2-pyrrolidone

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1998-11-30 to 1998-12-17

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study performed according to OECD guideline 401 and EU Method B1 with acceptable restriction which do not impair the overall conclusion from the data (purity of the test item is missing).

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1999

Report date:

1999

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

1) No 95%-CI for LD50; 2) No dose-mortality curve and slope

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes (incl. QA statement)

Remarks:

The Departement of health of the Goverment of the UK

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2-pyrrolidone

EC Number:

210-483-1

EC Name:

2-pyrrolidone

Cas Number:

616-45-5

Molecular formula:

C4H7NO

IUPAC Name:

pyrrolidin-2-one

Details on test material:

- Name of test material: 2-pyrrolidone
- Substance type: no data - identity,
- Analytical purity: purity (Sponsor responsibility)
- Stability under test conditions: stability (responsibility of the Sponsor)
- Physical state: colourless liquid
- Analytical purity: no data
- Expiration date of the lot/batch: no data
- Storage condition of test material: at room temperature in the dark

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 (UK) Ltd., Margate, Kent, UK
- Age at study initiation: 8-12 weeks
- Weight at study initiation: males: 211-235 g/females: 200-225 g
- Fasting period before study: overnight
- Housing: groups of 5 by sex in solid-floor polypropylene cages furnished with woodflakes
- Diet: ad libitum Rat and Mouse expanded diet no. 1 (special diets services limited, Witham, Essex, UK)
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-21 deg C
- Humidity (%): 44-67 %
- Air changes (per hr): 15 air changes per hr
- Photoperiod (hrs dark / hrs light): 12 hrs dark / 12 hrs light

IN-LIFE DATES: From: no data To: no data

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED:
1.81 mL/kg (range finding study)

Doses:

2000 mg/kg bw (male, female)

No. of animals per sex per dose:

5 males dosed 2000 mg/kg bw
5 females dosed 2000 mg/kg bw

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations 0.5, 1, 2, 4 h after dosing and once daily for 14 days/ weighing prior to dosing on day 0 and on days 7 and 14
- Necropsy of survivors performed: yes (at the end of the study the animals were killed by cervical dislocation and subjected to gross pathatological examination)
- Other examinations performed: clinical signs (hunched posture), body weight, histopathology (external examination, opening of abdominal and thoracic cavities for examination of major organs)

Statistics:

no data

Results and discussion

Preliminary study:

Range-finding test with 1 male and 1 female dosed once orally with 2 g/kg revealed reversible clinical effects (hunched posture) 2 days post-dosing

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

no deaths

Clinical signs:

other: Incidents of hunched posture were noted in all treated animals during the day of dosing and persisted in one male on Day 1. All animals appeared normal two days after treatment (Table 1 in "Remarks on results")

Gross pathology:

no abnormalities

Other findings:

no data

Any other information on results incl. tables

Table 1: Individual Clinical Observations and Mortality Data

Dose level	Animal	Effects noted after dosing (hours)				Effects noted during period after dosing (days)
(mg/kg)	No.	0,5	1	2	4	1	2	3	4	5	6	7	8	9	10	11	12	13	14
2000	Male 3-0	0	H	H	H	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	Male 3-1	0	H	H	H	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	Male 3-2	H	H	H	H	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	Male 3-3	0	H	H	H	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	Male 3-4	0	H	H	H	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	Female 4-0	H	H	H	H	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	Female 4-1	H	H	H	H	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	Female 4-2	0	H	H	H	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	Female 4-3	0	H	H	H	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	Female 4-4	0	H	H	H	0	0	0	0	0	0	0	0	0	0	0	0	0	0

0 = no signs of systemic toxicity

H = hunched posture

Applicant's summary and conclusion

Interpretation of results:

other: EU-GHS criteria not met

Conclusions:

Acute oral median lethal dose (LD50) of 2-pyrrolidone in the Sprague-Dawley CD strain rat was found to be greater than 2000 mg/kg bodyweight.

Executive summary:

The study was performed to assess the acute oral toxicicty of the test material in the Sprague-Dawley CD strain rat. The method of the study is according to the OECD Guideline 401 and is compliant to the GLP requirements.

A single oral dose of undiluted test material at dose level of 2000 mg/kg/bw was given to a group of ten fasted animals. The animals were observed within 14 days for signs of toxicity.

There were no deaths. Incidents of hunched posture were noted in all treated animals during the day of dosing. All animals appeared to be normal one to two days after treatment. No abnormalities were noted at necropsy.

The LD50 was found to be greater than 2000 mg/kg/bw.