Pyrrolidine

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study with acceptable restrictions (used animals, limited documentation).

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1959

Report date:

1959

Reference 2

Reference Type:

secondary source

Title:

Unnamed

Year:

1959

Report date:

1977

Reference 3

Reference Type:

review article or handbook

Title:

Gesundheitsschaedliche Arbeitsstoffe, Toxikologisch-arbeitsmedizinische Begruendung von MAK-Werten (Maximale Arbeitsplatz-Konzentrationen), Pyrrolidin

Author:

MAK-Kommission

Year:

1977

Bibliographic source:

published in: VCH Weinheim, Germany, 20. Lieferung 1994

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

used animals

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Pyrrolidine

EC Number:

204-648-7

EC Name:

Pyrrolidine

Cas Number:

123-75-1

Molecular formula:

C4H9N

IUPAC Name:

pyrrolidine

Details on test material:

- Name of test material (as cited in study report): Pyrrolidin
- Physical state: liquid
- Analytical purity: 95 - 97 %

Test animals

Species:

rat

Strain:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: breeder
- Weight at study initiation: females: 152 - 230 g; males: 154 - 252 g

ENVIRONMENTAL CONDITIONS
- No data

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: The doses were applied as 1 % or 10 % preparations of the test substance in aqua dest.
- Justification for choice of vehicle: soluble in water

MAXIMUM DOSE VOLUME APPLIED: 20 mL/kg

Doses:

200, 400, 500, 640 and 1600 µL/kg bw (corresponding to approx. 172, 344, 430, 550, 1374 mg/kg bw; calculation based on density of 0.859 g/cm³)

No. of animals per sex per dose:

172 mg/kg bw: 3 females, 2 males; 344 mg/kg bw: 5 females; 430 mg/kg bw: 5 females and 5 males; 550 mg/kg bw: 5 females; 1374 mg/kg bw: 3 females.

Control animals:

no

Details on study design:

- Duration of observation period following administration: 7 days
- Frequency of observations and weighing: Body weight was determined before the beginning of the study for dose calculation. Observation of clinical signs was determined several times on the day of administration and once daily afterwards with the exception of weekends and on holidays.
- Necropsy of survivors performed: yes, at 344 mg/kg bw and higher concentrations. No necropsy was done at 172 mg/kg bw.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

430 mg/kg bw

Based on:

test mat.

Remarks on result:

other: The original value 0.5 mL/kg was converted to mg/kg body weight using the density of 0.859 g/cm³

Mortality:

Results are given as dead animals/total number of animals:
172 mg/kg bw: females: 0/3; males: 0/2
344 mg/kg bw: females: 1/5 (one day after treatment).
430 mg/kg bw: females: 0/5; males: 4/5 (one animal on the day of treatment, one animal on day 2, 3 and 6 after treatment, respectively)
550 mg/kg bw: females: 5/5 (3 within 10 min after treatment; one on day 4 and 5 after treatment, respectively)
1374 mg/kg bw: females: 3/3 (on the day of treatment)

Clinical signs:

172 and 322 mg/kg bw: females: accelerated respiration after treatment; one day after treatment no abnormality detected.
430, 550, 1374 mg/kg bw: after treatment: hindered respiration; latero-abdominal position; apathy; flaccid tonus. The next day at the nose and eyes of the animals bloody crust formation. No food intake after treatment. Surviving animals show food intake 4 days after treatment.

Body weight:

No data about body weight gain.

Gross pathology:

Deceased animals:
344 mg/kg bw: females: no abnormality detected.
430 mg/kg bw: females: chemical burns to the stomach and duodenum; gastro-intestinal vessels strongly injected; focal pneumonia; hemothorax, fragile, thickened stomach wall, partly conjoined with the peritoneum.
550 mg/kg bw: no abnormality detected.
1374 mg/kg bw: gastro-intestinal chemical burns; vessels strongly injected.
Sacrifized animals:
430 mg/kg bw: hydrothorax; extensive adhesions between stomach, liver and spleen; gastritis, gastric wall thickened.
344 mg/kg bw: gastritis

Any other information on results incl. tables

Table1. Acute oral toxicity.

 

Dose [mg/kg bw]	Mortality
	N*	%	Time of death
Males
172	0/2	0	-
344	n.d.	-	-
430	4/5	80	Day 1, 2, 3, and 6, one animal each day.
550	n.d.	-
1374	n.d.	-
Females
172	0/3	0	-
344	1/5	20	Day 2
430	0/5	0	-
550	5/5	100	3 within 10 min, on day 4 and 5, one animal each
1374	3/3	100	Day 1

N= Number of animals/ number of animals used; n.d.: not determined.

 

Applicant's summary and conclusion

Conclusions:

Under the conditions of this study the LD50 for male and female rats after oral application was determined to be 430 mg/kg bw.

Executive summary:

In principle, the methods described in OECD Guideline 401 were used in this study. Young adult laboratory rats were purchased from breeder. Several groups of rats were treated simultaneously by gavage with preparations of the test substance in water. The concentrations of these preparations were used to achieve comparable volumes per kg body weight. Group-wise documentation of clinical signs was performed over the 7-day study period. Body weight was determined before the start of the study only, as it was needed for determination of dose.

The following clinical signs were observed: accelerated respiration, hindered respiration, latero-abdominal position, apathy, flaccid tonus, bloody crust formation at noses and eyes, and no food intake for several days after treatment.

At necropsy, the following observations were made in deceased animals: chemical burns to the stomach and duodenum, strongly injected gastro-intestinal vessels, focal pneumonia, hemothorax, and fragile, thickened stomach wall, partly conjoined with the peritoneum.

The LD50 for male and female rats after oral application was determined to be 430 mg/kg bw.