Tripiperazine dicitrate

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

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:

equivalent or similar 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 effects of the test substance.

GLP compliance:

not specified

Test type:

other: Up and down procedure

Limit test:

no

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

Details on test material:

- Name of test material (as cited in study report): Piperazine citrate - Molecular formula: C12H30N6•Cl2H16O14 - Molecular weight: 642.76 g/mole - 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 citrate - Molecular formula: C12H30N6•Cl2H16O14 - Molecular weight: 642.76 g/mole - Substance type: Organic - Physical state: Solid

Test animals

Species:

other: Human

Strain:

other: not applicable

Sex:

female

Details on test animals or test system and environmental conditions:

- Age at study initiation: 42-year-old

Administration / exposure

Route of administration:

inhalation

Type of inhalation exposure:

whole body

Vehicle:

not specified

Details on inhalation exposure:

No data available

Analytical verification of test atmosphere concentrations:

not specified

Duration of exposure:

30 min

Concentrations:

0 and 5 mg/m3

No. of animals per sex per dose:

1 female

Control animals:

other: lactose powder was used as control substance

Details on study design:

- Duration of observation period following administration:3 hours - Frequency of observations and weighing: At intervals of 10 minutes for 30 minutes - Other examinations: Vital capacity of lung was measured. Parameters measure:FEV1 and FVC were measured at 5 and 10 minutes after inhalation of each concentration.

Statistics:

No data available

Results and discussion

Effect levels

Effect levels 1

Key result

Sex:

female

Dose descriptor:

LC50

Effect level:

> 5 mg/m³ air

Based on:

test mat.

Exp. duration:

30 min

Remarks on result:

other: No mortality , Effect on clinical sign.

Effect levels 2

Sex:

female

Dose descriptor:

other: EC

Effect level:

5 mg/m³ air

Based on:

test mat.

Exp. duration:

30 min

Remarks on result:

other: effect on clinical sign

Mortality:

No mortality observed in exposed woman.

Clinical signs:

other: cough, chest tightness, shortness of breath and wheezing as well as nasal stuffiness, watery nose, and nasal and ocular itching were observed in exposed woman.

Body weight:

No data available

Gross pathology:

No data available

Other findings:

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 in exposed woman.

Applicant's summary and conclusion

Interpretation of results:

other: not toxic

Conclusions:

LC50 was considered to be > 5 mg/m3 and EC was considered to be 5 mg/m3 when 42-year-old woman exposed to piperazine citrate. Thus, according to the CLP classification criteria the test material does not classify as acutely toxic by the inhaltion route.

Executive summary:

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.

At work, 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, several hours 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. LC50 was considered to be > 5 mg/m³and the Effect concentration (EC) for the test compound piperazine citrate is found to be 5 mg /m³when examined in a 42-year old woman. According to the publication, the test material is positive for effects after acute inhalation. However, according to the CLP classification criteria, the test material does not classify as acutely toxic by the inhaltion route.