Registration Dossier

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
November 2, 2010 - July 28, 2011
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This study has been performed in accordance with OECD 403 (2009) and according to 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)
Version / remarks:
(2009)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: crystalline
Details on test material:
- Name of test material (as cited in study report): L579
- Physical description: white powder

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: SAGE LABS, Boyertown, PA, USA (received on January 18, 2011)
- Age at study initiation: 9 to 10 weeks
- Weight at study initiation: 272-293 g (males) and 188-210 g (females)
- Fasting period before study: no data
- Housing: singly housed in suspended stainless steel caging with mesh floors
- Diet: Purina Rodent Chow #5012
- Water: tap water (ad libitum, except during exposure)
- Acclimation period: 15 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-23 °C and 20-21 °C (during exposure)
- Humidity (%): 27-53% and 28-34% (during exposure)
- Air changes (per hr): 11 per hr
- Photoperiod (hrs dark / hrs light): 12 hrs dark / 12 hrs light

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: a nose-only inhalation chamber (ADG Developments Ltd.)
- Method of holding animals in test chamber: individually in polycarbonate holding tubes
- Source and rate of air: approximately 28.4 liters per minute of filtered air was supplied by an air compressor (Airgas) to the dust generator
- Method of conditioning air: an additional 3.3 liters per minute of compressed mixing air, supplied using air from a compressed air tank (Airgas), was introduced into the chamber, creating a vortex at the chamber inlet
- System of generating particulates/aerosols: the unground substance was aerosolized using a modified Wright Dust Generator driven by a variable speed motor (Dayton)
- Method of particle size determination: an eight-stage ACFM Westech Ambient Particle Sizing Sampler was used to assess the particle size distribution of the test atmosphere. Samples were withdrawn from the breathingzone of the animals at 2 intervals.
- Treatment of exhaust air: not applicable
- Temperature, humidity, pressure in air chamber: the exposure tube temperature and relative humidity ranges during exposure were 20 degrees Celsius and 33-36%, respectively

TEST ATMOSPHERE
- Samples taken from breathing zone: yes
- MMAD (Mass median aerodynamic diameter): 3.92 µm

CLASS METHOD
- Rationale for the selection of the starting concentration: not reported
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
5.09 mg/L (time weighted average)
No. of animals per sex per dose:
5
Control animals:
other: not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Body weights: prior to exposure and on days 1, 3, 7 and 14
Clinical signs: upon removal from the exposure tube and at least once daily thereafter
- Necropsy of survivors performed: yes

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5.09 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: Time weighted average chamber concentration; no mortalities occurred and no clinical signs were observed during the study
Mortality:
- There were no mortalities during the study
Clinical signs:
- There were no signs of treatment observed during the study
Body weight:
- No abnormalities were observed
Gross pathology:
- No abnormalities were observed

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In an acute inhalation study in rats, conducted in accordance with OECD 403 (2009) and according to GLP principles, rats (5 males and 5 females) were exposed by the nose only. The MMAD of the substance was determined to be 3.92 µm. No mortalities occurred during the study. There were also no signs of treatment observed during the study. Necropsy did not show any abnormality. Based on the results of this study, the 4h-LC50 was determined to be >5.09 mg/L and
the substance does not need to be classified for acute toxicity by the inhalation route.