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Toxicological information

Acute Toxicity: inhalation

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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
June 6, 1983
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The GLP study was not conducted according to guideline/s but the report contains sufficient information to permit a meaningful evaluation of study results
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1983
Report Date:
1983

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
none
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): Propylene dichloride
- Substance type: solvent, chemical intermediate and fumigant
- Physical state: liquid
- Analytical purity: 99 %
- Lot/batch No.: 82TA 820401 LSS

Test animals

Species:
other: rat and mice
Strain:
other: Fischer 344 rats and B6C3F1 mice
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Fischer 344 rats and B6C3F1 mice (Charles River Breeding Laboratories)
- Age at study initiation: 16-17 weeks old
- Weight at study initiation: rats (mean: 279-286 g), mice (mean: 30-32 g)
- Housing: not specified in the report
- Diet (e.g. ad libitum): ad libitum, except during exposure
- Water (e.g. ad libitum): ad libitum, except during exposure

ENVIRONMENTAL CONDITIONS
- Temperature (°C): not specified in the report
- Humidity (%): not specified in the report
- Air changes (per hr): not specified in the report
- Photoperiod (hrs dark / hrs light): not specified in the report

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: Glass J-tube method
- Exposure chamber volume: 4.3 m3 stainless steel and glass Rochester-type chambers
- Source and rate of air: filtered air, chamber airflow maintained at ~ 800 l/min
- Method of conditioning air: flitered
- Temperature, humidity, pressure in air chamber: maintained at approximately 70 °F and 50 %.


TEST ATMOSPHERE
- Brief description of analytical method used: The concentration of propylene dichloride in each exposure chamber was determined at least 2 times/hr with a MIRAN 1A infrared spectrophotometer at a wavelength of 9.8 µ. The concentration of propylene dichloride in the chamber was determined by interpolation from a standard curve derived from known air standards.
- Samples taken from breathing zone: not specified in the report


Analytical verification of test atmosphere concentrations:
yes
Remarks:
The analytical time weighted average concentrations for the single 6-hour exposure were 500 and 1498 ppm for the targeted concentrations of 500 and 1500 ppm.
Duration of exposure:
ca. 6 h
Concentrations:
500 and 1500 ppm
No. of animals per sex per dose:
5 males rats/mice per dose
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 4 days
- Frequency of observations and weighing: All animals observed before, during and after exposure. Bodyweights recorded on the day of exposure, days 2 and 4
- Necropsy of survivors performed: yes
- Other examinations performed: gross pathology and histopathology
Statistics:
No statistical analyses performed

Results and discussion

Preliminary study:
none
Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LC50
Effect level:
500 ppm
Exp. duration:
6 h
Remarks on result:
other: B6C3F1 mice
Sex:
male
Dose descriptor:
other: LC50 could not be determined
Effect level:
500 - 1 500 ppm
Exp. duration:
6 h
Remarks on result:
other: Fischer 344 rats
Mortality:
Rats - no mortality
Mice - All mice (5/5) exposed to 1500 ppm died within 24 hours post exposure and 2/5 mice exposed to 500 ppm died during the post exposure period
Clinical signs:
Rats - 1500 ppm - appeared anesthetized/lethargic during exposure, 500 ppm - all animals appeared normal
Mice - 1500 ppm - mortality within 24 hours post exposure, 500 ppm - surviving animals appeared normal
Body weight:
Rats - 1500 ppm - slightly greater body weight loss as compared to control animals on the day of exposure, howvever, subsequent body weight gain comparable to controls. 500 ppm - comparable body weights to controls
Mice - 500 ppm - comparable body weights to controls
Gross pathology:
Rats - 1500 ppm - slight pallor of the liver observed in 4/5 rats, 500 ppm - no gross pathological changes observed
Mice - 1500 ppm - no gross pathological changes 5/5 (found dead), 500 ppm - grossly visible liver lesions 2/3 (terminal sacrifice)
Other findings:
- Histopathology:
Rats - slight pallor of liver noted was correlated histopathologically with a slightly increased degree of microvacuolization of the hepatocytes. other changes noted in liver and kidney were considered normal.
Mice - Gross indications (varied intensity) of hepatotoxicity with extensive acute hemorrhagic coagulation necrosis of the liver seen in 2/3 surviving animals exposed to 500 ppm

Any other information on results incl. tables

see the attached word doc. for tables and figures:

Applicant's summary and conclusion

Interpretation of results:
harmful
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the results of the study, Propylene dichloride may be classified as harmful by inhalation, according to Annex VI-Directive 67-548/EEC.
Executive summary:

An Acute Vapor Inhalation Toxicity Study (no guidelines followed) and conforming to GLP) of Propylene Dichloride (purity: 99% and lot no.: 82TA 820401 LSS) in male Fischer 344 rats and B6C3F1 mice (16-17 weeks old), sourced from Charles River Breeding Laboratories, were exposed to 0, 500 and 1500 ppm for a single 6-hour exposure. The analytical time weighted average concentrations for the single 6-hour exposure were 500 and 1498 ppm, respectively. Animals were acclimated to laboratory conditions and were housed in standard conditions and fed with standard diet (Certified Purina Chow #5002) and water provided ad libitum, except during exposure. Parameters evaluated were during the 4-day observation period included body weights and in-life observations. All animals were examined for gross pathological changes.

Rats exposed to 1500 ppm were lethargic during exposure, lost weight and exhibited pale liver on gross examination. All mice exposed to 1500 ppm died within 24-hours post-exposure and exhibited non-specific changes typical of animals which die in acute studies. Several mice exposed to 500 ppm of propylene dichloride died and exhibited various degrees of liver toxicity upon gross and histopathological examination. The acute LC50 for mice was determined to be approximately 500 ppm with observation of liver toxicity. Also, species differences in sensitivity of rats and mice were observed.