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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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1979
Report Date:
1979

Materials and methods

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

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: WIGA, Sulzfeld, Germany
- Weight at study initiation: 187 g (males), 204 g (females)
- Diet: Herilan MRH (Eggersmann KG, Rinteln/Weser, Germany), ad libitum
- Water: tap water, ad libitum

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose/head only
Vehicle:
not specified
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: dynamic head-nose apparatus (BUNDSCHUH, Griesheim, Germany) and constant infusion apperatus (UNITA I, BRAUN, Melsungen, Germany)
- Rate of air: 1000 L/h

TEST ATMOSPHERE
- Brief description of analytical method used: for the quantitative analysis an indirect indicator method was used. Therefore, the substance was mixed with 0.06 and 0.19% Oil Res 0 C.J. 26125. The samples were measured spectroscopically at 525 nm and the concentration of the test substance was evaluated using a calibration line.
- Samples taken from breathing zone: yes
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
0.3, 0.6, 2.2 and 3.7 mg/L (analytical concentration)
0.95, 1.67, 11.4 and 22.7 mg/L (nominal concentration)
No. of animals per sex per dose:
10
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: animals were observed daily for mortality and individual body weights were determined before start of the study and thereafter weekly
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
The statistical analysis was performed according to the "Probitanalyse" (D.J. Finney, 1971, Syndics of the Cambridge University Press, London, UK).

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LC50
Effect level:
1.37 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Sex:
female
Dose descriptor:
LC50
Effect level:
1.8 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Sex:
male
Dose descriptor:
LC50
Effect level:
ca. 1.05 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Mortality:
0.6 mg/L: 3 males and 1 female animal died
2.2 mg/L: 10 males and 4 females died
3.7 mg/L: 8 males and 10 females died
Clinical signs:
0.3 mg/L: flight attempts and gasping breathing
0.6 mg/L: additional to the signs of the low dose group and noisy breathing and slight staggering. One female showed lateral position.
2.2 mg/L: additional to the signs of the 0.6 mg/L dose group and bloody nose area, low motility, hair loss in the head area.
3.7 mg/L: additional to the signs of the 2.2 mg/L dose group and salivation. One female showed ventral position, abusive pain reflex and cowering position.

All animals were free of symptoms from Day 2-8 after treatment.
Body weight:
2.2 mg/L (females): weight loss (mean 8 g) from Day 7-14
3.7 mg/L (males): weight loss (mean 4 g) from the Day of exposure to Day 7
Gross pathology:
Animals that died during the study period:
0.6 mg/L: heart: acute dilatation, acute hyperemia; lung: oedema with emphysema at the edges, pulmonary lobes were wet and fleshy and excess of blood were observed
2.2 mg/L: acute dilatation, acute hyperemia; lung: severe exhalation especially at the peripheral areas, severe oedema formation, single areas wet and fleshy. One animal with slight hydrothorax
3.7 mg/L: acute dilatation, acute hyperemia; lung: laminar bleedings, slight exhalation

Surviving animals:
Organs showed no signs of toxicity.

Any other information on results incl. tables

Table 1. Table for acute inhalation toxicity.

Target concentration
[mg/L air]

Toxicological results*

Duration of clinical signs

Mortality (%)

Males

0.3

0/10/10

Day 2-7

0

0.6

3/10/10

Day 2-7

30

2.2

10/10/10

Day 2-7

100

3.7

8/10/10

Day 2-7

80

Females

0.3

0/10/10

Day 2-7

0

0.6

1/10/10

Day 2-7

10

2.2

4/10/10

Day 2-7

40

3.7

10/10/10

Day 2-7

100

LC50 = 1.37 (1.01-1.85) mg/L air

* first number = number of dead animals

 second number = number of animals with clinical signs

 third number = number of animals used

Applicant's summary and conclusion

Interpretation of results:
other: Acute tox. Inhalation 4, H332. Classification according to Regulation (EC) No. 1272/2008 (CLP/EU GHS).