1-methyl-2-pyrrolidone

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1988

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1988

Report date:

1988

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

concentration x time method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

1-methyl-2-pyrrolidone

EC Number:

212-828-1

EC Name:

1-methyl-2-pyrrolidone

Cas Number:

872-50-4

Molecular formula:

C5H9NO

IUPAC Name:

1-methylpyrrolidin-2-one

Test material form:

liquid

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: BASF AG

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: tightly closed container
- Stability under test conditions: guaranteed at least for the test period by the sponsor

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: no special pre-treatment performed

FORM AS APPLIED IN THE TEST: aerosol

Test animals

Species:

rat

Strain:

Wistar

Remarks:

SPF-Wistar/Chbb:THOM

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Dr. K. Thomae, 7950 Biberach, Germany
- Age at study initiation: about 8-9 weeks old
- Weight at study initiation: 282 g (males, mean value), 187 g (females, mean value)
- Housing: groups of 5 animals in type DIII cages (Becker, Germany) without bedding material
- Diet: conventional laboratory diet (Kliba laboratory diet rat/mice 24-343-4, 10 mm pellet, Klingenthalmuehle AG, Kaiseraugst, Switzerland), ad libitum
- Water: drinking water, ad libitum


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose/head only

Remarks:

System INA 20 (BASF AG, Germany)

Vehicle:

air

Mass median aerodynamic diameter (MMAD):

4.6 µm

Geometric standard deviation (GSD):

2.1

Remark on MMAD/GSD:

- Particle size distribution: 87 % capable of entering alveoli
- MMAD50% = 4.6μm (geometric standard deviation = 2 .1)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: INA 20 head-nose inhalation system
- Exposure chamber volume: 55 L
- Method of holding animals in test chamber: animals were placed in tubes with their snouts extending into the inhalation space
- Source and rate of air: compressed air, 1500 L/h
- System of generating particulates/aerosols: continuous infusion pump (INFU, Indigel, Switzerland) and a dual nozzle (model 970, Schlick)
- Method of particle size determination: gas chromatography
- Temperature in air chamber: 19 - 25 °C

TEST ATMOSPHERE
- Brief description of analytical method used: For a test group, a sample for particle size analysis was taken at the earliest 30 min after the beginning of the test. Before sampling, the impactor was fitted with metallic collection disks and a filter for residual particles. The impactor was connected to the pump and the test apparatus, and a sample (9 L) was taken. The impactor was taken apart. The collection disks and the residual particle filter were rinsed with 2-propanol. The samples thus obtained were analyzed by a gas-chromatographic method. The contents of the preimpactor and the amounts of material deposited on the impactor walls (wall losses) were also determined quantitatively.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

From the analytical data and the volume of the inhalation atmosphere sample, the concentrations were calculated in mg/L.

Duration of exposure:

4 h

Concentrations:

5.1 mg/L

No. of animals per sex per dose:

5 rats

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations were performed at least once per working day, weekly body weight determination.
- Necropsy of survivors performed: yes

Statistics:

Statistical evaluation of the dose-response relation was performed based on the binomial test (Wittig H, 1974. Mathematische Statistik, p. 32-35).
Particle size distribution was calculated based on mathematical evaluation methods for particle measurements (Silverman L, 1971. Particle size analysis in industrial hygiene, p. 235-259).

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5.1 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Mortality:

No mortality.

Clinical signs:

other: Accelerated, irregular breathing, slightly reddish nasal secretion and reduced pain sensitivity during exposure. Accelerated breathing, fur on head reddish coloured (blood test positive) and urine yellow coloured (metabolite effect) after exposure. There

Body weight:

Over the entire follow-up period, the body weight gain of the females in the test group remained unchanged relative to that in a historic control group. The body weight gain of the males in the test group relative to that in a historic control group was slightly retarded during the first follow-up week, but became normal during the second week.

Gross pathology:

Reddish-brown foci were noted in all lobes of the lungs (probably caused by aspiration).

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

There was no mortality observed and therefore the LC was >5.1 mg/L.
Apart from local effects, such as slightly reddish nasal secretion and reddish-brown foci in all lobes of the lungs no further effects were observed which were not reversible.

Executive summary:

The acute inhalation toxicity of NMP was investigated at a single concentration of 5.1 mg/L in a group of 5 male and 5 female Wistar rats following head-nose exposure for 4 hours of a vapour/aerosol mixture with a mass median aerodynamic diameter (MMAD) of 4.6 µm. The respirable fraction was 87 %. Observation period was 14 days. No animal died and all gained body weight. The LC50 was >5.1 mg/L after 4 hours. NMP is classified as being of low toxicity based on the LC50 in males and females.