Piperidine

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1992

Report date:

1992

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EPA OTS 798.1175 (Acute Oral Toxicity)

Version / remarks:

July 1989

GLP compliance:

yes

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 (as cited in study report): Piperidine
- Physical state: Liquid, Colorless
- Analytical purity: no data
- Lot/batch No.: 20221AA
- Storage condition of test material: Room Temperature

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Wilmington, MA
- Age at study initiation: 49 to 74 days
- Weight at study initiation: 200 and 300 g
- Fasting period before study: overnight
- Housing: polycarbonate cages
- Diet: rodent ration (AgWay Prolab, Waverly, NY), ad libitum
- Water: tap water, ad libitum
- Acclimation period: 7 days (Range finding), four days (LD50)

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 30-70
- Air changes (per hr): 10 to 13
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Remarks:

USP

Details on oral exposure:

DOSAGE PREPARATION: Each dose preparation was placed on a magnetic stir plate and stirred for 10 minutes prior to dosing to ensure a homogenous solution

Doses:

Range Finding Trial: 2000, 1200, 800, 300, and 100 mg/kg
LD50 Trial: 300, 550 and 800 mg/kg

No. of animals per sex per dose:

in the range finding study one male, one female;
in the main study 5 animals per sex.

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: daily
- Frequency of weighing: day 0 (day of dosing), 7 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs

Statistics:

The LD50 was determined by the method of Linear Regression using the program "Linear Regression I" by R.J. Tallarida and R.B. Murray, (Manual of Pharmacologic Calculations with Computer Programs, Springer Verlag, New York, 1986, pp 10-13).

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

740 mg/kg bw

Based on:

test mat.

Mortality:

800 mg/kg: 1/5 males and 2/5 females died within 4 hours; 2/5 males died within one day and 2/5 females died within 6 days; in total 7/10 animals died.
550 mg/kg = 0/10
300 mg/kg = 0/10

Clinical signs:

other: 800 mg/kg: rats showed the following clinical signs during the observation period: catalepsy, tremors and lethargy. One surviving male appeared emaciated from day 7 to day 10. 550 mg/kg: clinical signs observed in rats included somnolence, catalepsy, let

Gross pathology:

800 mg/kg: Gross necropsy findings in rats of this dose group included haemorrhaging in the stomach and small intestines; adhesion of the stomach, small intestine and spleen to the abdominal cavity wall; brownish fluid in the abdominal cavity and discoloration of the kidneys.
550 mg/kg: Gross necropsy findings in rats of this dose group included adhesion of the stomach and spleen and thickening of the forestomach mucosa.
300 mg/kg: no signs of toxicity were observed at gross necropsy.

Other findings:

Range Finding:
Body Weights: All of the surviving animals gained body weight
Clinical Observations: The surviving animals did not show any clinical signs during the observation period.
Mortality: All animals of the dose groups 2000, 1200 and 800 mg/kg (one male and one female each) died within 4 hours after treatment. The animals in the two lowest dose group levels (300 and 100 mg/kg body weight) survived the entire observation period.
Necropsy: Animals that died during the study revealed signs of toxicity that included haemorrhaging in the stomach and the small and large intestine. No unusual lesions were noted in any of the surviving animals.
Based on the results of the Range Finding Study, the doses for the the LD50 determination study were selected to be 800, 550, and 300 mg/kg.

Any other information on results incl. tables

Table1 Acute oral toxicity.

 

Dose [mg/kg bw]	Mortality			Clinical signs
	N*	%	Time of death	N*	Duration
Males
800	3/5	60	4h / day 1	4/5	-
550	0/5	0	-	5/5	-
300	0/5	0	-	0/5	-
Females
800	4/5	80	4 h / day 6	3/5	-
550	0/5	0	-	5/5	-
300	0/5	0	-	0/5	-

*N= Number of animals/ number of animals used

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria