Registration Dossier

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
Not stated
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study was conducted prior to test guidelines and GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1967
Report Date:
1967

Materials and methods

Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
Rats were exposed to vapors generated from test material heated at 200C. Exposure time ranged from 1 to 7 hours
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
not specified
Details on test material:
- Name of test material (as cited in study report): Glycerine
- Substance type: not specified in the report
- Physical state: not specified in the report
- Analytical purity: not specified in the report
- Impurities (identity and concentrations): not specified in the report
- Composition of test material, percentage of components:not specified in the report
- Isomers composition: not specified in the report
- Purity test date: not specified in the report
- Lot/batch No.: not specified in the report
- Expiration date of the lot/batch: not specified in the report
- Stability under test conditions: not specified in the report
- Storage condition of test material: not specified in the report

Test animals

Species:
rat
Strain:
not specified
Sex:
male
Details on test animals and environmental conditions:
No additional information available.

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
air
Details on inhalation exposure:
Saturated vapor atmosphere generated by passing compressed air throught the test material contained in a fritter-finger glass bubbler immersed in an oil bath heated tp approximately 200°C and introduced into the exposure chamber. For the L(Ct)50 experiment, the same vapor was mixed with room air (1:1) before introduction into the exposure chamber.
Analytical verification of test atmosphere concentrations:
no
Duration of exposure:
>= 1 - <= 7 h
Concentrations:
Nominal concentration 11.0 mg/L
No. of animals per sex per dose:
Groups of 5 rats were exposed for 1, 2 and a maximum of 7 hours.
Control animals:
not specified
Details on study design:
No additional information available.
Statistics:
No additional information available.

Results and discussion

Preliminary study:
Not applicable.
Effect levels
Sex:
male
Dose descriptor:
other: L(Ct)50
Effect level:
4 655 other: mg-min/liter
Based on:
test mat.
Exp. duration:
7 h
Mortality:
See below.
Clinical signs:
other: No additional information available.
Body weight:
No additional information available.
Gross pathology:
See below.
Other findings:
No additional information available.

Any other information on results incl. tables

In a preliminary study, no mortality was observed in rats exposed to a saturated vapor for 1 hour and all animals died within 48 hours after exposure to a saturated vapor for 2 hours.

In the L(Ct)50 experiments, compressed air at the rate of 500 ml/minute was bubbled through glycerine which was heated to 200C. The rate of vaporization of glycerine under these conditions, was gravimetrically determined and calculated to be 11.0 mg/minute. The vapor-laden air was diluted by adding make-up air at the rate of 500 ml/minute. The total airflow (volume of air emerged from heated compound plus the volume of make-up air added per unit time), entering the exposure chamber was 1 liter/minute. The nominal concentration of glycerine in the experimental atmosphere was therefore 11.0 mg/L.

During the initial four hours of exposure, no significant adverse effect was observed. However, after approximately 240 minutes, signs of mild irritation, indicated by hyperemia of the eyelids and nasal discharges were observed. These conditions became more severe as the exposure progressed. The animals eventually salivated profusely and exhibited dyspneic respiratory patterns. After approximately 360 minutes, all animals began gasping for air and lay in prostration. Two animals died at approximately the 419 minute timepoint. The third one died shortly after the termination of the exposure. The fourth animal succumbed at approximately 30 minutes post-exposure. The remaining animal succumbed on the fourth post-exposure day. Based upon the time-to-death data, an approximate Lt50 was graphically determined to be 423 minutes.

The L(Ct)50 was obtained by multiplying the nominal chamber concentration, C, with the estimated Lt50 and was equal to 4655 mg-min/liter.

Necropsies of the animals which succumbed revealed: 1) desquamation of the epithelium of the trachea, 2) hyperemia and slight edema of the lung tissues, and 3) extreme distention of the stomach and intestines with air. No significant gross pathological condition was detected in other organs or tissues.

Applicant's summary and conclusion

Interpretation of results:
Category 5 based on GHS criteria
Remarks:
Migrated information
Conclusions:
Under the conditions of the study, the acute inhalation exposure of rats for two hours to saturated vapors generated at 200°C produced 100 per cent mortality, while for exposures of one hour, no mortality was observed. The nominal concentration was 11 mg/L and this study is of a condensation aerosol. Thus the 1 hour LC50 based on nominal concentration was >11 mg/L. Under the OECD GHS guidelines, a 4 hr LC50 can be determined from a 1 hour LC50 by dividing by 4. Thus a calculated 4 hour LC50 value based on nominal concentration would be >2.75 mg/L.
Executive summary:

The acute toxicity following 1 or 2 hours exposure to saturated vapors of glycerine (generated by passing air through test material heated to 200C) was determined. Under the conditions of the study, the acute inhalation exposure of rats for two hours to saturated vapors generated at 200°C produced 100 per cent mortality, while for exposures of one hour, no mortality was observed. The nominal concentration was 11.0 mg/L and this study is of a condensation aerosol. Thus the 1 hour LC50 based on nominal concentration was >11.0 mg/L. Under the OECD GHS guidelines, a 4 hr LC50 can be determined from a 1 hour LC50 by dividing by 4. Thus a calculated 4 hour LC50 value based on nominal concentration would be >2.75 mg/L.

In addition the L(Ct)50 was determined following exposure to 1100 mg/L. The L(Ct)50 for Glycerine was 4655 mg minute/liter.