Registration Dossier

Toxicological information

Acute Toxicity: inhalation

Currently viewing:

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
not specified
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: This study was conducted in accordance with GLP guideline(DOT) and sufficient data is available for the interpretation of study results.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1985
Report Date:
1985

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: DOT guidelines
Deviations:
no
Principles of method if other than guideline:
The 1 hour LC50 was determined for Epichlorohydrin in male and female rats
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
99.9% purity

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male/female
Details on test animals and environmental conditions:
Source: Charles River Breeding Laboratories, Kingston, NY
Age: 6-8 weeks
Weight at study initiation: males: 177-266 g; females: 126-148 g
Number of animals: 6/sex/exposure concentration

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
ADMINISTRATION:
Type of Exposure: whole-body vapor exposures
Concentrations:
Target 500 1000 2000 2800 3350 4000
Nominal 599 1133 2329 3306 3866 4609
Analyt. 552 1008 1970 2865 3275 3995
Males only were exposed to analytical concentrations of 2865 and 3275 ppm.

Exposur es occurred in 2.6 cubic meter Rochester-type inhalation chambers. Atmospheres were generated by passing heated compressed air through a J-tube assembly as the test material entered the J-tube assembly. Chamber airflow was maintained at 400-500 liters/hour. Chamber concentrations were monitored 7 times/hour using gas chromatography.
Analytical verification of test atmosphere concentrations:
yes
Remarks:
gas chromatography
Duration of exposure:
1 h
Concentrations:
Target 500 1000 2000 2800 3350 4000
Nominal 599 1133 2329 3306 3866 4609
Analyt. 552 1008 1970 2865 3275 3995
Males only were exposed to analytical concentrations of 2865 and 3275 ppm.
No. of animals per sex per dose:
6/sex/exposure concentration
Control animals:
no
Details on study design:
Animals were observed for signs of toxicity during exposure and for 14 days post-exposure. Animals were weighed at study initiation, and surviving rats were weighed on study days 2, 4, 8, 11, and 15. All animals were submitted for pathological examination of major organ systems either at death or at study termination. In addition, nasal cavities were split longitudinally for examination of the turbinate area.
Statistics:
The LC50 for females was calculated as a function of the time-weighted average analytical exposure concentrations by the moving-average method (Thompson and Weil, 1952). The LC50 for males was estimated by calculating the geometric man between exposure levels that resulted in 0 and 100% mortality among males, as implemented in a computer program furnished by Dr. Charles E. Stephan, USEPA Environmental Research Laboratory, Duluth, MN.

Based on the mortality observed in this study, a LC50 value for male
rats could not be calculated using the moving average method because there were no partial kills (Thompson and Weil, 1952). As an alternative, the LC50 for males was estimated by calculating the geometric mean between exposure levels that resulted in 0 and 100% mortality among male rats (i.e., 3275 and 3995 ppm, respectively), as implemented in a computer program furnished by Dr. Charles E. Stephan, USEPA Environmental Research Laboratory, Duluth, MN.

Results and discussion

Preliminary study:
not applicable
Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LC50
Effect level:
ca. 3 617 ppm
Exp. duration:
1 h
Remarks on result:
other: no mortality observed at 3275 ppm and all rats died at 3995 ppm
Sex:
female
Dose descriptor:
LC50
Effect level:
2 165 ppm
Exp. duration:
1 h
Mortality:
MORTALITY:

# Dead/# Treated Time to Death
Dose Male Female Male Female
(PPM) CDF CDF CDF CDF
552 0/6 0/6 --- ---
1008 0/6 0/6 --- ---
1970 0/6 2/6 --- 1@2 days
1@3 days
2865 0/6 --- --- ---
3275 0/6 --- --- ---
3995 6/6 6/6 3@1 day 6@1 day
1@2 days
1@3 days
1@4 days

---: not tested
Clinical signs:
other: Signs of toxicity were predominantly noted at exposure concentrations of 1970 ppm and above, although all rats exposed to 1008 or 552 ppm spent most of their exposure time huddled in their cages with eyes completely shut. Signs of eye and nasal irritation
Body weight:
Body weights were essentially unaffected following exposure to 552 ppm with animals gaining weight. At higher concentrations, rats lost weight immediately following exposure but survivors gained weight thereafter.
Gross pathology:
The most frequent observation noted at necropsy among male rats surviving the 2-week observation period was bilaterial corneal cloudiness at 1970 ppm (1/6), 2865 (5/6), or 3275 (6/6). No other observations noted were considered to be treatment-related.
Other findings:
POTENTIAL TARGET ORGANS: Eye.

SEX-SPECIFIC DIFFERENCES: None other than differing LC50's

Any other information on results incl. tables

Six rats/sex/exposure level were exposed to time-weighted average (TWA) analytical concentrations of 552, 1008, 1970 or 3995 ppm (2.088, 3.814, 7.453 or 15.114 mg/l, respectively) ECH vapors for l-hr. Two additional groups of 6 male rats were also exposed to TWA concentrations of 2865 or 3275 ppm (10.839 or 12.390 mg/l, respectively). The l-h r LC50 for male rats was estimated to be 3617 ppm. For females, a l-h r LC50 of 2165 ppm was calculated by the moving average method of analysis. Eye and nasal irritation, respiratory difficulty and secretion of a reddish, porphyrin-like material on the facial area were noted among rats exposed to 1970, 2865, 3275 or 3995 ppm, Hyperactivity, followed by lethargy and a cyanotic appearance were also noted in rats exposed to 3275 or 3995 ppm, Although a temporary body weight loss was evident in almost all exposure groups, all rats that survived a 2 -week observation period steadily gained weight. Bilateral corneal cloudiness was the only exposure-related lesion noted among animals (males only) surviving to scheduled necropsy.

Applicant's summary and conclusion

Interpretation of results:
Category 3 based on GHS criteria
Conclusions:
Based on the results of the study the 1 hour LC50 values of ECH in male and female Fischer-344 rats were not only greater than 1000 ppm ppm but
also greater than 1/10th of maximum saturated vapor concentration of ECH at 20c which is calculated to be 17,100 ppm.
Executive summary:

The purpose of this study was to determine the single-exposure 1-hr LC50 of epichlorohydrin (ECH) in Fischer-344 rats. These data were requested in response to recently proposed Department of Transportation (DOT) guidelines that would require additional labeling for the transportation of any liquid whose 1 -hr LC50 values in male and female rats are: 1) less than or equal to1000 ppm; and 2) less than or equal to 1/10th of the liquid's theoretical saturated vapor concentration at 20°C.

Six rats/sex/exposure level were exposed to time-weighted average (TWA) analytical concentrations of 552, 1008, 1970 or 3995 ppm (2.088, 3.814, 7.453 or 15.114 mg/l, respectively) ECH vapors for 1 -hr. Two additional groups of 6 male rats each were also exposed to TWA concentrations of 2865 or 3275 ppm (10.839 or 12.390 mg/l, respectively). The 1-hr LC50 for male rats was estimated to be 3617 ppm. As calculated by the moving average method of analysis, the LC50 for females was 2165 ppm.

Based on the results of this study, ECH does not meet the proposed DOT criteria that would require additional labeling for transportation. The 1-hr LC50 values of ECH were not only greater than 1000 ppm, but also greater than 1/10 of the maximum saturated vapor concentration of ECH at 20°C (calculated to be 17,100 ppm).