1,3-divinylimidazolidin-2-one

Endpoint summary

Description of key information

AOT: In the acute oral toxicity study the LD50 (rat) was determined to be 6,987 mg/kg bw.
AIT: In the acute inhalation toxicity study the LC50 (rat) was determined to be > 5.3 mg/L.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

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: Neither guideline nor GLP compliant study but nevertheless well documented and scientifically acceptable.

Principles of method if other than guideline:

according to BASF-internal standard

GLP compliance:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Mean weight for male animals about 190 g, for female animals about 177 g.
Diet: The rats received Altromin-R supplied by Altrogge, Lage/Lippe, Germany, and water ad libitum.

Route of administration:

oral: gavage

Vehicle:

other: 30% strength aqueous suspension (weight/vol.) with carboxymethyl cellulose and 2 - 3 drops of Cremophor EL

Details on oral exposure:

The test concentration used was 30%.

Doses:

3200, 4000, 5000, 6400, 8000 and 10000 mg/kg

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs

Sex:

male/female

Dose descriptor:

LD50

Effect level:

6 987 mg/kg bw

Based on:

test mat.

Mortality:

3200, 4000 and 5000 mg/kg: no deaths after 14 days
6400 mg/kg: 5/10 after 14 days
8000 mg/kg: 8/10 after 14 days
10000 mg/kg: 10/10 after 14 days

Clinical signs:

other: 6400 and 3200 mg/kg: immediately after administration lateral-abdominal position in some animals, apathy and atonia. Surviving animals normal after 4 days. 8000 and 10000 mg/kg: immediately after administration staggering, abdominal position, dyspnea, int

Gross pathology:

Animals that died: general congestion, acute cardiac dilatation, loam-colored liver.
Sacrificed animals: forestomach callously thickened with adhesions to peritoneum.

Interpretation of results:

not classified

Remarks:

Migrated information

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

6 987 mg/kg bw

Quality of whole database:

Neither guideline nor GLP compliant study but nevertheless well documented and scientifically acceptable.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

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.

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

no

GLP compliance:

no

Limit test:

yes

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

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.

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.

Interpretation of results:

not classified

Remarks:

Migrated information

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating conc.

Value:

5.3 mg/m³ air

Quality of whole database:

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

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Key study

 

Acute oral toxicity

BASF SE, study no.: XXIII/95, 1974

 

The acute oral toxicity of the test substance was determined in Sprague-Dawley rats. For this purpose, the product was administered once by gavage as a 30% aqueous suspension (weight/volume) with carboxymethyl cellulose and 2 - 3 drops of Cremophor EL at doses of 3,200 ; 4,000 ; 5,000 ; 6,400 ; 8,000 ; and 10,000 mg/kg .

The mean lethal dose (LD50) calculated according to FINNEY was 6,987 (6,327 - 7,716) mg/kg .

 

Key study

 

Acute inhalation study

BASF SE, study no.: 13I0403/887052, 1988

 

In an OECD 403 guideline compliant but not GLP compliant study the test substance was examined in rats at a concentration of 5.3 mg/L. 5 animals per sex were exposed to the test substance over a period time of 4 hours. No mortality was observed; therefore the LC50 was determined to be > 5.3 mg/L.

 

 

Justification for selection of acute toxicity – oral endpoint
Neither guideline nor GLP compliant study but nevertheless well documented and scientifically acceptable.

Justification for selection of acute toxicity – inhalation endpoint
Guideline compliant but not GLP compliant study but nevertheless well documented and scientifically acceptable.

Justification for classification or non-classification

Acute oral toxicity

 

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. As a result the substance is not considered to be classified for acute oral toxicity under Regulation (EC) No 1272/2008, as amended for the sixth time in Regulation (EC) No 605/2014.

 

 

Acute inhalation toxicity

 

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. As a result the substance is not considered to be classified for acute inhalation toxicity under Regulation (EC) No 1272/2008, as amended for the sixth time in Regulation (EC) No 605/2014.