Registration Dossier

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
not reported
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study conducted to an appropriate test guideline with no or minor deviations.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1990
Report Date:
1990

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Lot 2047
Source: Shell International, the Netherlands
Purity: 95.6% cis, 1.5% trans, 0.2% 1,2-dichloropropane
Molecular formula: C3H4Cl2
MOlecular weight: 111 g/mol
Vapor pressure: 34.3 mm Hg at 25C and 760 Torr
Boiling Point: 104 ºC
Physical state: liquid
Maximum vapour concentration: 45131 ppm at 25 ºC

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male/female
Details on test animals and environmental conditions:
Male and female Fischer 344 rats, 6-8 weeks of age, were obtained as stock animals from Charles River Breeding Laboratories, Inc., Kingston, NY.
Selection of this strain and species was based on a variety of considerations including hardiness, low incidence of respiratory disease and historical control data. Upon arrival at the laboratory, the rats were examined for health status by a laboratory veterinarian. The animals were housed two per cage in stainless steel wire cages and acclimated to the laboratory for at least one week prior to exposure. Animals were fed Purina Certified Rodent Chow #5002 (Ralston Purina Co., St. Louis, MO) and water ad libitum except during exposure. Feed and water analysis was performed according to the Standard Operating Procedures of The Toxicology Research Laboratory. All stock animals were randomized by weight into groups of five per sex using a computer randomization program. Animals used for this study were individually identified with alphanumeric metal ear tags. Prior to and after exposure, animals were housed in rooms designed to maintain adequate environmental conditions concerning temperature and relative humidity, and regulated for the specific species under study. A 12-hour photoperiod was employed throughout the study. Animals were singly housed during a 2-week post-exposure period.

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Details on inhalation exposure:
Whole body exposures were conducted in a 157 liter Rochester tyepe stainless stell and glass chamber (50 cm cube with a pyrmidal top and bottom). The air supplied to the chamber was controled by a system designed to maintain temperature and relative humidity at 22 ºC and 50% respectively. Air flow was maintained at approximately 30L/min which was sufficient to provide the normal concentration of oxygen to the animals. Vapors of test material were generated using the glass J-tube method (Miller et al. 1980). Test material was metered at a constant rate into the J-tube. AT the same time, compressed air passed through the J-tube to vaporize the test material. The compressed air was heated to the minimum extent necessary (~50 ºC) to vaporize the test material. Airflow through each chamber was determined with a manometer; temperature, relative humidity and air flow werewere recorded every 30 minutes during the 4-hr exposure period.
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
Target concentrations: 600, 800, and 1000 ppm; measured concentrations: 573, 771, and 1020 ppm
Concentration determined at 30 min intervals with calibrated infrared spectrophotometer at 12.8µm wavelength. The equipment was calibrated with vapor standards of known concentrations prepared by injecting measured voluims of liquid test material in to Saran bags which contained meausured volumes of dry compressed air. The nominal concentration was calculated daily for each chamber.
No. of animals per sex per dose:
5/sex
Control animals:
no
Details on study design:
Chambers:
Whole body exposures were conducted in a 157 liter Rochester type stainless steel and glass chamber (50 an cube with a pyramidal top and bottom). The air supplied to the chambers was controlled by a system designed to maintain temperature and relative humidity at 22°C and 50%,
respectively. Airflow was maintained at approximately 30 liters per minute, which was sufficient to provide the normal concentration of oxygen to
the animals.

Generation System.
Vapors of cis-1,3-dichloropropene were generated using the glass J-tube method (Miller et al., 1980). The test material was metered at aconstant rate into the glass J-tube. At the same time, compressed air passed through the J-tube to vaporize the test material. The compressed air was
heated (Model FHT-, Master Appliance Corporation, Racine, WI) to the minimum extent necessary (- 50°C) to vaporize the test material.

Chamber Monitoring:
Airflow through each chamber was determined with a manometer. The manometer was calibrated with a DTM-115 gas meter
(Singer Aluminum Diaphragm Meter, American Meter Division, Philadelphia, PA) prior to the start of the study. Temperature, relative humidity and airflow values were recorded every 30 minutes during the 4-hour exposure period. The concentration of the test material was determined at 30
minute intervals with an infrared spectrophotometer (Foxboro/Wilks, South Norwalk, CT) at a wavelength of 12.8 urn (major absorption band for cis-DCP). The analytical equipment was calibrated with vapor standards of known concentrations. Vapor standards were prepared by injecting measured volumes of liquid test material into bags made of SARAN" film which contained measured volumes of dry, compressed air. The analytical system was checked prior to each exposure with at least one standard of known concentration. The nominal concentration (ratio of test material used to the total chamber airflow through the chamber) was calculated daily for each chamber. Prior to exposure of animals to cis-DCP, the distribution of test material was determined from at least 5 sample points in the breathing zone and the reference point in the chamber.

Exposure Concentration:
Groups of 5 male and 5 female rats were exposed for 4-hours to target concentrations of 600, 800 or 1000ppm which correspond to
analytical concentrations of 573, 771, or 1020 ppm cis-DCP. The additional exposures were performed at the request of the sponsors to meet OECD guidelines.

Observations and Criteria of Response:
Animals were weighed and examined prior to exposure to the test material; this included a penlight ophthalmic examination by a laboratory veterinarian. All animals were observed during the exposure period (not always possible due to cage placement) and daily (except weekends or holidays) during the two-week post-exposure period. The observations included an evaluation of fur, eyes, mucous membranes, and respiration. Behavior pattern and nervous system activity were also assessed by specific observation for tremors, convulsions, salivation, lacrimation, and diarrhea, as well as lethargy and other signs of altered central nervous system function. Daily observations in the morning and routine monitoring on weekends and holidays were limited to the removal of dead animals and husbandry procedures required to ensure the availability of food and water. All surviving rats were weighed on test days 2, 4, 8, 11, and 15 during the two-week post-exposure period. All rats were submitted for a complete gross necropsy examination. Tissues were not saved.
Statistics:
Means and standard deviations of body wieght and chamber temperature, relative humididty and airflow were caluclated. The LC50 was determined by non-linear interpolation (Stephan 1977).

Results and discussion

Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LC50
Effect level:
670 ppm
Based on:
test mat.
Exp. duration:
4 h
Sex:
female
Dose descriptor:
LC50
Effect level:
744 ppm
Based on:
test mat.
Exp. duration:
4 h
Mortality:
All animals died during or shortly after exposure to 1020 ppm. In the 771 ppm exposure group, 2 male rats died during or within 30 min of exposure and 3 more males and 3 females died within the first 4 days of the 2-week observation period. All rats in the 583 ppm exposure group survived.
Clinical signs:
other: All animals exposed to 583, 771, or 1020 ppm had labored breathing, at the lowest concentration, the labored breathing was reversible and not observed 2 h after exposure. Several animals exposed to 583 pppm were noted to have eye irritation during the ex
Body weight:
Body weights for 2 surviving female rats were decreased following expsoure to 771 ppm. However both females were gaining weight by day 15. Body weights of rats exposed to 583 ppm decrease 11-13% on test day 2, but were gaining weight by test day 8.
Gross pathology:
5 animals exposed to 1020 ppm had corneal opacities noted at necropsy. Pulmonary edema was noted in all rats exposed to 1020 ppm and 3 animals exposed to 771 ppm. 2 animals exposed to 771 ppm exhbited hydrotorax, and several animals exhibited facial soiling and perineal soiling. There were no grossly visible lesions noted in animals surving until the end of the 2-wk post-exposure period.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The approximate LC50 for male and female rats is 670 and 744 ppm cis-DCP, respectively, based on nonlinear interpolation.
Executive summary:

A GLP-compliant study has been conducted according to OECD Guideline 403. The approximate LC50 for male and female rats is 670 and 744 ppm cis-DCP respectively based on non linear interpolation.