Piperazine, compound with phosphoric acid

Eye irritation

Administrative data

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.

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Chemical burns of the rabbit cornea.

Author:

Carpenter CP and Smyth HF

Year:

1946

Bibliographic source:

Am. J. Ophtalmol. 29, 1363-1372.

Reference 2

Reference Type:

other: study report

Title:

European Union Risk Assessment Report : Piperazine

Author:

European Chemicals Bureau

Year:

2005

Bibliographic source:

3rd Priority List Volume: 56;Final Report, 2005

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other:

Principles of method if other than guideline:

Data is from Am. J. Ophtalmol.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Piperazine

EC Number:

203-808-3

EC Name:

Piperazine

Cas Number:

110-85-0

IUPAC Name:

piperazine

Test animals / tissue source

Species:

rabbit

Strain:

not specified

Test system

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

Results and discussion

In vivo

Results

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

Applicant's summary and conclusion

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.