Registration Dossier

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
aug-oct, 2011
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study has been performed according to OECD guidelines and according to GLP principles.

Data source

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

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
other: MAFF in Japan (12-Nousan-No. 8147, 2-1-3, 2000)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): E-BW102
- Physical state: red-brown powder

- Storage condition of test material: under dark condition at room temperature (actual range 20.7-22.3°C)

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source:Tsukuba Breeding Center (Ibaraki, Japan) of Charles River Japan, Inc.
- Age at study initiation: 8 weeks
- Weight at study initiation: 288-309 grams (males); 208-229 grams (females)
- Fasting period before study: not indicated
- Housing: wire-mesh stainless steel cage; during quarantine and acclimatization period, 5 or 2 animals of the same sex were housed in a cage. After selection of animals, 5 animals of the same sex were housed in a cage.
- Diet: pellet diet MF (Oriental Yeast Co., Ltd., Tokyo, Japan); ad libitum
- Water: local tap water; ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23±2°C
- Humidity (%): 60±20
- Air changes (per hr): 8
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: August 19, 2011 To: September 2, 2011

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
Animals were individually held in animal holders attached to a snout-only exposure chamber (total volume 31.2 L). The dust was generated by a turn-table type dust feeder with compressed air. The compressed air was supplied to the dust feeder through an air filter. Airflow to the chamber was controlled by an ejector in the dust feeder at a rate of 20 L/min. The chamber air was exhausted through an air filter system consisting of a bag filter, a HEPA filter and an activated charcoal filter. The differential pressure in the chamber was adjusted to and maintained between -20 and -5 mm H2O using exhaust-adjusting valve. Aiflow rate in the dust feeder was continuously confirmed and recorded every 30 minutes during the exposure period.

Nominal concentration: the total amount of active ingredient of the test substance supplied to the chamber was determined gravimetrically with adjustment for the purity. The nominal concentration (mg/L) was calculated by dividing the total amount of active ingredient (mg) by total air volume (L) deliverd during exposure.
Actual concentration: the actual concentration was quantified at 1, 2 and 3 hours after the initiation of exposure. Six litters of chamber air was drawn from the chamber sampling port. The test substance dust was trapped on a pre-weighed glass fiber filter and the amount of the test substance trapped was determined gravimetrically using an electronic balance. The actual concentration (mg/L) was calculated by dividing the amount of the active ingredient (mg) with adjustment for the purity trapped on a glass fiber filter by air volume (L) sampled.

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution (MMAD): 4.96 µm (4.77-5.12 µm)
- GSD (Geometric st. dev.): 2.20 (2.07-2.30)
- Mean volume of actual concentration = >5.01 mg/L (>4.80->5.40)
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
5 mg/L
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: observations for mortality and clinical signs at 2 hours after initiation of exposure, immediately, 1 and 4 hours after the exposure, and once daily thereafter until termination of the observation period. Each animal was weighed shortely before the exposure on the day of treatment and when found dead, on 1, 3, 7 and 14 days after exposure.
- Necropsy of survivors performed: yes
- Other examinations performed: none
Statistics:
The range of LC50 value was determined from the mortality.

Results and discussion

Preliminary study:
A dose-finding acute inhalation toxicity study with 1.0 and 5.0 mg/L E-BW102 was performed with 5 rats/sex (study no IET 11-0057). No mortality was observed during the 7-day observation period. Based on these results, a limit test at 5 mg/L was considered for the main study.
Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Mortality:
none
Clinical signs:
other: none
Body weight:
Body weight losses were observed in all animals on day 1 after exposure, and in 1 male on 3 days after exposure (as compared with body weight before exposure). All animals gained weight on days 7 and 14 after exposure.
Gross pathology:
no macroscopic abnormalities were noted
Other findings:
no

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
No mortality was observed after 4h snout-only exposure to E-BW102. Based on these results, the LC50 value of E-BW102 for both sexes of rats in this study was more than 5 mg/L, and E-BW102 needs not to be classified for acute inhalation toxicity according to GHS.
Executive summary:

The acute inhalation toxicity of E-BW102 was tested in Sprague-Dawley rats. Animals (5/, 5f) were exposed for 4 hours in a snout-only exposure chamber to 5 mg/L E-BW102. MMAD and GSD were 4.96 µm and 2.20, respectively. No mortality and no clinical signs were observed during the 14 day observation period. Body weights were reduced in all animals on day 1 after exposure (and on day 3 in 1 male), but all animals gained weight on days 7 and 14 after exposure. No macroscopic abnormalities were noted at the end of the observation period. Based on these results, the LC50 of E-BW102 for both sexes of Sprague-Dawley rats in this study was more than 5 mg/L.