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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:
14d
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland GmbH
- Age at study initiation: About 9 weeks
- Housing: Single caging in Makrolon cages type III
- Diet (e.g. ad libitum): Ssniff R/M-H maintenance diet
- Water (e.g. ad libitum): Tap water or acidified water to pH 3 with HCl, from Makrolon-bottles or from a watering system, ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 °C
- Humidity (%): 50 %
- Photoperiod (hrs dark / hrs light): Artificial light from 6.00 a.m. to 6.00 p.m.

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: The apparatus consists of a two-chamber system and is equipped with 20 outlets for inhalation tubes
- Exposure chamber volume: 30 cm in diameter and 27 cm high, resulting in a volume of 19 L.
- Rate of air: 600 L/h
- System of generating particulates/aerosols: From TSE Systems GmbH, Bad Homburg, dust generator according to Bundschuh
- Method of particle size determination:
- Treatment of exhaust air:
- Temperature, humidity: 22ºC, 30-70%.
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
>= 1 - <= 4 h
Concentrations:
0.45, 0.95 and 2.35 mg/L
No. of animals per sex per dose:
5 males and 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Behaviour and clinical signs each hour during the application and 1 h and 2 h after the exposure, then once a day until the end of the study
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights, histopathology

Results and discussion

Effect levelsopen allclose all
Sex:
female
Dose descriptor:
LC50
Effect level:
ca. 2.021 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Sex:
male
Dose descriptor:
LC50
Effect level:
ca. 1.673 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Sex:
male/female
Dose descriptor:
LC50
Effect level:
ca. 1.814 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Mortality:
All animals of the low and the mid concentration group survived till the end of the study. In the high concentration group 3 males and 3 females died 1 to 4 days after the exposure. One other animal was killed because of its moribund state on day 3 after the exposure.
Clinical signs:
other: The females of the low concentration group had no symptoms during the whole observation period. In all other groups symptoms were observed. Most prominent findings were signs of reduced well-being (apathy, piloerection, arched back) and chromodacryorrhoea
Body weight:
The animals lost weight the first week after the exposure. This is in good agreement with the observed symptoms of the animals. In the second week all but two animals gained weight again.
There is no clear correlation between the dust concentration and the body weight gain between the low and mid concentration. There is however a substantial higher body weight loss in the high concentration group the first days after the exposure.
Other findings:
The symptoms were the same in both sexes but the degree of severity was higher in males in this study.

Any other information on results incl. tables

In the low and mid dose no animal died. In the high dose 4 males and 3 females died. The LC50 is therefore 1.673 mg/L for males, 2.021 mg/L for females and 1.814 mg/L for both sexes. In respect to mortalities the NOEC was the mid concentration, 0.95 mg/L. In respect to in-life observations however there was no NOEC as also in the low concentration symptoms like respiratory murmur, chromodacryorrhoe, unusual weight loss, etc. occurred.

Applicant's summary and conclusion

Interpretation of results:
toxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Executive summary:

 

sex

concentration

number of animals

 

mg/L

dead

affected*

exposed

male

0.45

0

4

5

female

0.45

0

0

5

male

0.95

0

5

5

female

0.95

0

5

5

male

2.35

4

5

5

female

2.35

3

5

5

* according to in-life observations and necropsy findings.

 

LC50, inhalation, 4 h, male rats: 1.67 mg/L(95 % confidence limits: 1.26 to 2.22 mg/L)

LC50, inhalation, 4 h, female rats: 2.02mg/L(95 % confidence limits: 1.09 to 3.74 mg/L)

LC50, inhalation, 4 h, both sexes: 1.81mg/L(95 % confidence limits: 1.37 to 2.41 mg/L)