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Toxicological information

Acute Toxicity: inhalation

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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

Constituent 1
Chemical structure
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 levelsopen allclose all
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.
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.

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