Tripiperazine dicitrate

Respiratory sensitisation

Administrative data

Endpoint:

respiratory sensitisation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Justification for type of information:

Data is from peer reviewed journal

Data source

Reference

Reference Type:

publication

Title:

Occupational asthma due to piperazine citrate (Case Report)

Author:

S. Quirce1, R. Pelta2, J. Sastre1

Year:

2006

Bibliographic source:

J Investig Allergol Clin Immunol 2006; Vol. 16(2): 138-139

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: as mentioned below

Principles of method if other than guideline:

Inhalation effects of piperazine citrate was studied in a case report of 42-year old woman who had worked as a process operator in a chemical factory. A controlled specific inhalation challenge (SIC) test was carried out in a closed-circuit system to check the bronchial effects of the test substance.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Tripiperazine dicitrate

EC Number:

205-622-8

EC Name:

Tripiperazine dicitrate

Cas Number:

144-29-6

Molecular formula:

C6H8O7.3/2C4H10N2

IUPAC Name:

piperazine 2-hydroxypropane-1,2,3-tricarboxylate (3:2) (salt)

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report): Piperazine Citrate - Molecular formula (if other than submission substance): C12H30N6•Cl2H16O14 - Molecular weight (if other than submission substance): 642.76 g/mole - Smiles notation (if other than submission substance): C1CNCCN1.C1CNCCN1.C1CNCCN1.C(C(=O)O)C(CC(=O)O)(C(=O)O)O.C(C(=O)O)C(CC(=O)O)(C(=O)O)O - Substance type: Organic - Physical state: Solid-Purity:99.0% (BP)

Test animals

Species:

other: Human

Strain:

other: not applicable

Sex:

female

Details on test animals or test system and environmental conditions:

not specified

Test system

Route of induction exposure:

inhalation

Route of challenge exposure:

inhalation

Vehicle:

other: air

Concentration:

5 mg/m3

No. of animals per dose:

1

Details on study design:

RANGE FINDING TESTS: No MAIN STUDY A. INDUCTION EXPOSURE - No. of exposures: not specified - Exposure period: 30 min - Test groups: 1 - Control group: 1 - Site: nose - Frequency of applications: at intervals of 10 minutes - Duration: 3 hrs - Concentrations: total concentration of 5 mg/m3 B. CHALLENGE EXPOSURE - No. of exposures: 1 - Day(s) of challenge: 3 hours after 1st exposure - Exposure period: not specified - Test groups: 1 - Control group: 1 - Site: nose - Concentrations: not specified - Evaluation (hr after challenge): 24 hrs OTHER:

Challenge controls:

methacholine challenge

Positive control substance(s):

not specified

Negative control substance(s):

other: lactose powder (10 mg/m3 for 15 minutes)

Results and discussion

Results:

Specific inhalation challenge with piperazine citrate at a concentration of 5 mg/m3 for 30 minutes elicited an isolated late asthmatic response. Airway hyperresponsiveness to methacholine significantly increased 3 hours after the piperazine challenge, preceding the late asthmatic response.

Positive control results:

not specified

Negative control results:

no airway hyperresponsiveness to lactose powder exposure was observed.

Applicant's summary and conclusion

Interpretation of results:

Category 1 (respiratory sensitising) based on GHS criteria

Conclusions:

A 42 year old woman developed occupational asthma caused by piperazine citrate, as confirmed by the specific inhalation challenge test, possibly due to an immunological mechanism. Thus according to the CLP classification criteria, the test material classify as Respiratory sensitser under category 1 by the inhalation route.

Executive summary:

Inhalation effects of piperazine citrate were studied in a case report of 42-year old woman who had worked as a process operator in a chemical factory.

At work, she handled, weighed and packed several chemical products and drugs in batches. In 1995 she developed work-related symptoms of cough, chest tightness, shortness of breath and wheezing as well as nasal stuffiness, watery nose, and nasal and ocular itching. Her symptoms were mild and intermittent until October 1998, when she suffered from persistent asthma despite the fact that she wore a respirator at work. Asthma symptoms occurred mostly in the evening or at night, severalhours after her work shift. She noticed that these episodes developed after handling piperazine citrate. She was

symptom free during holidays and days off work. A controlled specific inhalation challenge (SIC) test was carried out in a closed-circuit system for exposure to particles as previously reported. The aerosol was inhaled by the patient at tidal volume. During aerosolization, powder concentration was measured in real time. As a control bronchial challenge the patient was exposed to lactose powder (10 mg/m3 for 15 minutes). The following day increasing concentrations of piperazine citrate powder were given by inhalation.She was exposed to 5mg/m³of the test compound Piperazine citrate. Skin prick test with piperazine citrate was positive. No mortality observed in exposed woman.Specific inhalation challenge with piperazine citrate at a concentration of 5 mg/m³for 30 minutes elicited an isolated late asthmatic response. Airway hyperresponsiveness to methacholine significantly increased 3 hours after the piperazine challenge, preceding the late asthmatic response. Thus according to the CLP classification criteria, the test material classify as Respiratory sensitser under category 1 by the inhalation route.