Tripiperazine dicitrate

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

Piperazine (CAS No 110-85-0) is the parent molecule from which piperazine citrate hase been prepared.

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, 1363-1372,1946

Reference 2

Reference Type:

secondary source

Title:

European Union Risk Assessment Report : Piperazine

Author:

European Chemicals Bureau

Year:

2005

Bibliographic source:

European Union Risk Assessment Report – PIPERAZINE, 3rd Priority List Volume: 56;Final Report, 2005; EUR 21642 EN

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: as mentioned below

Principles of method if other than guideline:

Eye irritation test of piperazine was conducted on rabbits.

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

Molecular formula:

C4H10N2

IUPAC Name:

Piperazine

Test material form:

solid: particulate/powder

Details on test material:

- Name of test material (as cited in study report):piperazine- Molecular formula :C4H10N2- Molecular weight:86.136 g/mol- Substance type:Organic- Physical State: Solid

Specific details on test material used for the study:

- Name of test material (as cited in study report): Piperazine- Molecular formula : C4H10N2- Molecular weight : 86.137 g/mole- Substance type:Organic- Physical state: Solid

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

Number of animals or in vitro replicates:

5

Details on study design:

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 scoredScoring System:Injury gradeDefinition10.5 ml. undiluted gives injury of 0 to 1.0 points20.5 ml. undiluted gives injury of over 1.0 up to 5.0 points30.1 ml. undiluted gives injury of up to 5.0 points (0.5 ml. gives over 5.0)40.02 ml. undiluted gives injury of up to 5.0 points (0.1 ml. gives over 5.0)50.005 ml. undiluted gives injury of up to 5.0 points (0.02 ml. gives over 5.0)6Excess of 40% solution gives injury of up to 5.0 points (0.005 ml. gives over 5.0)7Excess of 15% solution gives injury of up to 5.0 points (40% gives over 5.0)8Excess of 5% solution gives injury of up to 5.0 points (15% gives over 5.0)9Excess of 1% solution gives injury of up to 5.0 points (5% gives over 5.0)10Excess of 1% solution gives injury of over 5.0 points

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

Irritant / corrosive response data:

Together with sulphuric acid and ammonium hydroxide, piperazine was given the grade 9 on a scale ranging from 1 to 10, with necrosiscovering 60-90% of the cornea.

Applicant's summary and conclusion

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Conclusions:

An aqueous solution containing 1-5% piperazine (assumingly piperazine base) caused etching and necrosis of the rabbit cornea.Hence piperazine was considered to be irritating to rabbit eyes.

Executive summary:

An ocular irritation study was performed on rabbits to assess the irritation potency of the test chemical, piperazine.

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.

Hence piperazine was considered to be irritating to rabbit eyes.