Registration Dossier

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013
Report Date:
2013

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
traditional method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Details on test material:
- Identifier: CAS 80675-49-6
- Lot/batch No.: L-7015-20
- Yellow powder
- Storage conditions: Ambient temperature, no protection from light necessary
Specific details on test material used for the study:
- Identifier: CAS 80675-49-6
- Lot/batch No.: L-7015-20
- Analytical purity: 95%
- Yellow powder
- Storage conditions: Ambient temperature, no protection from light necessary

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories B.V., The Netherlands
- Age at study initiation: 9 weeks
- Weight at study initiation: ♂: 258.6 - 287.8 g, ♀: 172.3 - 195.3 g
- Fasting period before study: none
- Housing: Groups of 5 of the same sex
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 3 °C
- Humidity: 30 - 70 %
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 2013-01-03 To: 2013-01-24

Administration / exposure

Route of administration:
inhalation: dust
Type of inhalation exposure:
nose only
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Nose-only apparatus
- Method of holding animals in test chamber: restraint tubes
- Source and rate of air: The flow of air at each tube was 1.0 L/min, which is sufficient to minimize re-breathing of the test aerosol as it is more than twice the respiratory minute volume of rats.
- System of generating particulates/aerosols: CR3020 rotating brush aerosol generator connected to a micronizing jet mill.
- Method of particle size determination: The particle size distribution of the test aerosol was determined four times during exposure using a Mercer 7 stage cascade Impactor (Model 02-130, In-Tox. Products Inc., Albuquerque, New Mexico, U.S.A.). The particle size distribution was measured by gravimetrically analyzing the test item deposited on each stage of the cascade impactor.
- Temperature, humidity, pressure in air chamber: The oxygen concentration of the test atmosphere was measured continuously during exposure using a calibrated device. The results were recorded manually and are reported at 30 minute intervals from the start of exposure. The oxygen concentration was maintained above 19 % during exposure. The temperature and relative humidity of the test atmosphere was measured continuously during exposure using a calibrated device. The results were recorded manually and are reported in 30 minute intervals from the start of exposure. The actual airflow rate through the exposure chamber was recorded in approximately 30 minute intervals from the start of the inhalation exposure.

TEST ATMOSPHERE
- Brief description of analytical method used: The test item usage was measured by weighing the generator cylinders containing the test item before and after exposure to determine the quantity of test item used. The weight used was then divided by the total air-flow volume to give the nominal concentration.
- Samples taken from breathing zone: yes


TEST ATMOSPHERE: See tables 1 and 2

- Rationale for the selection of the starting concentration: The target concentration was considered to be the highest technically achievable concentration with a respirable particle size as determined in the technical trials. A target concentration of 2 mg/L air for 4 hours is the accepted concentration for a limit test (OECD 403, “Acute Inhalation Toxicity”) if a respirable particle size cannot be achieved at higher concentrations.
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
2.1 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: Body weights were recorded prior to exposure on test day 1, and during the observation period on test days 2, 4, 8, and 15 before necropsy. Regarding clinical signs, each animal was examined three times during exposure, immediately and 1 h after exposure on test day 1 and once daily during the observation period.
- Necropsy of survivors performed: yes

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 2.1 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Mortality:
None
Clinical signs:
other: Clinical signs were limited to the day of treatment and consisted of slightly ruffled fur in all animals and slight tachypnea in 3 males and 2 females. From test day 2 onwards, all animals were free from clinical signs.
Body weight:
Slight body weight loss was noted between test days 1 and 2 in all males and 4 females. In 3 of those females, this finding persisted up to test day 4. Thereafter normal body weight development was recorded.
Gross pathology:
There were no macroscopical findings at necropsy.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met