Registration Dossier

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1996
Report Date:
1996

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:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Butindiol
- Physical state: solid/white to yellow
- Analytical purity: 99.5%
- Lot/batch No.: 41-0701
- Storage condition of test material: Stored in closed bottles covered with N2 in the dark below 30 °C.

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Dr. K. Thomae GmbH, Biberach (FRG)
- Age at study initiation: 8-9 weeks
- Housing: singly; cages type DK III of Becker
- Diet (e.g. ad libitum): ad libitum(KLIBA rat/mouse/hamster laboratory dier 24-343-4 10 mm pellets, Klingentalmuhle AG, Kaiseraugst, Switzerland
- Water (e.g. ad libitum): ad libitum


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24 °C
- Humidity (%): 30-70%
- Photoperiod (hrs dark / hrs light): 12 hours

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose/head only
Vehicle:
other: conditioned air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Head-nose inhalation system INA 20
- Exposure chamber volume: 55 l
- Method of holding animals in test chamber: animals were restrained in tubes and their snouts projected into the inhalation chamber.
- Source and rate of air: the supply air flows were set to 1500 l/h in all test groups.
- System of generating particulates/aerosols: Test solution was supplied to the two-component atomizer by means of the metering pump. By means of compressed air the aerosol was produced in the aerosol mixing vessel and was passed through the cyclonic separator into the inhaltion system.

TEST ATMOSPHERE
- Brief description of analytical method used: gas chromatographical method
- Samples taken from breathing zone: yes

TEST ATMOSPHERE (if not tabulated)
- MMAD (Mass median aerodynamic diameter):: between 0.5 and 1.0 um
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
0.26, 0.23, 0.69, 1.03 mg/l
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
Statistics:
Dose-response relationship was carried out using FORTRAN program AKPROZ: Depending on the data of the dose-response relationship obtained by way of experiment, this program is used to estimate the LC50 or to perform a Probit analysis. Estimation of the LC50 will produce types LC50 greater, LC50 about, or LC50 smaller. If the results are Type LC50 greater or LC50 smaller, an additional binomial test is carried out, in order to verify these statements statistically, if necessary.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
0.69 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Mortality:
0.69 mg/l: 4/5 female rats died
1.03 mg/l: all animals died
Clinical signs:
other: respiratory tract irritation and general toxicity. Animals died without displaying specific symptoms.
Body weight:
Slight depression of female body weight development at the low, low-mid, and mid-high concentration levels. Males body weight development was uneffected at those doses. In the high dose groups, body weight could not be assessed as a result of the mortality.
Gross pathology:
Animals in the high concentration group that died showed red discoloration in the lungs and light brown discoloration of the livers. Animals in the mid-high concentration group that died displayed erosion / ulceration of glandular stomach or general congestion was found. No macroscopic pathologic findings were noted in animals that survived the exposures and were sacrificed.
Other findings:
MMAD was found to be between 0.5 and 1.0 um

Any other information on results incl. tables

Cumulated lethality on day Sex Test group1 (0.26 mg/l)   Test group 2 (0.32 mg/l)   Test group 3 (0.69 mg/l)   Test group 4 (1.03 mg/l)  
0 male 0/5 0/5 0/5 0/5
0 female  0/5 0/5 0/5 0/5
1 male - - 3/5
1 female  2/5 4/5
2 male  - 5/5
2 female - - 4/5  5/5
7 male - - - -
7 female - - - -
14 male - - - -
14 female -  - - -
Total at end of the study male 0/5 0/5 0/5 5/5
Total at end of the study female  0/5 0/5 4/5 5/5

Applicant's summary and conclusion

Interpretation of results:
toxic
Remarks:
Migrated information Category 3 Criteria used for interpretation of results: EU