Registration Dossier

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1991
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Well documented, according to accepted guidelines

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1991
Report Date:
1991

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
6 hr exposure period instead of 4 hr, 14-day observation period was not clearly stated
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): isopropanol
- Physical state: liquid
- Analytical purity: approximately 100%
- Storage condition of test material: stored in an outside storage area or the chemical storage room

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Spague-Dawley, Inc. (Indianapolis, IN)
- Age at study initiation: 9 to 11 weeks
- Housing: individually in stainless stell wire mesh cages
- Diet (e.g. ad libitum): Ground Purina Certified Rodent Chow ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: approximately one week


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 to 25
- Humidity (%): 40 to 70
- Photoperiod (hrs dark / hrs light): 12/12


Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: stainless steel chambers with glass doors and windows
- Exposure chamber volume: Four approximately 1330-liter and one approximately 900-liter
- Source and rate of air: filtered air at a flow rate of approximately 14 air changes per hour
- Temperature, humidity in air chamber: recorded approximately 12 times during each exposure

TEST ATMOSPHERE
- Brief description of analytical method used: flame ionization gas chromatographic (GC) technique
- Samples taken from breathing zone: yes



Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
ca. 6 h
Concentrations:
500, 1500, 5000, 10000 ppm
No. of animals per sex per dose:
25 animals/sex/dose
Control animals:
yes
Details on study design:
- Duration of observation period following administration: twice daily, beginning on the day of after exposure and continuing until sacrifice
- Frequency of observations and weighing: body weights were recored prior to exposure and during each test session
- Necropsy of survivors performed: no
Statistics:
The data for continuous, parametric variables were intercompared for the dose and control groups by use of Levene’s test for homogeneity of variances,by analysis of variance, and by pooled variance t-tests. The t-tests were used, if the analysis of variance was significant (P
Intra-session motor activity data was analyzed using a repeated measures analysis with dose as grouping factor and session time as the within subject factor. Group comparisons at each reporting epoch were made (as described above) if significant dose effects or time by dose interactions were observed.
The epsilon-adjustment procedure (Greenhouse-Geisser correction) was used in repeated measures analysis of motor activity data.
Frequency data from FOB tests was evaluated using Fisher’s exact
probability test.

All statistical tests were performed using BMDPm Statistical Software (Dixon, 1985 or Dixon, 1988). The fiducial limit of 0.05 was used as the critical level of significance for all tests.

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
other: transient, concentration-related narcosis and/or central nervous system sedation
Effect level:
ca. 5 000 ppm
Exp. duration:
6 h
Sex:
male/female
Dose descriptor:
other: transient, concentration-related narcosis and/or central nervous system sedation
Effect level:
ca. 10 000 ppm
Exp. duration:
6 h
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 10 000 ppm
Exp. duration:
6 h
Mortality:
none
Clinical signs:
In the 10000 ppm group, prostration, severe ataxia, decreased arousal, slowed or labored respiration, decreased neuromuscular tone, hypothermia, and loss of reflex function was observed 1 and 6 hours after exposure. Concentration-related decreases in mean motor activity were observed for males in the 1500, 5000, and 10000 ppm groups and females in the 5000 and 10000 ppm groups. Motor activity was severely depressed for males and females in the 10000 ppm group. Concentration-related decreases in motor activity were observed for males and females in the 5000 ppm group, and minor decreases in motor activity were observed for males in the 1500 ppm group.
Body weight:
Body weight was measured at the time of behavioral testing so that any possible confounding effect that body weight might have on behavior could be assessed. Mean body weights for the five exposure groups were not statistically significantly different at any time during the study. Mean body weight tended to be lower for animals in the 10000 ppm exposure group assigned to FOB testing at the 6-hour and 24-hour post-exposure evaluations. This decrease is considered to reflect decreased food consumption during the time period when prostration and narcosis were observed.

Gross pathology:
none

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: other: CLP (EC 1278/2008)
Conclusions:
LC50 > 10000 ppm
Executive summary:

Due to transient concentration-related narcosis and central nervous system sedation effects, the substance should be classified under STOT single exposure category 3, H336 - may cause drowsiness or dizziness, according to CLP classification criteria