Piperazine, compound with phosphoric acid

Endpoint summary

Description of key information

From the various data available, it has been concluded that the chemical piperazine phosphate is unlikely to exhibit actute toxicity by the oral, inhalation and the dermal route within the dose levels mentioned in the respective end points.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Qualifier:

according to guideline

Guideline:

other:

Principles of method if other than guideline:

The data is taken from jounal of American Medical Association.

GLP compliance:

not specified

Test type:

standard acute method

Species:

other: human

Strain:

not specified

Sex:

not specified

Route of administration:

oral: unspecified

Vehicle:

not specified

Sex:

not specified

Dose descriptor:

LD50

Effect level:

20 000 other: mg/kg

Based on:

test mat.

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The LD50 Value of Piperazine compound with phosphoric acid was found to be 20000 mg/kg in humans

Executive summary:

The LD50 Value of Piperazine compound with phosphoric acid was found to be 20000 mg/kg in humans.

The other data that has been used in the weight of evidence also suggest that the target chemical; piperazine phosphate is unlikely to exhibit acute oral toxicity within the dose levels mentioned below

S. No	Result	Species	Source of data
1	LD50 = 20000 mg/kg bw (CAS No 1951-97-9)	Human	TREATMENT OF ENTEROBIASIS AND ASCARIASIS WITH PIPERAZINE ,JAMA
2	LD50 = 20000 mg/kg bw (CAS No 1951-97-9)	Human	RTECS
3	LD50 = 22350 mg/kg bw  (CAS No 1951-97-9)	Mouse	Committee for Veterinary Medicinal Products - Piperazine - Summary report
4	LD50 = 2400 – 4300 mg/kg bw (CAS No 110-85-0)	Mouse	J. of Pharm. and Pharmacol. 6, 711-717.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

20 000 mg/kg bw

Quality of whole database:

Various available data indicate that the chemical; piperazine phosphate is unlikely to exhibit acute oral toxicity within the dose levels mentioned in the various studies

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Piperazine (CAS No 110-85-0) is the parent molecule from which piperazine, compound with phosphoric acid or piperazine phosphate (CAS No 1951-97-9) is synthesized. In medicine piperazine is used in the form of the hexahydrate or as the citrate, tartrate, phosphate (1951-97-9) or adipate. Thus, piperazine and piperazine phosphate can be considered as belonging to the same category.

Qualifier:

according to guideline

Guideline:

other:

Principles of method if other than guideline:

Standard method for inhalation toxicity

GLP compliance:

no

Test type:

other: 14 day study (test comp

Species:

rat

Strain:

not specified

Sex:

not specified

Route of administration:

inhalation: dust

Type of inhalation exposure:

whole body

Vehicle:

air

Details on inhalation exposure:

Piperazine chips were filled in a glass flask, and placed in a water bath at 20oC. Air was flown through the chips at a rate of 200 l per hour. The air stream, wit dust particles and volatile piperazine, was passed through glass chambers with rats, in total 12 animals. The exposure time was 3, 10, 30 minutes, 1, 3 or 7 hours. The animals were observed for 14 days after the test.

Duration of exposure:

> 2 - < 420 min

Concentrations:

Details not available

No. of animals per sex per dose:

Total number of animlas - 12

Control animals:

not specified

Details on study design:

Piperazine chips were filled in a glass flask, and placed in a water bath at 20oC. Air was flown through the chips at a rate of 200 l per hour. The air stream, with dust particles and volatile piperazine, was passed through glass chambers with rats, in total 12 animals. The exposure time was 3, 10, 30 minutes, 1, 3 or 7 hours. The animals were observed for 14 days after the test.

Sex:

male/female

Dose descriptor:

LC0

Effect level:

other: death and other respiratory irritation symptoms

Based on:

test mat.

Exp. duration:

7 h

Remarks on result:

other: No animals died and no symptoms were found at autopsy.

Mortality:

There was no mortality during the entire duration of test

Clinical signs:

other: No clinical symptoms observed at autopsy

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The chemical piperazine was not found to be acutely toxic by the inhalation route in the 7 hours study conducted with Rats

Executive summary:

The chemical piperazine was not found to be acutely toxic by the inhalation route in the 7 hours study conducted with Rats

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The chemical piperazine was not found to be acutely toxic by the inhalation route in the 7 hours study conducted with Rats

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Piperazine (CAS No 110-85-0) is the parent molecule from which piperazine, compound with phosphoric acid or piperazine phosphate (CAS No 1951-97-9) is synthesized. In medicine piperazine is used in the form of the hexahydrate or as the citrate, tartrate, phosphate (1951-97-9) or adipate. Thus, piperazine and piperazine phosphate can be considered as belonging to the same category.

Qualifier:

according to guideline

Guideline:

other:

Principles of method if other than guideline:

standard acute method

GLP compliance:

not specified

Test type:

standard acute method

Species:

rabbit

Strain:

not specified

Sex:

not specified

Type of coverage:

not specified

Vehicle:

not specified

Control animals:

not specified

Sex:

not specified

Dose descriptor:

LD50

Effect level:

4 000 mg/kg bw

Based on:

test mat.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute dermal median lethal dose (LD50) of Piperazine in rabbit was found to be 4000 mg/kg/bw.Acute toxicity of Piperazine to rabbit by the dermal route indicates that Piperazine does not exhibits acute toxicity by the dermal route within the doses mentioned.

Executive summary:

The acute dermal median lethal dose (LD50) of Piperazine in rabbit was found to be 4000 mg/kg/bw.Acute toxicity of Piperazine to rabbit by the dermal route indicates that Piperazine does not exhibits acute toxicity by the dermal route within the doses mentioned.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

4 000 mg/kg bw

Additional information

From the various data available, it has been concluded that the chemical piperazine phosphate is unlikely to exhibit actute toxicity by the oral, inhalation and the dermal route within the dose levels mentioned in the respective end points.

Justification for selection of acute toxicity – oral endpoint

Data is from an experimental study

Justification for selection of acute toxicity – inhalation endpoint

Data is from a reliable source

Justification for selection of acute toxicity – dermal endpoint

Data is from a reliable source

Justification for classification or non-classification

From the various data available, it has been concluded that the chemical piperazine phosphate is unlikely to exhibit actute toxicity by the oral, inhalation and the dermal route within the dose levels mentioned in the respective end points.