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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
3 October 1983 to 17 October 1983
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1987
Report date:
1987

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Version / remarks:
1981
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
GLP statement dates to Dec 18, 1987 QA statement dates to Nov 21, 1983
Test type:
traditional method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
1-(3,5-dichloro-2,4-difluorophenyl)-3-(2,6-difluorobenzoyl)urea
EC Number:
617-441-5
Cas Number:
83121-18-0
Molecular formula:
C14 H6 Cl2 F4 N2 O2
IUPAC Name:
1-(3,5-dichloro-2,4-difluorophenyl)-3-(2,6-difluorobenzoyl)urea
Test material form:
solid

Test animals

Species:
rat
Strain:
other: KFM: Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Kleintierfarm Madoerin AG, CH 4414 Fuellinsdorf/Switzerland
- Age at study initiation: males: 7 weeks, females: 9 weeks
- Weight at study initiation: males: 220 - 293 g, females: 191 - 206 g
- Fasting period before study: No
- Housing: The animals were caged in groups of 5 in Makrolon type-4 cages with wire mesh lids
- Diet: ad libitum (with the exception of the exposure period), pelleted standard Kliba 343, rat maintenance diet (Klingentalmuehle AG, CH 4303 Kaiseraugst /Switzerland)
- Water: ad libitum (with the exception of the exposure period), tap water
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 45-65
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
inhalation: dust
Type of inhalation exposure:
nose only
Vehicle:
air
Remark on MMAD/GSD:
Particle size was measured twice 1 and 3 hours after exposure start. Approximately 38 % of the determined particles were within a size range of 1 to 7 microns.
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: the exposure chamber (H. Born & Co., Mechan. Werkstatt, CH 4313 Moehlin / Switzerland).
- Exposure chamber volume: 100 L
- Method of holding animals in test chamber: the rats were placed around the exposure chamber in separate radial polyvinylchloride tubes with their snouts and nostrils exposed to the aerosol only.
- System of generating particulates/aerosols: the test substance was supplied to the nozzle by a Grafix Exaktomat injector (Cerutti AG, Bern / Switzerland). The air flow was 1000 L/hr and air pressure was 3 atmospheres. The spray nozzle discharged into the air of the chamber.
- Method of particle size determination: Gravimetrical determination with the aid of a 4 stage cascade impactor (Casella Ltd., London/England) on selectron filters, pore size 0.2 µm and 25 mm in diameter (Schleicher and Schuell, Feldbach/Switzerland). The particle size distribution shows for each filter of the cascade impactor the portion in % of the weight of particle sediment.
- Temperature, humidity, pressure in air chamber:
Oxygen content in chamber air: A constant amount of 20 vol. % of oxygen was found to be inside the exposure chamber during the test period (measured with OXYCOM 25 D, Draegerwerk AG, Zurich/Switzerland).
Relative humidity of chamber air: The relative humidity of the chamber air varied between 26 and 32 % during the exposure period (measured with HM 14, VAISALA humidity indicator, Kuenzli Elektronik, Zurich/Switzerland)
Chamber temperature: The chamber temperature was found to be within 22.9 and 23.4°C during the exposure period (measured with Therm 3420, contact thermometer, Interstar AB, Zug/Switzerland)

TEST ATMOSPHERE
- Brief description of analytical method and equipment used:
Determination of exposure concentration: Gravimetrical determinations on selectron filters, pore size 0,2 µm and 50 mm in diameter (Schleicher and
Schuell, Feldbach/Switzerland). Air flow: 10 l/min., equal 1.25 meters/sec.
Aerosol particle size determination: Gravimetrical determination with the aid of a 4 stage cascade impactor (Casella Ltd., London/England) on selectron filters, pore size 0.2 µm and 25 mm in diameter (Schleicher and Schuell, Feldbach/Switzerland). Air flow: 17.5 L/min. (which is usually used) gives velocities through the 4 jets of 2.2, 10.2, 27.5, and 77 m/s, respectively.
The particle size distribution shows for each filter of the cascade impactor the portion in % of the weight of particle sediment.London/England)
- Samples taken from breathing zone: yes

Analytical verification of test atmosphere concentrations:
yes
Remarks:
measured 5 times during exposure.
Duration of exposure:
4 h
Concentrations:
nominal concentration: 33 g/m³ air
measured concentration: 5.048 g/m³ air
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Mortality: 5 times during the first day and daily thereafter
Symptoms: 5 times during the first day and daily thereafter
Body weights: At days 1 (day of exposure), 8 and 15 of test
- Necropsy of survivors performed: yes
- Other examinations performed: concentration (5 times during exposure), particle size (twice during exposure), oxygen content, humidity and temperature (8 times during exposure)
Statistics:
The LOGIT-Model could not be applied to the observed rates of death. The LC50 was estimated without use of a statistical model.

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5 038 mg/m³ air
Based on:
test mat.
Exp. duration:
4 h
Mortality:
No mortality occurred.
Clinical signs:
other: Dyspnea and ruffled fur was observed in all rats, starting within 2 hours of exposure. All rats recovered within 2 days after starting the exposure.
Body weight:
The body weight gain was unaffected by the exposure procedure.
Gross pathology:
No pathologic changes were observed during the macroscopic examination of all animals.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met