Tripiperazine dicitrate

Endpoint summary

Description of key information

Short-term toxicity to fish:

Based on nominal concentration, experimental median lethal Concentrations [LC-50 (96 h)] for CAS No. -144-29-6 on Zebra fish (Danio rerio) was determined to be >100 mg/L. Based on this result it is concluded that the substance Piperazine citrate (CAS no. 144-29-6) does not qualify for the aquatic classification as per the CLP criteria.

Short term toxicity to aquatic invertebrates:

EC50 value of piperazine 2-hydroxypropane-1,2,3-tricarboxylate (3:2) (salt) (CAS:144-29-6) was estimated to be 218.80 mg/l for Daphnia magna after 48 hrs of duration, by QSAR toolbox. Thus based on this value it can be concluded that the substance can be considered as not classified as per the CLP regulation

Toxicity to aquatic algae and cyanobacteria:

After 72 hours of exposure to test item Tripiperazine dicitrate (CAS No. 144-29-6) to various nominal test concentrations, EC50 was found to be 87.912mg/l graphically and through probit analysis. Thus, based on the EC50 value, test substancecan be considered astoxic to aquatic organisms and thus can be classified as aquatic chronic category 3but since the substance is readily biodegradable and the partition coefficient (log Kow) of the test chemical is also not ≥ 4 (i.e, reported in range -1.15), test chemical can be considered as non-hazardous to aquatic algae and cyanobacteria as per the CLP criteria.

Toxicity to microorganisms:

EC0 was considered to be 200 mg/l when Gyrodactylus sp. infecting rainbow trout Oncorhynchus mykiss treated with Piperazine citrate. Based on this result it may be concluded that the substance Piperazine citrate (CAS no. 144-29-6) is non toxic to micro organisms.

Additional information

Short-term toxicity to fish:

Short term toxicity to fish was assessed for the target compound Piperazine citrate (CAS no. 144-29-6) and its related read- across by reviewing a number of studies. The summary of the results are presented below:

In key study, Fish Acute Toxicity test according to OECD Guideline 203 was conducted for the test substanceTripiperazine dicitrate (CAS 144 -29 -6). The nominal concentration selected for the experiment was 100mg/L and Zebra Fish (Danio rerio) were exposed to thisconcentration for 96 hours.

The lethal concentrations LC50 was found to be >100mg/L.

Supporting study from reviewed journal DISEASES OF AQUATIC ORGANISMS, Vol. 10: 39-43, 1991 indicate that the in – vivo toxicity study, Gyrodactylus sp. infecting rainbow trout Oncorhynchus mykiss treated with Piperazine citrate in the concentration of 0 and 200 mg/l. No effect were observed on Percentage of reduction and number of dead (immobile) rainbow trout Oncorhynchus mykiss fish. Therefore, EC0 was considered to be 200 mg/l when Gyrodactylus sp. infecting rainbow trout Oncorhynchus mykiss treated with Piperazine citrate.

 

Whereas read across substance Piperazine (Cas no. 110-85-0) from Data bank of Environmental Properties of Chemicals (EnviChem), 2016 indicate that Fish toxicity study was conducted for 48 hrs for evaluating the lethal concentration (LC50)of test substance Piperazine on fish Oryzias latipes on the basis of mortality effect. During experiment the lethal concentration (LC50) for test substance Piperazine was found to be >1000 mg/l.

Same read across from European Union Risk Assessment Report – PIPERAZINE, 3rd Priority List Volume: 56;Final Report, 2005 the test chemical Piperazine (Cas no. 110-85-0) indicate semi-static test according to OECD Guidelines 203 (Balk and Meuwsen, 1989b). The test medium was renewed after 48 hours. The nominal test concentrations were 180, 320, 560,1,000 and 1,800 mg/L. Test temperature was 22.3-23°C, pH of the test medium was neutralised to 7.0-7.3. Observations of mortality and sublethal effects among the fish (10 per test concentration) were performed at daily intervals during the test. LC50 could be determined to be>1, 800 mg/L.

 

Based on above results for target chemical and its read across it is concluded that the substance Piperazine citrate (CAS no. 144-29-6) does not qualify for the aquatic classification as per the CLP criteria.

Short term toxicity to aquatic invertebrates:

Predicted data of the test compound Piperazine Citrate and its read-across substance were reviewed from reliable sources for short term toxicity to aquatic invertebrates and are presented below as weight of evidence approach:

In key study, based on the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the five closest read across substances, the short term toxicity on aquatic invertebrates was predicted for piperazine 2-hydroxypropane-1,2,3-tricarboxylate (3:2) (salt) (CAS:144-29-6). EC50 value was estimated to be 218.80 mg/l for Daphnia magna after 48 hrs duration. Based on the value, the substance piperazine 2-hydroxypropane-1,2,3-tricarboxylate (3:2) (salt) is considered to be non-toxic to aquatic invertebrates and can be considered to be not classified as per the CLP regulations.

Supporting above prediction, 48 hrs aquatic toxicity study (Danish QSAR, 2016) was conducted to assess toxic effects of thePiperazine Citrate(CAS no 144-29-6) and the results were predicted. The study was based on the effects of the test compound on Daphnia magna in a static fresh water system. The predicted data suggests the effective concentration (EC50) for thePiperazine Citratewas estimated to be 213.4281 mg/l. 

Further, Short term toxicity to aquatic invertebrates test for read across piperazine (110-85-0) (J-check, 2013) was performed according to the OECD guideline 202.The test was conducted for 48 hrs and EC 50 value was observed. After experiment the EC50 value for short term toxicity to aquatic invertebrates for piperazine (110-85-0) was determined to be 110mg/l.

On the basis of results for toxicity to aquatic invertebrates for target and read across substance and by applying weight of evidence approoach, it can be considered that the substance is not likely to be toxic to aquatic invertebrates and can be considered as not classified as per the CLP regulation.

Toxicity to aquatic algae and cyanobacteria

Experimental key study for the test chemical Piperazine citrate (CAS No. 144-29-6) and supporting study for its related substance were reviewed to summarize the following information for toxicity to aquatic algae endpoint:

In key study, the effect of test item Tripiperazine dicitrate, CAS No. 144-29-6 was studied on the growth of fresh water green alga Chlorella vulgaris. The study was conducted following OECD guideline 201- Alga, growth inhibition test. The test concentration chosen for the study were 6.25mg/l, 12.5mg/l, 25mg/l, 50mg/l, 100mg/l and 200mg/l. The test concentrations were prepared using stock solution of the test item using mineral media. The green alga was exposed to the test concentration for a period of 72 hours to observe average specific growth rate and % growth inhibition under the effect of the test item. EC50 calculated graphically through probit analysis was observed to be 87.912mg/l.Thus, based on the EC50 value, test substancecan be considered astoxic to aquatic organisms and thus can be classified as aquatic chronic category 3 but since the substance is readily biodegradable and the partition coefficient (log Kow) of the test chemical is also not ≥ 4 (i.e, reported in range -1.15), test chemical can be considered as non-hazardous to aquatic organisms as per the CLP criteria.

Supporting above study, as per J-check database short term toxicity to algae study was carried out for 72 hrs for the structurally related substance piperazine (CAS 110 -85 -0). The study was performed according to OECD Guideline 201 (Alga, Growth Inhibition Test). On the basis of growth rate and AUG of the test organism algae,the 72 hrs EC50 values was determined to be 130 and 91 mg/l, respectively and NOEC values was determined to be 34 and 46 mg/l, respectively.Thus, based on the EC50 value (91 mg/l), it can be concluded that the substance can be considered as toxic to aquatic organisms and thus can be classified as aquatic chronic category 3 but since the read across substance is readily biodegradable, it can be considered as non-hazardous to aquatic organisms as per the CLP criteria.

Based on the overall reported results for target and read across substance, it can be concluded that the substancePiperazine citrate can be considered as non hazardous to aquatic algae and cyanobacteria as per the CLP criteria.

Toxicity to microorganisms:

Toxicity to micro organisms was assessed for the target compound Piperazine citrate (CAS no. 144-29-6) and its related read- across substance by reviewing a number of studies. The summary of the results are presented below as weight of evidence approach:

Key study from reviewed journal DISEASES OF AQUATIC ORGANISMS, Vol. 10: 39-43, 1991 indicate that thein - vitro toxicity study, Gyrodactylus sp. infecting rainbow trout Oncorhynchus mykiss treated with Piperazine citrate in the concentration of 0 and 200 mg/l. no effect were observed on Percentage of reduction and number of dead (immobile) Gyrodactylus salaries. Therefore, EC0 was considered to be 200 mg/l when Gyrodactylus sp. infecting rainbow trout Oncorhynchus mykiss treated with Piperazine citrate.

Various supporting studies of the read across compound piperazine (CAS no. 110-85-0) obtained from European Union Risk Assessment Report – PIPERAZINE, 3rd Priority List Volume: 56; final Report, 2005 were reviewed and are summarised as below:

The respiration inhibition of nitrifying bacteria was studied in a two hours study (Balk and Meuwsen, 1989c). No guidelines were referred to. The nominal test concentrations were 410,750 and 1,350 mg/L. The test temperature was 20°C, and the pH was kept neutral with HCl.

Further, the inhibition of cell multiplication of Pseudomonas putida was investigated during 18 hours in a study generally in accordance with an ISO Guideline (van Ginkel, 1989). The nominal test concentrations of piperazine were 62.5, 125, 250, 500 and 1,000 mg/L. Test temperature was 25°C, pH was adjusted to neutral by means of titration with H2SO4. Cell density was determined photometrically in single cultures at the beginning of the incubation and after 18 hours. No effect on cell multiplication was observed in any of the tested concentrations compared to the controls. NOEC was determined to be >1,000 mg/L (nominal concentration).

Similarly, an activated sludge respiration inhibition test was performed according to EEC Guidelines (OECD 209) (van Ginkel and Stroo, 1989). Homogenised sludge (0.46 g dw/L) was incubated at 20°C and pH 7.4-7.8 for 30 minutes with nominal test concentrations of 20, 60,180, 540 and 1,620 mg/L plus control. The oxygen depletion was measured in single samples using an oxygen electrode. At the highest test concentration, respiration inhibition was 16% compared to the control. NOEC was determined to be 540 mg/L.

Based on above results for target chemical as well as its read across substance and by applying weight of evidence approach it may be concluded that the substance Piperazine citrate (CAS no. 144-29-6) is non toxic to micro organisms.