1,3-divinylimidazolidin-2-one

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Guideline compliant but not GLP compliant study but nevertheless well documented and scientifically acceptable.

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:

no

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

1,3-divinylimidazolidin-2-one

EC Number:

237-457-2

EC Name:

1,3-divinylimidazolidin-2-one

Cas Number:

13811-50-2

Molecular formula:

C7H10N2O

IUPAC Name:

1,3-diethenylimidazolidin-2-one

Details on test material:

Name of the test substance used in the study report: Divinyl ethylene urea
Purity: > 99.5%

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: breeding facility : Dr . K . Thomae GmbH, D-W7950 Biberach, Germany
- Age at study initiation: 8 - 9 weeks
- Weight at study initiation: male animals 275 ± 10.1 g, female animals 19.4 ± 6.8 g
- Housing: Groups of five in cages type DK III of Becker, without bedding, with a light/dark rhythm of 12 hours
- Diet: The animals were offered KLIBA rat/mouse laboratory diet, ad libitum
- Water: Drinking water ad libitum, during the post-exposure observation period


ENVIRONMENTAL CONDITIONS
- Temperature: 20-24°C
- Humidity: 30-70%
- Air changes: Fully air-conditioned rooms, range were regulated by means of a central air-conditioning system

Administration / exposure

Route of administration:

other: inhalation: dust aerosol

Type of inhalation exposure:

nose/head only

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: A dust aerosol was generated by means of a dosing-wheel dust generator (Gericke/BASF). The substance to be tested was ground and mixed with 1.5 weight% aerosil to obtain a more homogeneous distribution of dust in air. Concentration adjustmust was achieved by variable rotation of the dosing wheel.
- Exposure chamber volume: Head-nose inhalation system INA 20 (glass-steel construction, BASF Aktiengesellschaft, volume V = 55 L)
- Method of holding animals in test chamber: The animals were restrained in tubes and their snouts projected into the inhalation chamber.
- Source and rate of air: The following air volume (stream of supply air) was adjusted: Compressed air: 1,500 L/h
- Method of particle size determination: Impactor method ( Stack Sampler Mark III)
- Treatment of exhaust air: By means of an exhaust air system the pressure ratios in the inhalation system were adjusted in such a way that the amount of exhaust air was about 10% lower (excess pressure). This ensured that the mixture of test substance and air was not diluted with laboratory air in the breathing zones of the animals.
- Temperature, humidity, pressure in air chamber: 19-25°C; Due to appropriate measures, the supply air adjusted itself to the same temperature that was found in the centrally air-conditioned laboratories.

TEST ATMOSPHERE
- Brief description of analytical method used: Gravimetric determination of the inhalation atmosphere concentration (Sampling amount: 2 L)
The preweighed filter was placed into the filtration equipment. By means of a vacuum compressed air pump a volume of the dust aerosol was drawn through the filter .
The dust concentration in mg/L was calculated from the difference between the preweight of the filter and the weight of the filter after sampling, with reference to the sample volume of the inhalation atmosphere. The concentrations were corrected for the amount of the added excipient.
- Samples taken from breathing zone: yes


TEST ATMOSPHERE
- Particle size distribution: Calculated on the basis of mathematical methods of evaluation for particle measurements (DIN 66 141, Representation of particle size distribution, DIN 66 161 : Particle size analysis)
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): 50% = 4.9 µm; GSD = 2.5

CLASS METHOD
- Rationale for the selection of the starting concentration: Based on guideline

Analytical verification of test atmosphere concentrations:

yes

Remarks:

Gravimetric determination of the inhalation atmosphere concentration

Duration of exposure:

4 h

Concentrations:

5.3 mg/L

No. of animals per sex per dose:

5

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The body weight of the animals was checked before the beginning of the test, after 7 days and at the end of the observation period. Clinical findings were recorded several times during exposure and at least once on each workday in the observation period. A check for dead animals was made daily.
- Necropsy of survivors performed: Yes, at the end of the 14-day observation period the animals were sacrificed with C02 and were subjected to gross-pathological examination
- Other examinations performed: clinical signs, body weight

Statistics:

The statistical evaluation of the concentration-response relationship was based on the binominal test.
The particle size distribution was calculated on the basis of mathematical methods of evaluation for particle measurements.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5.3 mg/L air

Based on:

test mat.

95% CL:

> 99.9

Exp. duration:

4 h

Mortality:

none

Clinical signs:

other: During exposure: Accelerated breathing; reddish nasal discharge After exposure: Accelerated breathing; general state of health slightly deteriorated; piloerection; fur around snout with reddish smear (blood test positive). The animals of the concentration

Body weight:

Compared to the historical control, the body weight change of the male and female animals of the test group was slightly retarded during the first week of observation, but became normal during the second week of observation.

Gross pathology:

Sacrificed animals (male and female animals): Nothing abnormal found in the organs.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information