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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:
03.11.1981 - 17.11.1981
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Comparable to Guideline 403. non GLP, but comparable reporting details

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1982
Report Date:
1982

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Physical state: solid, yellow
- Analytical purity: 88 %

- Stability: At least 2 years under normal conditions

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: WIGA Versuchstierzuchtanstalt, Sulzfeld, Germany, outbred strain: CAW-ICO-Wiga
- Age at study initiation: about 8 - 10 weeks
- Weight at study initiation: male animais 318 +/- 27 g, female animals 228 +/- 19 g
- Housing: five per cage, cages of Becker, type D III, without bedding.
- Diet: SSNIFF R complete diet for rats and mice, manufacturer: SSNIFF-Versuchstierdiaeten GmbH, Soest, Germany, ad libitum
- Water: tap water ad libitum during the observation period


ENVIRONMENTAL CONDITIONS
- Temperature (°C): temperature 22 +/- 2
- Humidity (%): 55 +/- 5
- Photoperiod (hrs dark / hrs light): 12 h/12 h

Administration / exposure

Route of administration:
inhalation: dust
Type of inhalation exposure:
nose/head only
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Read-nose inhalation system INA 20 (glass-steel construction, BASF AG)
- Exposure chamber volume: 55 L
- Method of holding animals in test chamber: The animals are restrained in tubes and their snouts project into the inhalation chamber.
- Source and rate of air: 1500 L/h compressed air by the injector and 1500 L/h ventilator air as dilution air.
- System of generating particulates/aerosols: A mixture of dust and air was generated by means of dust metering equipment (BASF).
By means of a dust generator the substance to be tested was generated into a dust aerosol, which was passed into the inhalation system.
An automatic vibrator was used for dust generation. The concentration was adjusted by varying the apertural width and varying the amplitude of oscillations of the metering beaker.
- Method of particle size determination: Andersen Stack Sampler Mark III Millipore vacuum compressed air pump XX 60 220 50, limiting orifice 3 L/min, Millipore sampling probe, internal diameter 6.9 mm, 30 minutes after the beginning of the test at the earliest, one sample was taken 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 removed.
The impactor was taken apart, and the collecting discs and the backup particle filter were weighed. The contents of the pre-impactor were determined gravimetrically.
- Pressure in air chamber: 1500 L/h compressed air by the injector and 1500 L/h ventilator air as dilution air
- To ensure, that the mixture of the test substance and air was not diluted with fresh air, the air suction system was reduced about 10 % compared to the supply air system (excess pressure).

TEST ATMOSPHERE
- Brief description of analytical method used:
• Vacuum compressed air pump (Millipore) XX 60 220 50,
• Filtration equipment with probe (Millipore) (internal diameter: 4 mm),
• Filter: MN 85/90 Bf (d = 4.7 cm),
• Balance: Cahn 26
Gravimetric determination of the concentration: the preweighed filter was placed into a filtration equipment. By means of a vaccuum compressed air pump a volume of the dust aerosol characterized by a limiting orifice was drawn 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.
- Samples taken from breathing zone: yes,
• Sampling: Velocity: 1.25 m/s, amount: 1 L, probe diameter: 4 mmm, frequency: half-hourly, in the immediate vicinity of the animal noses


- Particle size distribution: EACD 50% (effective aerodynamic cutoff diameter 50%);
Stage: Pre-impactor / EACD 50 % (µm): 26.6
Stage: Cascade impactor: Backup filter / EACD 50 % (µm): <1.2 / Percentage distribution (%): 41.14
Stage: Cascade impactor: 7 / EACD 50 % (µm): 1.2 / Percentage distribution (%): 18.69 / Cumulative distribution (%): 41.14
Stage: Cascade impactor: 5 / EACD 50 % (µm): 2.8 / Percentage distribution (%): 22.28 / Cumulative distribution (%): 59.83
Stage: Cascade impactor: 4 / EACD 50 % (µm): 5.5 / Percentage distribution (%): 8.40 / Cumulative distribution (%): 82.11
Stage: Cascade impactor: 3 / EACD 50 % (µm): 8.5 / Percentage distribution (%): 5.22 / Cumulative distribution (%): 90.51
Stage: Cascade impactor: 1 / EACD 50 % (µm): 18.2 / Percentage distribution (%): 2.14 / Cumulative distribution (%): 95.73
Stage: Cascade impactor: 0 / EACD 50 % (µm): 29.5 / Percentage distribution (%): 2.13 / Cumulative distribution (%): 97.87

A respirable dust fraction of 90.5% was obtained from the results of the particle size analysis.

- MMAD (Mass median aerodynamic diameter) 50 % = 1.7 µm/ GSD (Geometric st. dev.): 4.0
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
5.42 mg/l (analytical), 19.7 mg/l (nominal)
No. of animals per sex per dose:
5
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily observation, weighing; before start of application, then on day 7 and day 14,
- Necropsy of survivors performed: yes, with grosspathological examination.
- Other examinations performed: body weight
Statistics:
The statistical evaluation of the concentrations-response relationship was carried out in accordance with the binomial test (Wittig, H.: Mathematische Statistik 1974, pp.32 - 35) using tables of the BASF Computer Center.
The particle size was determined in accordance with mathematical and graphical methods of evaluating particle measurements (Silverman, L.: Particle Size Analysis in Industrial Hygiene, 1971, pp. 235-259).

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5.42 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: No mortality and no toxicity observed.
Mortality:
no mortality
Clinical signs:
During exposure: no abnormalities;
After exposure: fur discolored by the test substance, particularly the region of the head; otherwise no abnormalities.
Body weight:
The body weight of the animals showed no adverse effects in comparison with that of the control.
Mean body weight (male / female)
- Before the study
Treatment group: 318 / 228
Control: 307 / 230
- After 7 days
Treatment group: 345 / 242
Control: 340 / 240
- After 14 days
Treatment group: 368 / 251
Control: 367 / 249
Gross pathology:
No abnormalities detected.

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information