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Toxicological information

Acute Toxicity: inhalation

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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2013-01-17 to 2013-04-08
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 guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.2 (Acute Toxicity (Inhalation))
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
Harlan Laboratories Ltd, Toxicology and Environmental Safety & Metabolism, Zelgliweg 1, 4452 Itingen, Switzerland
Test type:
traditional method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Lot/batch No.of test material: COD-001701
- Expiration date of the lot/batch: 2014-11-01
- Purity test date: 2012-10-24


STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature (or cooler)

Test animals

Species:
rat
Strain:
Wistar
Remarks:
RccHanTM:WIST(SPF)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories B.V. Kreuzelweg 53 5961 NM Horst, Netherlands
- Age at study initiation: 8 weeks
- Weight at study initiation: Males: 263.2 to 280.4 g, Females: 177.8 to 193.8 g
- Fasting period before study: no
- Housing: Animals were housed in groups of 5 of the same sex in Makrolon® type-IV cages with wire mesh tops including paper enrichment and standard softwood bedding
- Diet: pelleted standard Harlan Teklad 2914C rat maintenance diet (ProvimiKliba AG, 4303 Kaiseraugst, Switzerland) ad libitum (except for period of restrainment in test tube)
- Water: community tap water from Füllinsdorf ad libitum (except for period of restrainment in test tube)
- Acclimation period: 6 days under optimal hygienic laboratory conditions. The animals were accustomed to the restraining tubes for 30 minutes on the day of exposure.

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

IN-LIFE DATES: From: 2013-01-22 To: 2013-02-11

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Remarks:
flow-past exposure
Vehicle:
not specified
Mass median aerodynamic diameter (MMAD):
>= 2.61 - <= 3.01 µm
Geometric standard deviation (GSD):
>= 2.36 - <= 2.82
Remark on MMAD/GSD:
Duration of sampling: 25 to 27 seconds per sample
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: flow-past, nose-only exposure system
- Method of holding animals in test chamber: restraining tubes
- Source and rate of air: The flow of air at each tube was 1.0 L/min
- Method of conditioning air:
- System of generating particulates/aerosols: A dust aerosol was generated from the test item using a 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 three times during exposure using a Mercer 7 stage cascade Impactor (Model 02-130, In-Tox. Products Inc., Albuquerque, New Mexico, U.S.A.).
- Temperature, humidity, pressure in air chamber: 22.8°C (mean), 5.5% RH (mean)

TEST ATMOSPHERE
- Brief description of analytical method used: Gravimetric analysis of Aerosol concentrations: The samples were collected on a Millipore®durapore filter, Type HVLP loaded in a 47 mm inline stainless steel filter sampling device. The filters were weighed before and immediately after sampling using a calibrated balance. The test aerosol concentration was calculated from the amount of test item present on the filter and the sample volume.
- Gravimetric aerosol concentration: 2.1 mg/L air (mean)

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: the particle size distributions obtained were considered to be respirable to rats and appropriate for acute inhalation toxicity testing.
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): 2.61 to 3.01 / 2.36 to 2.85
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
ca. 4 h
Concentrations:
2.4 mg/L air (mean chemical aerosol concentration)
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: 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.
- Frequency of weighing: The body weight of each animal was recorded on test days 1 (before exposure), 2, 4, 8 and 15 (before necropsy).
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
No statistical analysis was performed as only one group was allocated to the study.

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
discriminating conc.
Effect level:
> 2.4 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Mortality:
No mortality occured
Clinical signs:
other: Clinical signs were limited to the day of treatment and consisted of slight salivation during exposure and slightly ruffled fur immediately and one hour after exposure. Furthermore, tachypnea was noted in one male and three females during and shortly afte
Body weight:
Only marginal weight loss or stagnation was noted. This effect was considered to be mainly due to the restraining of the animals in the tubes.
Gross pathology:
There were no treatment-related macroscopic findings at necropsy.
Other findings:
- Histopathology: All collected organ and tissue samples were retained but neither processed nor examined.
- Potential target organs: not included
- Other observations: not included

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met