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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
other: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
June 1977
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Remarks:
Source study has reliablity 2. Details on the read across are attached in section 13.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1977

Materials and methods

Principles of method if other than guideline:
Test group (10/rat/sex): a single maximum concentration of test substance as a dust by inhalation (nose only) over a period of 4 hours.
Control group (5/rat/sex): atmosphere of filtered air under similar conditions as test group.
GLP compliance:
no
Test type:
fixed concentration procedure

Test material

Constituent 1
Reference substance name:
Similar Substance 01
IUPAC Name:
Similar Substance 01
Test material form:
solid: particulate/powder

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories
- Age at study initiation: aged 7 - 8 weeks
- Weight at study initiation: 180 - 200 g
- Housing: group of 5 by sex
- Diet: ad libitum except during exposure period
- Water: ad libitum except during exposure period
- Acclimation period: 15 days

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 3 °C
- Humidity: 50 ± 10 %
- Air changes: 8 -10 air changes per hour
- Photoperiod: controlled lighting conditions

Administration / exposure

Route of administration:
inhalation: dust
Type of inhalation exposure:
nose only
Vehicle:
other: dried air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Timbrell dust generator
- Exposure chamber volume: 7 litres capacity
- Flow rate: 10 l/min

TEST ATMOSPHERE: mean particle size of the respirable fraction of the atmosphere generated was 1.83 µm.
Analytical verification of test atmosphere concentrations:
yes
Remarks:
gravimetric analysis
Duration of exposure:
4 h
Concentrations:
1.88 mg/l (gravimetric analysis)
43.8 mg/l (nominal concentration)
No. of animals per sex per dose:
test group: 10/sex
control group: 5/sex
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: daily
- Frequency of weighing: 1 day before exposure and on day 1, 2, 4,8, 11 and 15 after exposure.
- Necropsy of survivors performed: yes, if no deaths accurred during exposure, 1 male and 1 female from each group were killed and subjected to gross necropsy.

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 1.88 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Sex:
male/female
Dose descriptor:
LC0
Effect level:
ca. 1.88 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Mortality:
No deaths occurred during exposure or during the observation period as a result of exposure to test substance. One female treated rat suffocated as a result of turning around in the restraining tube. A planned sacrifice was made of 1 male treated rat, 1 male control and 1 female control rat after exposure to assess the degree of primary lung irritation.
Clinical signs:
other: Male and female animals reacted in the same way to the dust. All animals developed chromodacryorrhoea during exposure for a few hours post exposure. The respiration was shallow after exposure but returned to normal an the day after exposure. The faeces we
Body weight:
The mean body weights of the male and female control rats rose throughout the experiment, slowly until day 2 but thereafter more rapidly. The mean body weight of the treated rats was depressed following exposure but rose steadily during the observation period.
Gross pathology:
All control rats and the majority of the treated rats sacrificed after the observation period showed a moderate degree of pulmonary congestion, and pulmonary oedema was noted in some control rats. The female rat which died during exposure and the male rat which was sacrificed immediately after exposure showed only slight pulmonary congestion. No lesions were seen in the other major organs examined.

Any other information on results incl. tables

Atmosphere control

The heterogeneous nature of the article did not facilitate the generation of an atmosphere with a uniformly small particle size. lt is believed that the apparent low percentage transfer of dust from the generator to the sample orifice on the side of the exposure chamber was due to:

(i) deposition of the larger particles on the generator transfer pipe

(ii) production of a heterogeneous atmosphere in the exposure chamber. Observation of the floor of the exposure chamber after exposure showed a higher deposit of dust in the centre. Consequently the atmosphere probably had a higher concentration of aerodynamically less stable, larger particles in the centre. Therefore, samples drawn from the side of the chamber did not contain a representative fraction of all particles produced, but only those which were available to the animals.

Applicant's summary and conclusion

Interpretation of results:
other: CLP Criteria not met
Conclusions:
LC50 > 1.88 mg/l after a 4-hour exposure.
Executive summary:

Method

A single maximum concentration of test substance was given to 20 rats (10 male, 10 female) as a dust by inhalation (nose only) over a period of 4 hours. A further 10 rats (5 male, 5 female) were exposed under similar conditions to an atmosphere of filtered air. The concentration of test substance measured by gravimetric analysis was 1.88 mg/l.

Aerodynamic mass median diameter of dust particles was 1.83 µm.

Results

No substance-related deaths occurred during exposure nor in the following observation period.

All treated animals showed the following signs for 1 -2 days post exposure: chromodacryorrhoea, shallow respiration, discoloured faeces, stained and ruffled fur.

The animals remained alert and their pelts remained stained throughout the observation period. The control animals had chromodacryorrhoea and nasal secretion on the exposure day only. The pelts remained ruffled throughout the observation period.

Mean body weights of male and female control rats rose throughout the experiment, slowly until day 2 but thereafter more rapidly.

The mean body weight of the treated rats was depressed following exposure but rose steadily during the observation period.

Pulmonary congestion was noted in all the control animais. In the treatment group there was a slight to moderate degree of pulmonary congestion in the rats, which were sacrificed at the end of the 14-day observation period.