Registration Dossier

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
November 2, 2010 - June 7, 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): F10
- Physical description: white powder

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories, Indianapolis, IN, USA (received on April 26, 2011)
- Age at study initiation: 8 to 10 weeks
- Weight at study initiation: 215-256 g (males) and 158-195 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: 9 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-23 °C and 20-21 °C (during exposure)
- Humidity (%): 42-66% and 32-39% (during exposure)
- Air changes (per hr): 12-13 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 40 liters per minute of filtered air was supplied by an air compressor (Airgas) to the dust generator
- Method of conditioning air: an additional 65 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 Dust Generator with an accurate dry material feeder apparatus
- Method of particle size determination: an eight-stage ACFM Andersen 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 21-22 degrees Celsius and 34-41%, respectively

TEST ATMOSPHERE
- Samples taken from breathing zone: yes
- MMAD (Mass median aerodynamic diameter): 3.6 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
Mortality:
- There were no mortalities during the study
Clinical signs:
other: - Within 3 hours post-exposure, 2 males and 1 female exhibited irregular respiration, which was not observed the next day anymore - Within 1 day post-exposure, 1 male exhibited dry rales, which was not observed the next day anymore - Within 3 hours post-e
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 3.6 µm. All animals survived. Irregular respiration, dry rales and/or red facial staining was observed in 3 males and 2 females. By day 2 no treatment related effects were observed. Necropsy showed no abnormalities. 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.