Registration Dossier

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
June 8 to July 1, 2011
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study performed according to current OECD test guidelines and GLP principles.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2011
Report Date:
2011

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): E-Y110
- Physical state: Orange powder (Solid)
- Lot/batch No.: MB-1
- Expiration date of the lot/batch: May 31, 2016
- Storage condition of test material: Room temperature, dark place

Test animals

Species:
rat
Strain:
other: Crl:CD(SD)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories Japan, Inc.
- Age at study initiation: 8 weeks
- Weight at study initiation: 274-305 g for males, 195-206 g for females
- Fasting period before study: From the evening on the day before the administration (approx 18 hours predose) to about 3 hours postdose.
- Housing: Polycarbonate cages (W265xD426xH200 mm), stainless steel racks and feeders, autoclaved bedding was used, two animals per cage (same sex)
- Diet (ad libitum): Pellet diet (MF, Oriental Yeast Co., Ltd.) (each lot analysed: contaminants confirmed to be within acceptable limits of test facility)
- Water (ad libitum): Tap water filtered through a 5 microm filter and irradiated by UV light (analysed every 6 months: contaminants confirmed to be within acceptable limits of the test facility)
- Acclimation period: at least 5 days,

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.9-22.4
- Humidity (%): 47.8-58.9
- Air changes (per hr): 6 to 20
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
inhalation: dust
Type of inhalation exposure:
nose only
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: A flow-past nose-only inhalation exposure chamber.
- Exposure chamber volume: not reported
- Method of holding animals in test chamber: Animals were restrained in restraining tubes for nose-only inhalation exposure. The chamber has 16 exposure ports per tier, and a one tier chamber was used.
- Source and rate of air: The flow rate air supply was 16 L/min. A fluidized-bed dust generator was used to generate dust.
- Method of particle size determination: Test atmosphere collected in 8 stages using a cascade impactor at 1 and 3 hr after the start of the exposure. A glass fiber filter was used as the collection substrate. Air flow ratio for the collection was set at 500 ml/min, duration was set at 1.5 min. Glass fibers were weighed before and after collection, the test substance weights in each stage being the weight difference. The particle size distribution was calculated with the effective cut-off diameter of each stage of the cascade impactor and the amount collected in each stage. The following parameters were calculated: MMAD, GSD, weight ratio of particles with <4µm to total particles.
- Temperature, humidity, pressure in air chamber: Pressure of chamber positive. Temperature and relative humidity measured at exposure port with digital thermo-hygrometer: Temperature: 23.0°C and humidity: 49-52% throughout exposure.

TEST ATMOSPHERE
- Brief description of analytical method used: The measurement of the exposure concentration before the start of exposure was conducted after a particle count concentration (relative concentration), which was measured at the exposure port, reached equilibrium. The nominal concentration was 5 mg/l, the mean actual exposure concentration is 2.3 mg/l.

VEHICLE
no

TEST ATMOSPHERE
- Particle size distribution: At 1 and 3 hrs after the start of the exposure, MMAD of the dust measured was 4.8 and 5.3 µm and GSD at each measuring oint was 1.9 and 1.9,. respectively. The ratio of the particles with a diameter less than 4 µm, considered to be the inhalable particle size for rats, were 39.0 and 32.9%, respectively.
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): 4.8 and 5.3 µm / 1.9 µm

CLASS METHOD
- Rationale for the selection of the starting concentration: The exposure concentration was set at 2 mg/L which is permissible concentration as maximum concentration according to the applied guideline. Since the MMAD of the dust obtained in the preliminary dust generation trial was larger than the recommended range in the guideline, the target concentration was set at 2 mg/L to achieve the particle size of the recommended range.
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
2.3 mg/l
No. of animals per sex per dose:
6
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Mortality and clinical signs were observed immediately after the end of exposure (on Day 1, day of exposure), 1, 2 hours postdose on Day 1 and once daily for 14 days thereafter. Body weight was measured just before the administration (Day 1) and on Days 2, 4, 8, and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: none
Statistics:
none required.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 2.3 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: exposure to dust
Mortality:
No animals died.
Clinical signs:
Soiled fur on the whole body drived from the test substance was observed in males and females immediately after exposure, which disappeared on day 2. Soiled fur on the head and face was observed in males and females on day 2.
Body weight:
Body weight losses or depression of body weight gain was noted in males and females on day 2. Their body weight increased in all males on day 8 and in females on day 4.
Gross pathology:
There were no abnormalities in any males or females.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The LC50 of E-Y110 was determined to be more than 2.3 mg/L (dust) under the conditions of this study (OECD 403).
Executive summary:

A single exposure to 2.3 mg/L dust of E-Y110 (nose only) was conducted to male and female SD (Crl:CD(SD)) rats aged 8 weeks to evaluate its acute inhalation toxicity in accordance with the OECD test guideline 403. The MMAD of the dust was 4.8 and 5.3 µm at 1 and 3 hours, respectively, after start of exposure. The ratios of particles with a diameter < 4 µm, were 39.0% and 32.9% at 1 and 3 hours, respectivelty, after start of exposure. As a result, there were no deaths, or necropsy findings. Decreases in body weight or suppression of body weight gain were noted in males and females on days 2 and 4. In addition, soiled fur was noted on day 1 and 2. In conclusion, the LC50 of E-Y110 was determined to be more than 2.3 mg/L under the conditions of this study.