were observed daily with the help of a microscope to verify a normal and healthy appearance of the algal culture and also to observe any abnormal appearance of the algae (as may be caused by the exposure of the test item). Apart from this, the cell count of each test vessel was also noted with the help of a microscope and haemocytometer. By spectrophotometer the absorbance values of each test vessel and control vessel was noted at 680nm.The BBM was taken as blank for both control and test vessels. The absorbance value of each vessel was in line with the average specific growth rate.

As per OECD 201, the biomass in the control cultures should have increased exponentially by a factor of at least 16 within the 72 hr test period. This corresponds to a specific growth rate of 0.92 per day. Thus, the observed specific growth rate in the control cultures during the experiment was 0.358 per day. Secondly the mean coefficient of variation for section by section specific growth rates (days 0-1, 1-2 & 2-3, for 72 hr tests) in the control cultures must not exceed 35%. Thus, the observed mean coefficient of variation in the control cultures during the experiment was 33.42%. Thirdly the coefficient of variation of average specific growth rates during the whole test period in replicate control cultures must not exceed 10%. Thus, the observed coefficient of variation of average specific growth rates during the experiment in control cultures was 8.26%. Hence, the test is considered valid as per OECD guideline, 201

The microscopic observations were also noted in each of the test vessel. All the cells appeared healthy, round and green throughout the study duration and no significant changes were observed up to the concentration of 218.7 mg/l. EC50 was found to be >200 mg/l graphically through probit analysis.

After 72 hours of exposure to test item to various nominal test concentrations, EC50 was determine to be >200 mg/l graphically and through probit analysis. Based on the EC50, it can be concluded that the chemical was not toxic to aquatic algae and can not be classified as per the CLP classification criteria.