Propan-2-ol

Acute Toxicity: inhalation

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

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

Test material information

Constituent 1

Reference substance name:

Propan-2-ol

EC Number:

200-661-7

EC Name:

Propan-2-ol

Cas Number:

67-63-0

Molecular formula:

C3H8O

IUPAC Name:

propan-2-ol

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 or test system 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 levels

Effect levels 1

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

Effect levels 2

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

Effect levels 3

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 10 000 ppm

Exp. duration:

6 h

Mortality:

none

Clinical signs:

other: 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

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:

GHS criteria not met

Remarks:

for acute toxicity

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