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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:
2005-03-16 to 2005-10-04
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2005
Report Date:
2005

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
Remarks:
Some minor deviations which do not influence integrity and validity of the study and its results.
Qualifier:
according to
Guideline:
EU Method B.2 (Acute Toxicity (Inhalation))
Deviations:
no
Remarks:
Some minor deviations which do not influence integrity and validity of the study and its results.
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River, Sulzfeld, Germany
- Age at study initiation: 10 - 11 weeks
- Weight at study initiation: mean males 303 g, mean females 194 g
- Fasting period before study: none
- Housing: Macrolon cages with a stainless steel wire lid and wood shavings (Espen E-00 1; ABEDD, Köflach, Austria) as bedding material. The animals were housed five males or five females to a cage.
- Diet (e.g. ad libitum): ad libitum except during exposure (no access to food)
- Water (e.g. ad libitum): ad libitum except during exposure (no access to water)
- Acclimation period:5 weeks

ENVIRONMENTAL CONDITIONS
According to guideline

IN-LIFE DATES: From: 2005-05-18 To:2005-07-05

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
clean air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: ADG Developments Ltd., Codicote, Hitchin, Herts, SG4 8UB, UK
- Exposure chamber volume: 50 l
- Method of holding animals in test chamber: The animals were secured in plastic animal holders (Battelle ), positioned radially through the outer cylinder around the central column.
- Source and rate of air: Fresh, cleaned ambient air. 90.45 L/min.
- Method of conditioning air: The test atmosphere was generated by passing the milled test material to an eductor (Fox mini type 060, Fox Valve Development corp., Dover, NJ, USA) using a dry material feeder (Gericke GMD 60, Gericke AG, Regensburg, Switzerland). The eductor was placed at the top inlet of the exposure unit and was operated with humidified compressed air controlled by a pressure reducing valve at a constant pressure of 1.0 bar.
- System of generating particulates/aerosols: The milled test material was delivered in a slip stream of humidified ambient air.
- Method of particle size determination: Particle size distribution measurements were carried out once during preliminary testing and once during exposure using a 10-stage cascade impactor (Andersen, Atlanta, USA). The Mass Median Aerodynamic Diameter (MMAD) and the geometric standard deviation (gsd) were calculated.
- Treatment of exhaust air: The test atrmosphere was exhausted at the bottom of the test unit
- Temperature, humidity, pressure in air chamber: The mean temperature during exposure was 21.8 ± 0.2°C and the mean relative humidity was 49 ± 1% (range 48 - 50%). The oxygen concentration in the inhalation unit during exposure was 20.9%. The mean air flow through the exposure unit was 90.45 Llmin.

TEST ATMOSPHERE
- Brief description of analytical method used:
Gravimetric analysis six times during exposure. The test atmosphere was sampled in the breathing zone of the animals. Representative test atmosphere samples were obtained by passing measured amounts of test atmosphere at a sampling flow of 5 L/min through glass fibre which weere weighed before sampling and after loading.
- Samples taken from breathing zone: yes

VEHICLE
- Composition of vehicle (if applicable): clean air
- Concentration of test material in vehicle (if applicable): 5 g/m³
- Justification of choice of vehicle: normal brating conditions


TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: 1 - 4µm
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): During exposure, about 87% of the mass of the aerosol present at the animals' breathing zone was contained in particles with an aerodynamic diameter equal to or smaller than 7.5 µm. The MMAD during exposure was estimated tobe 3.8 µm. The distribution of particle sizes had an estimated gsd of 2.1.

Analytical verification of test atmosphere concentrations:
yes
Remarks:
Determined by gravimetric analysis 6 times during exposure
Duration of exposure:
4 h
Concentrations:
5.26 g/m³
No. of animals per sex per dose:
5 male, 5 female
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: At least once a day
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs just before exposure, shortly after exposire and at least daily during the 14-day observation period. Body weight just before exposure and on day 7 as well as day 14. Gross pathological changes with particuliar reference to any changes in the respiratory tract.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5 260 mg/m³ air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Mortality:
No mortality
Clinical signs:
other: Slightly decreased breathing rate was observed in all animals throughout the entire exposure period. An hour after exposure, slight irregular breathing and slight or moderate blepharospasm were observed in all animals, accompanied in one male (animal no.
Body weight:
Overall body weight gain in male and female animals was observed.
Mean values for males:
Day 0 302.8 g (sd 8.3. g), day 7 317.5 g (sd 7.8 g), day 14 336.4g (sd 12.1 g)
Mean values for female:
Day 0 193.5 g (sd 4.8 g), day 7 200.2 g (sd 6.3 g), day 14 207.0 g (sd 6.6 g)
Gross pathology:
Macroscopic examination at necropsy did not reveal treatment-related gross changes.
Other findings:
A sparsely haired skin was seen in one female, but this finding was not considered to be related to treatment.

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: OECD GHS
Conclusions:
The 4-h LC50 value of L-valine in rats was > 5.26 g/m³ for both sexes.