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Acute Toxicity: inhalation

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acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1982-08-17 to 1982-09-29
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: This study is classified as reliable with restrictions because it is an acceptable and well-documented study report.

Data source

Reference Type:
study report
Report date:

Materials and methods

Test guideline
equivalent or similar to guideline
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
Test type:
standard acute method
Limit test:

Test material

Constituent 1
Reference substance name:
Cas Number:
Constituent 2
Reference substance name:
Hydrodesulfurised middle distillate
Hydrodesulfurised middle distillate
Test material form:
other: low viscosity liquid hydrocarbon
Details on test material:
- Name of test material (as cited in study report): API 81-09 (CAS# 64742-80-9)
- Physical state: clear, pale yellow liquid
- Composition of test material, percentage of components: 46% paraffins, 2.5% olefins, 26.5% napthenes, 25% aromatics
- Storage condition of test material:
- Other: consists of hydrocarbons having carbon numbers predominantly in the range of C11 through C25 and boiling in the range of approximately 205°C to 400°C
- Gravity, degrees API: 38.1
- Sulphur, weight percent: 0.15
- Nitrogen, ppm: <10
- Flash Point, °F: 255
- Boiling range (ASTM D-86) 519 (10%) - 562 (95%) °F
- Initial Boiling Point 502 °F
- End Boiling Point 574 °F

Test animals

Details on test animals or test system and environmental conditions:
- Source: Charles River Laboratories, Portage, Michigan
- Age at study initiation: 63 to 77 days
- Weight at study initiation: not reported
- Fasting period before study: not reported
- Housing: individually housed in suspended wire-mesh cages
- Diet (e.g. ad libitum): ad libitum except during exposure
- Water (e.g. ad libitum): ad libitum except during exposure
- Acclimation period: not reported

- Temperature (°C): 21.7 to 23.3 °C (only test-chamber data were provided)
- Humidity (%): 28 to 48% (only test-chamber data were provided)
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 12 hours light/12 hours dark

IN-LIFE DATES: 1982-08-17 to 1982-09-29

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
whole body
other: air
Details on inhalation exposure:
- Exposure apparatus: glass chambers
- Exposure chamber volume: 54 liters
- Method of holding animals in test chamber: not reported
- Source and rate of air: inhouse compressed air
- Method of conditioning air: filtered for particulates and controlled for temperature and humidity
- System of generating particulates/aerosols: atomizer (Spraying Systems, No. 1650 liquid nozzle and No. 64 air nozzle
- Method of particle size determination: Varian 2440 gas chromatograph
- Treatment of exhaust air: discharged into a fume hood where it was filtered prior to entry into general exhaust system
- Temperature, humidity, pressure in air chamber: pressure not reported; temperature was 21.7 to 23.3 °C and humidity was 28 to 48%

- Brief description of analytical method used: impinger sampling for both aerosol and vapour components; calculated time-weighted average of samples collected from chamber by comparison to standard curve
- Samples taken from breathing zone: no

- Particle size distribution: Andersen 8 stage cascade impactor
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): The equivalent aerodynamic diameter ranged from 3.1 to 4.1 micrometres and the geometric standard deviation ranged from 1.84 to 1.96.
Analytical verification of test atmosphere concentrations:
Duration of exposure:
4 h
actual exposure concentrations were 3.6 mg/L in a preliminary study and 0, 3.5, 4.0, 6.9 and 7.3 mg/L in the definitive test.
No. of animals per sex per dose:
5 animals per sex per dose
Control animals:
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed during exposure and daily in the 14 days following exposure. Body weights were measured just prior to exposure, at 7 and 14 days, and when found dead.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:
LC50 and confidence limits were determined by the method of Bliss and Quart.

Results and discussion

Preliminary study:
In phase 1, five male and five female animals were exposed to 3.6 mg/L of test substance by nose-only exposure for 4 hours and resulted in 60% mortality.
Effect levels
Dose descriptor:
Effect level:
4.6 mg/L air (analytical)
95% CL:
3.92 - 5.4
Exp. duration:
4 h
Table 1 in the remarks section provides mortality data. No deaths occurred during the 4hr exposure period.
Clinical signs:
other: Clinical signs observed during and after exposure include dyspnea, gasping, matted fur, nasal discharge, eyes matted shut, alopecia, open sores, and scabs. The most prevalent clinical signs were dyspnea, nasal discharge, and matted fur.
Body weight:
Conclusions about changes in body weight could not be made due to the number of deaths in each group.
Gross pathology:
A dose-related increase in macroscopic congestion of the lungs of treated animals was observed.
Other findings:
Acute microscopic inflammatory changes of the lungs were observed in the trachea, main bronchi, and alveoli of treated animals.

Any other information on results incl. tables

Table 1 Mortality

Group  Actual Exposure
Concentration (mg/L) 
Male Female Combined Precent Mortality
I  Control 0/5 0/5 0
II  3.6 1/5 5/5 60
III  7.3 4/5 5/5 90
IV  6.9 4/5 4/5 80
V  3.5 0/5 0/5 0
VI  4 1/5 2/5 30

Applicant's summary and conclusion

Interpretation of results:
Migrated information LC50 of 4.6 mg/L air Criteria used for interpretation of results: EU
The LC50 for both males and females was determined to be 4.6 mg/L.
Executive summary:

In an acute inhalation toxicity, male and female Sprague Dawley rats (5/sex/dose) were exposed via whole-body exposure to test material hydrodesulphurised middle distillate at measured concentrations of 0, 3.6, 3.5, 4.0, 6.9, or 7.3 mg/L for 4 hours. The study consisted of two phases; the preliminary phase consisted of 5 males and 5 females exposed to measured concentrations of 3.6 mg/L for 4 hours. The mortality rate for this study was 60%. Four additional test levels were selected for the main study. Animals were observed for 14 days post-exposure followed by a gross macroscopic examination, with microscopic examination of selected tissues including the trachea and lungs. The equivalent aerodynamic diameter ranged from 3.1 to 4.1 µL and the geometric standard deviation ranged from 1.84 to 1.96.


There were no deaths during the 4hr exposure period, and macroscopic and microscopic findings were limited to the lungs, where moderate to severe pulmonary irritation was apparent. Clinical signs commonly included dyspnea and discharge from the nose and eyes. The LC50 for both males and females was determined to be 4.6 mg/L.

This study is classified as a Klimisch score of 2, reliable with restrictions, because it is an acceptable and well-documented study report.