Piperidine

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:

comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1980

Report date:

1980

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

no

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Piperidine

EC Number:

203-813-0

EC Name:

Piperidine

Cas Number:

110-89-4

Molecular formula:

C5H11N

IUPAC Name:

piperidine

Specific details on test material used for the study:

- Name of test material: Piperidine
- Substanz-No.: 77/283
- Physical state: liquid, limpid
- Analytical purity: 99 %

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: WIGA, Sulzfeld, Germany
- Mean weight at study initiation: 185 ± 15 g,
- Housing: 5 animals per cage
- Diet: Herilan, mouse/rat/hamster maintenance diet; H. Eggersmann KG, Rinteln, Germany, ad libitum
- Water: Fully demineralized water each workday ad libitum; on holidays tap water ad libitum
- Acclimation period: at least one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 55 ± 5
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure system: Whole-body inhalation system (Groups of 5 animals are placed in wire cages which are located in a glass-steel inhalation chamber, V= 200 I.)
- Generator system: Continuous infusion pump UNITA I (B. Braun); Glass evaporator with thermostat (BASF).
By means of a continuous infusion pump, constant amounts of the test substance were supplied to an evaporator heated to 69°C .
The vapours that were formed were mixed with a flow of fresh air and passed into the inhalation chamber.
By means of an exhaust air system, the pressure ratios in the inhalation system were adjusted in such a way that there was a pressure slightly below
the atmospheric pressure (negative pressure). The inhalation mixture was offered to the animals for inhalation for 4 hours.

TEST ATMOSPHERE
- Brief description of analytical method used:
1. Equipment, chemicals and solutions: Gas chromatograph HP 5840 A
2. Sampling:
- Apparatus: two successive absorption vessels and downstream fritted flask
- Sorption solvent: xylene
- Sampling rate: 1 L
- Withdrawn amount: up to 10 L
- Sampling site: in the immediate vicinity of the noses of the animals
- Sampling probe diameter: 4 mm
3. Analytical test method: gas chromatography; piperidine was determined in xylene.

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

Nominal concentration [mg/L]: Group 1: 17.1; group 2: 7.7; group 3: 10.2; group 4: 5.1; group 5: 1.7
Analytical concentration [mg/L]: Group 1: 7.54; group 2: 5.30; group 3: 4.10; group 4: 2.80; group 5: 1.00

No. of animals per sex per dose:

10

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Weighing was done before treatment, after 7 days, after 14 days.
Observations were several times on the day of exposure and at least once daily afterwards.
- Necropsy of survivors performed: yes, animals were killed by C02 and similarly all animals deceased before scheduled sacrifice were necropsied.
- Other examinations performed: clinical signs and mortality: daily

Statistics:

The statistical evaluation of the study was carried out based on a probit analysis of DJ Finney (Finney, DJ; Probit Analysis 1971, pp 1-150.
Published by the Syndics of the Cambridge University Press, Bentley House, 200 Euston Road, London N.W. 1).

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

4.8 mg/L air (nominal)

Based on:

test mat.

Exp. duration:

4 h

Mortality:

Group 1:
males: 10 animals died (9 animals died within the day of exposure, 1 animal died within 5 days post exposure);
females: all animals (10) died within the day of exposure.
Group 2:
males: 6 animals died (3 animals died within the day of exposure, 1 on day 1, 4 and 5 after exposure, respectively);
females: 1 animal died (1 animal died on day 12 after exposure);
Group 3:
males: 3 animals died (1 animal died within the day of exposure, 1 on day 1 after exposure, and 1 on day 7 after exposure);
females: 7 animals died (1 animal died after day 1 of exposure, 1 on day 5, 6, 7, 11, respectively and 2 on day 8 after exposure);
Group 4:
males: no animal died;
females: 1 animal died (1 animal died on day 12 after exposure);
Group 5: no animal died.

Clinical signs:

other: Dose group 1, 2 and 3: severe watery nasal discharge; severe red discharge of the eyes; eyelid closure; nose wiping; cornea opacity; dyspnoea; tremor; clonic and jumping convulsions; abdominal and lateral position (experimental group 1 and 2); squatting

Body weight:

Mean body weight and body weight change (in parentheses):
Group 1: day 0: males: 186 g; females: 177 g;
Group 2: day 0: males: 181 g; females: 179 g; day 7: males: 161 (-20) g; females: 155 (- 24) g; day 14: males: 187 (+ 6) g; females: 174 (- 5) g;
Group 3: day 0: males: 184 g; females: 187 g; day 7: males: 176 (- 8) g; females: 145 (- 42) g; day 14: males: 207 (+ 23) g; females: 169 (- 18) g;
Group 4: day 0: males: 181 g; females: 179 g; day 7: males: 191 (+ 10) g; females: 163 (- 16) g; day 14: males: 229 (+ 48) g; females: 178 (- 1) g;
Group 5: day 0: males: 175 g; females: 182 g; day 7: males: 223 (+ 48) g; females: 197 (+ 15) g; day 14: males: 257 (+ 82) g; females: 205 (+ 23) g;
Control: day 0: males: 188 g; females: 178 g; day 7: males: 223 (+ 35) g; females: 198 (+ 20) g; day 14: males: 264 (+ 76) g; females: 208 (+ 30) g.
Compared to the control group, body weight gain in the treatment groups 2, 3 and 4 was considerably reduced, whereas the body weight gain of the treatment group 5 for the males was slighly enhanced and for the females slightly reduced.

Gross pathology:

Group 1: Heart: acute dilation of the atria, acute congestion hyperemia; lung: slight acute emphysema, weak pulmonary edema;
Group 2: Heart: acute dilation of the atria, acute congestion hyperemia; stomach/intestine bleedings; intestine, flatulence; pulmonary edema;
Group 3: Heart: acute dilation of the atria, acute congestion hyperemia; lung: slight acute emphysema, acute lobular pneumonia;
Group 4: no abnormalities detected; one animal haggard;
Group 5: no abnormalities detected.
In animals sacrificed at the end of the study no abnormalities were detected.

Applicant's summary and conclusion

Interpretation of results:

Category 3 based on GHS criteria