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Toxicological information

Acute Toxicity: oral

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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).
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1999
Report Date:
1999

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
1) No 95%-CI for LD50; 2) No dose-mortality curve and slope
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes (incl. certificate)
Remarks:
The Departament of health of the Goverment of the UK
Test type:
fixed dose procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
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 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:
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")
Body weight:
Expected gain in bodyweight observed in all animals during the stuy.
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

10 

11 

12 

13 

14 

2000

Male 3-0 

0

H

H

H

Male 3-1 

H

H

H

Male 3-2 

H

H

H

H

0

Male 3-3 

0

H

H

H

Male 3-4 

H

H

H

0

 0

0

Female 4-0 

H

H

H

H

Female 4-1

H

H

H

H

Female 4-2

H

H

H

0

Female 4-3 

0

H

H

H

Female 4-4

H

H

H

0

 0

0

0 = no signs of systemic toxicity

H = hunched posture

Applicant's summary and conclusion

Interpretation of results:
other: no symbol and risk phrase required
Remarks:
Criteria used for interpretation of results: other: EC labelling regulations
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.