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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:
13.10.1982 - 27.10.1982
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1983
Report Date:
1983

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
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

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: THOM; Zuchtbetrieb: Dr. K. Thomae GmbH, 7950 Biberach
- Age at study initiation: 8 weeks
- Weight at study initiation: 245 g (males) and 179 g (females)
- Housing: type DIII (Fa. Becker)
- Diet: SSNIFF R 10 mm Pellet, Ssniff-Versuchstierdiäten GmbH, 4770 Soest, ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20- 24
- Humidity (%): 30 - 70
- Air changes (per hr): Fully airconditioned room
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Route of administration:
inhalation: dust
Type of inhalation exposure:
nose/head only
Vehicle:
clean air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Head-nose inhalation system INA 20 (glass-steel construction, BASF Aktiengesellschaft)
- Exposure chamber volume: ca. 55 L
- Method of holding animals in test chamber: the animals were restrained in tubes and their snouts projected into the inhalation chamber
- Source and rate of air: 1500 L/h, supply air
- Method of conditioning air: The exposure system was placed in an air-conditioned laboratory. Temperatures in the exposure system were 19-25 °C
- System of generating particulates/aerosols: A dust aerosol air mixture was generated by means of a dust generator.
- Method of particle size determination: Stack Sampler Mark III (Andersen)

TEST ATMOSPHERE
- Brief description of analytical method used: The preweighed filter was placed into the filtration equipment. By means of a vacuum compressed air pump a volume of the dust aerosol 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 of the inhalation atmosphere. The concentration was corrected for the amount of the added excipient.
- Samples taken from breathing zone: yes

TEST ATMOSPHERE
- MMAD (Mass median aerodynamic diameter): 1.9 µm
- GSD: 3.9
Analytical verification of test atmosphere concentrations:
yes
Remarks:
gravimetric determination
Duration of exposure:
4 h
Concentrations:
5.4 mg/L
No. of animals per sex per dose:
10
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: daily
- Body weights: at the beginning of the study, after 7 days and at the end of the study
- Necropsy of survivors performed: yes

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5.4 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: no mortality observed
Mortality:
None of the animals died during the observation period
Clinical signs:
Erratic breathing, slight nasal excretion, ruffled fur during the first 4 days of the observation period, no abnormal findings were observed from day 5 onward.
Body weight:
Normal weight gain.
Day 7, mean weight (g): males: 267; females 201
Day 14, mean weight (g): males: 316; females 211.
Gross pathology:
No abnormal findings.

Any other information on results incl. tables

Results of analytical measurements:

Sample No Analyt. Conc. (mg/l)
1 5.31
2 5.07
3 5.40
4 5.65
Mean 5.4
standard deviation of the mean 0.33
Nominal concentration 39

Particle size analysis:

Stage EACD 50% [µm] [mg] percentage distribution [%] cummulative distribution [%]
pre-impactor 26.6 9.35 2.502 97.498
0 29.5 0.618 2.032 95.466
1 18.2 0.502 6.133 89.333
3 8.5 1.515 13.209 76.124
4 5.5 3.263 18.22 57.904
5 2.8 4.501 18.755 39
7 1.2 4.633 39.149 149
backup filter < 1.2 9.671
Sum 34.053

The MMAD 50% = 1.9 µm (geometrical standard deviation =3.9) was calculated from the results of the particle size analysis.

A respirable dust aerosol fraction that might reach the alveolar region of 89% was obtained from the results of the particle size analysis.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met