Registration Dossier

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1991-07-08 to 1991-07-22
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Guideline study reliable without restrictions Minor deviations without an effect on the results: - No acclimatisation period was stated. - According to the guideline, an inhalation equipment to substain a dynamic air flow of 12 to 15 air changes per hour should be used. In this report it was only stated that the air flow was 1,500 l/h. - According to the guideline, the duration of the exposure should be at least 4 hours after equilibrium of the chamber concentration. In this study it was not stated, if exposure started after an equilibration period. -According to the guideline, the equipment for measuring temperature should be stated, which was not done in this study.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1992
Report Date:
1992

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
, see "rational for reliability"
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Physical state: Solid (powder) / yellow
- Storage condition of test material: Was stored at room temperature

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Dr. K. Thomae GmbH, D-W7950 Biberach, FRG)
- Age at study initiation: approx. 8-9 weeks
- Weight at study initiation: mean weight males: 305 +/- 2.8 g; mean weight females: 198 +/- 7.6 g
- Housing: Rats were housed singly in cages type DK III of becker, without bedding.
- Diet (ad libitum during the post exposure period): KIBA rat/mouse/hamster laboratory diet 24-343-4 10 mm pellets, Klingentalmühle AG, CH4303 Kaiseraugst, Switzerland
- Water (ad libitum during the post exposure period): drinking water

ENVIRONMENTAL CONDITIONS
- Temperature: 20 -24 °C
- Relative humidity: 30 - 70 %
- Photoperiod (hrs dark / hrs light): 12/12
No further information on the test animals was stated.

Administration / exposure

Route of administration:
inhalation: dust
Type of inhalation exposure:
nose/head only
Vehicle:
other: 1 wt% Aerosil
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Head-nose inhalation system INA 20 (glass-steel construction, BASF Aktiengesellschaft, volume V approx. 55 l): the animals were restrained in tubes and their snouts projected into the inhalation chamber.

- System of generating particulates/aerosols: The aerosol was produced with a dosing-wheel dust generator (Gericke/BASF) and compressed air. The concentration was adjusted by varying the rotation of the metering disc. An air flow rate (supply air) of 1,500 l/h was set.
By means of an exhaust air system the pressure ratios in the inhalation system were adjusted in such a way that the amount of exhaust air was about 10 % lower (excess pressure). This ensured that the mixture of test substance and air was not diluted with laboratory air in the breathing zones of the animals.

- Method of particle size determination: 30 minutes after the beginning of the test at the earliest, one sample was taken per test group for the particle size analysis.
Before the sampling, the impactor was equipped with glass-fiber collecting discs and a backup particle filter. The impactor was connected to the pump and the test apparatus, and one sample (9 l) was taken.
The impactor was taken apart, and the collecting discs and the backup particle filter were weighed.
The content of the pre-impactor as well as the amounts of the material adsorbed on the walls of the impactor and in the sampling probe (wall losses) were also determined quantitatively.
Equipment:
-Stack Sampler Mark III (Andersen)
- Vacuum Compressed Air Pump (Millipore)
-Sampling probe (internal diameter 6.9 mm)
- Balance: Sartorius M3P and Mettler AE 240
- Evaluation unit (IBM-PC with software PGA)

- Method of determination of the nominal concentration: The nominal concentration was calculated from the amount of substance consumed and the air flow.

- Temperature, humidity, pressure in air chamber: The humidity in the inhalation system was not measured due to technical reasons. It is assumed that deviations of humidity values from the guideline requirements (especially low humidity in dust aerosol) did not influence the test results, because of the relative short exposure time.
The temperature in the inhalation system was measured continuosly and recorded once.

TEST ATMOSPHERE
- Brief description of analytical method used: Gravimetric determination of the inhalation atmosphere concentration (Equipment: balance: Mettler AT 250). The preweighed filter was placed into the filtration equipment. By means of a vacuum compressed air pump a volume of the dust aerosol was drwan through the filter.
The dust concentration in mg/l was calculated from the difference between the preweight of the filter and the weight of the filter after sampling, with reference to the sample volume of the inhalation atmosphere.
Apparatus:
- Vacuum compressed air pump (Millipore)
- Filtration equipment with probe, internal diameter: 4 mm, (Millipore)
- Filter: MN 85/90 Bf (d = 4.7 cm)
- Sampling velocity: 1.25 m/s
- Sampling amount: 2 l
-Sampling frequency: 1 sample about hourly
- Samples taken from breathing zone: yes

VEHICLE
- Justification of choice of vehicle: The test substance was mixed with 1 wt % Aerosil in order to achieve a more uniform dus concentration in air.

TEST ATMOSPHERE
- MMAD/GSD: 2.7 µm (GSD: 3.9)
No further information on the inhalation exposure was stated.
Analytical verification of test atmosphere concentrations:
yes
Remarks:
see "details on inhalation exposure" above
Duration of exposure:
4 h
Concentrations:
Nominal concentration: 36.7 mg/l
Actual concentration: 5.5 +/- 0.82 mg/l
No. of animals per sex per dose:
5 males / 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The body weight of the animals was checked before the beginning of the test, after 7 days and at the end of the observation period. Clinical findings were recorded for each animal separately several times during the exposure and at least once each workday in the observation period. A check for dead animals was made daily.
- Necropsy of survivors performed: Yes
At the end of the 14-day observation period the animals were sacrificed with CO2 and were subjected to gross-pathological examination.
No further information on the study design was stated.
Statistics:
The statistical evaluation of the dose-response relationship was carried out using FORTRAN program AKPROZ. Depending on the data of the dose-response relationship obtained by way of experiment, this program is used to estimate the LC50 or to perform a Probit analysis (FINNEY, D.J. (1971): "Probit Analysis", Cambridge University Press). Estimation of the LC50 will produce types LC50 greater, LC50 about, or LC50 smaller. If the results are Type LC50 greater or LC50 smaller, an additional binominal test will be carried out (WITTING, H. (1974): "Mathematical Statistik" B.G. Teubner, Stuttgart, pp. 32 -35), in order to verify these statements statistically, if necessary.
The calculation of the particle size distribution was carried out in the Department of Toxicology of BASF Aktiengesellschaft on the basis of mathematical methods for evaluating particle measurements (DIN 66141: Darstellung von Korngrößenverteilungen, DIN 66151: Partikelgrößenanalyse (Beuth-Vertrieb GmbH, D-W1000 Berlin 30 and D-5000 Köln 1).

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5.5 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: The statistical reliability = 99 %.
Mortality:
No mortaility occurred at the limit concentration of 5.5 mg/l.
Clinical signs:
No abnormalities were detected in the animals of the test groups during exposure and post-exposure observation period. There was only a discolouration of the fur after termination of the exposure.
Body weight:
Body weight gain was influenced nor in male neither in female animals over the whole test period.
Gross pathology:
During necropsy no pathologic findings were noted.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
No mortality occured at the limit concentration of 5.5 mg/l. Therefore the LC50 is > 5.5 mg/l.
According to the criteria specified by Directive 67/548/EEC and subsequent regulations, the test item is not classified as acute toxic by the inhalation route.
According to the EC Regulation No. 1272/2008 and subsequent regulations, the test item is not classified as acute toxic by the inhalation route.