Piperazine, compound with phosphoric acid

Endpoint summary

Description of key information

From the data available, it is concluded that the chemical piperazine phosphate is strongly irritating to the skin and eyes. The harmonized classification of this chemical also supports this classification.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

4 (not assignable)

Qualifier:

according to guideline

Guideline:

other:

Principles of method if other than guideline:

Data is from The MAK Collection for Occupational Health and Safety

GLP compliance:

not specified

Species:

human

Strain:

not specified

Type of coverage:

not specified

Preparation of test site:

not specified

Vehicle:

other: unspecified

Irritation parameter:

erythema score

Basis:

mean

Reversibility:

no data

Remarks on result:

other: Irritating

Interpretation of results:

irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

A 37-year old woman developed urticaria and generalized erythema after treatment with various piperazine derivatives (citrate, phosphate) in succession

Executive summary:

A 37-year old woman developed urticaria and generalized erythema after treatment with various piperazine derivatives (citrate, phosphate) in succession

The other data that has been used for the weight for the weight of evidence approach is summarized below. From the eight of evidence, it is evident that the target chemical (CAS No 1951 -97 -9) as well as its parent chemical (CAS No 110 -85 -0) are positive skin irritants.

S. No	Result	Species	Source of data
1	Positive skin irritant (CAS No 1951-97-9)	Human (female)	Allergic reaction to piperazine. Med J Aust 1: 676
2	Positive skin irritant (CAS No 1951-97-9)	Details not available	QSAR predictions by Danish Environmental Protection Agency (EPA)model
3	Positive skin irritant (CAS No 110-85-0)	Rabbit	European Union Risk Assessment Report : Piperazine
4	Positive skin irritant (CAS No 110-85-0)	Human	Brit. J. Ind. Med.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

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. There are reliable reports indicating that phosphoric acid possesses properties indicating a hazard for human health (acute toxicity to respiratory tract, corrosivity to eye, and moderate repeated dose toxicity. However, based on the exposure data; the exposure to humans with phosphoric acid is expected to be minimal. Also, it is important to note that Piperazine by virtue of its highly basic nature shall exhibit more corrosive properties than phosphoric acid. Based on the above, it is has been considered that the properties of piperazine (parent molecule) shall have an important influence on the toxicological properties of piperazine phosphate. Thus, Piperazine (CAS No 110-85-0) has been used as a read across substance, especially for the toxicological end points in this dossier preparation.

Qualifier:

according to guideline

Guideline:

other:

Principles of method if other than guideline:

Data is from Am. J. Ophtalmol.

GLP compliance:

not specified

Species:

rabbit

Strain:

not specified

Vehicle:

other: sulphuric acid and ammonium hydroxide

Controls:

not specified

Amount / concentration applied:

0.005 ml of a 5% solution was applied

Duration of treatment / exposure:

24 hours

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 24

Score:

9

Max. score:

10

Reversibility:

not specified

Remarks on result:

other: caused etching and necrosis of the rabbit cornea

Interpretation of results:

irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

An aqueous solution containing 1-5% piperazine (assumingly piperazine base) caused etching and necrosis of the rabbit cornea.

Executive summary:

Normal rabbit eyes were selected on basis of visual inspection after staining with a 5% aqueous solution of fluorescein, and flushed out with distilled water 20 seconds after application. After a 2-hour resting period, 0.005 ml of a 5% solution was applied to the centre of the cornea while the lids were retracted. About one minute later the lids were released, and 18-24 hours later the eyes were stained with fluorescein and the injury scored.

Together with sulphuric acid and ammonium hydroxide, piperazine was given the grade 9 on a scale ranging from 1 to 10, with necrosis covering 60-90% of the cornea. An aqueous solution containing 1-5% piperazine (assumingly piperazine base) caused etching and necrosis of the rabbit cornea.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Additional information

From the data available, it is concluded that the chemical piperazine phosphate is strongly irritating to the skin and eyes. The harmonized classification of this chemical also supports this classification.

Justification for selection of skin irritation / corrosion endpoint:

Data is from an experimental studyand from an authoritative database. Also there are other data used in the weight of evidence that support the positive irritation potential of the chemical piperazine phosphate

Justification for selection of eye irritation endpoint:

Data belongs to the parent compound of piperazine phosphate

Effects on skin irritation/corrosion: irritating

Effects on eye irritation: irritating

Justification for classification or non-classification

Piperazine phosphate is strongly irritating to the skin and eyes. The harmonized classification of this chemical also supports this classification