Registration Dossier

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
23 July - 15 Oct 2004
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2004
Report Date:
2004

Materials and methods

Test guidelineopen allclose all
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Qualifier:
according to
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries (MAFF), Testing Guidelines for Toxicology Studies, 12 NohSan No. 8147 (2-1-3)
Version / remarks:
partially revised on 26 July 2001
GLP compliance:
yes (incl. certificate)
Remarks:
THE DEPARTMENT OF HEALTH OF THE GOVERNMENT OF THE UNITED KINGDOM, UK
Test type:
traditional method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder

Test animals

Species:
rat
Strain:
other: Crl:CD (SD) IGS BR
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Ltd, Margate, UK
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: approximately 8 - 12 weeks
- Weight at study initiation: 200 - 350g
- Housing: in groups of five per sex in solid-floor polypropylene cages with stainless steel lids on softwood flakes, environmental enrichment items (wooden chew blocks and cardboard “fun tunnels”) were provided
- Diet: EU Rodent Diet 5LF2 (BCM IPS Limited, London, UK), ad libitum (with the exception of the exposure period)
- Water: mains drinking water, ad libitum (with the exception of the exposure period)
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 2
- Humidity (%): 55 ± 15
- Air changes (per hr): at least 15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
inhalation: dust
Type of inhalation exposure:
nose only
Vehicle:
air
Mass median aerodynamic diameter (MMAD):
4.84 µm
Geometric standard deviation (GSD):
2.77
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: cylindrical exposure chamber (28 cm diameter x 50 cm high)
- Exposure chamber volume: 30 L
- Method of holding animals in test chamber: Each rat was individually held in a tapered, polycarbonate restraining tube fitted onto a single tier of the exposure chamber and sealed by means of a rubber ‘O’ ring. Only the nose of each animal was exposed to the test atmosphere.
- Source and rate of air: Compressed air was supplied by means of an oil free compressor and passed through a water trap and respiratory quality filters before it was introduced to the dust feeder.
- System of generating particulates/aerosols: A dust atmosphere was produced from the test material using a Wrights Dust Feeder (BGI Inc., Waltham, USA) located at the top of the exposure chamber and driven by a variable speed motor. The dust feed was connected to a metered compressed air supply. A particle separator was introduced before the aerosol entered the exposure chamber in order to remove large particles and thereby increase the inhalable por ion of the generated aerosol.
- Method of particle size determination: The particle size of the generated atmosphere inside the exposure chamber was determined 3 times during the exposure period using a Marple Personal Cascade Impactor (Schaefer Instruments Ltd, Oxon, UK).
- Treatment of exhaust air: The extract from the exposure chamber passed through a scrubber trap and was connected with a high efficiency filter to a metered exhaust system.
- Temperature, humidity, pressure in air chamber: The temperature and relative humidity inside the exposure chamber were measured by an electronic thermometer/humidity meter (Hanna Instruments Ltd, Beds, UK) located in a vacant port in the animals' breathing zone of the chamber and recorded every 15 min throughout the 4-h exposure period. Temperature was 19 °C and relative humidity 38 - 59%. The chamber was maintained under negative pressure.


TEST ATMOSPHERE
- Brief description of analytical method used: The actual chamber concentration was measured at regular intervals during the exposure period. The gravimetric method used glass fibre filters (Gelman type A/E 25 mm) placed in a filter holder. The holder was temporarily sealed in a vacant port in the exposure chamber in the animals' breathing zone and a suitable, known volume of exposure chamber air was drawn through the filter using a vacuum pump.
- Samples taken from breathing zone: yes
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
1.34 ± 0.64 mg/L (maximum attainable concentration)
25.2 mg/L (nominal 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 and weighing: All animals were observed for clinical signs at hourly intervals during exposure, immediately on removal from the restraining tubes at the end of exposure, 1 hour after termination of exposure and subsequently once daily for 14 days. Individual body weights were recorded prior to treatment on the day of exposure and on Days 7 and 14.
- Necropsy of survivors performed: yes

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 1.34 mg/L air (analytical)
Based on:
test mat.
Remarks:
maximum attainable concentration
Exp. duration:
4 h
Mortality:
No mortality occurred during the study period.
Clinical signs:
other: Signs of hunched posture and pilo-erection are commonly seen in animals for short periods on removal from the chamber following 4-hour inhalation studies. Wet fur is commonly recorded both during and for a short period after exposure. These observations a
Body weight:
All animals gained the expected body weight over the study period.
Gross pathology:
No abnormalities were noted at necropsy.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
In this acute inhalation toxicity study a LC50 of greater than 1.34 mg/L air in male and female rats was found. This concentration was the maximum attainable concentration.