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Acute Toxicity: inhalation

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acute toxicity: inhalation
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This study was classified as reliable without restriction because it was conducted according to or similar to guideline study OECD TG 403.

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:
acute toxic class method
Limit test:

Test material

Constituent 1
Reference substance name:
Straight run middle distillate (CAS number 64741-44-2)
Straight run middle distillate (CAS number 64741-44-2)
Details on test material:
- Name of test material (as cited in study report): 83-11
- Substance type: Straight run middle distillate
- Physical state: Liquid
- CAS number: 64741-44-2

Test animals

Details on test animals or test system and environmental conditions:
- Source: Charles River Breeding Laboratory
- Age at study initiation: Animals ranged from 9 to 10 weeks
- Housing: Individual stainless steel cages
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: At least 14 days

- Temperature (°C): Room temperature
- Photoperiod (hrs dark / hrs light): 12 hrs dark/ 12 hrs light

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
whole body
other: no data
Details on inhalation exposure:
- Exposure apparatus: Stainless steel glass chamber
- Exposure chamber volume: 0.25 cubic meters
- Method of holding animals in test chamber: Not reported
- Source and rate of air: Clean room air at 2.0 cfm
- System of generating particulates/aerosols: DeVilbis Nebuliser
- Treatment of exhaust air: Not reported
- Temperature, humidity, pressure in air chamber: Not reported

- Brief description of analytical method used: Samples were taken once each hour of exposure by drawing volume of test atmosphere through tared filters. Using the amount of test material found in the filter and the known volume of the air sampled, the exposure concentration was determined.
- Samples taken from breathing zone: Yes

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: Anderson model 2000: cascade impactor
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): (MMAD) 2.05 to 2.4 microns/GSD 1.58 to 1.80 microns
Analytical verification of test atmosphere concentrations:
not specified
Duration of exposure:
4 h
Phase I 5.39 mg/L
Phase II:
Group 1 - 0.01 ( Control)
Group 2 - 1.05 mg/L
Group 3 - 3.22 mg/L
Group 4 - 1.60 mg/L
Group 5 - 2.25 mg/L
No. of animals per sex per dose:
Five males and five females rats were exposed per dose.
Control animals:
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Prior to exposure, at day 7 and day 14 after exposure.
- Necropsy of survivors performed: Yes
- Other examinations performed: Clinical signs, body weight, organ weights, histopathology
No data reported.

Results and discussion

Effect levelsopen allclose all
Dose descriptor:
Effect level:
1.78 mg/L air
95% CL:
1.44 - 2.2
Exp. duration:
4 h
Dose descriptor:
Effect level:
1.72 mg/L air
95% CL:
1.22 - 1.42
Exp. duration:
4 h
Dose descriptor:
Effect level:
1.82 mg/L air
95% CL:
1.45 - 2.28
Exp. duration:
4 h
Phase I 5/5 male and 5/5 females died
Phase II:
Group 1 - 0 males 0 females died
Group 2 - 0/5 males 0/5 females died
Group 3 - 4/5 males died 5/5 females died
Group 4 - 3/5 males died 1/5 females died
Group 5 - 4/5 males died 5/5 females died
Clinical signs:
other: Observation of wet inguinal area, eyes partially closed, wet coat and oily coats were reported.
Body weight:
Dose-related suppression in body weight gain was observed in the day 7 weighing. However, body weight results for Test Week 2 were considered unremarkable.
Gross pathology:
Dark red lungs were reported in all animals which died within a couple days of exposure. Lesions most clearly associated with compound exposure were of an acute nature and were seen only in animals dying within two days following exposure.
All affected animals found dead during the study exhibited diffuse pulmonary congestion and perivascular oedema, spotty alveolar oedema was also seen, but not so consistently. Damage to alveolar walls resulting in fibrinonecrotic debris was also reported.
Necrosis and inflammation were seen in the walls of small blood vessels and there was spotty epithelial necrosis in small bronchioles with the most severe being centroacinar.
Surviving animals did not experience the acute reactions but most survivors exposed to levels of 1.5 mg/L and above exhibited chronic inflammatory
changes that were not seen in controls and only occasionally in animals exposed at the 1.0 mg/L level.
In these animals, there were localized areas of septal hypercellularity characterized by increased numbers of mononuclear inflammatory cells and alveolar cell hyperplasia. Alveoli in affected areas were irregular, often showing mild emphysematous dilatation.

Applicant's summary and conclusion

Interpretation of results:
Migrated information An estimated LC50 value of 1.78 mg/L for the combined sexes and 1.72 mg/L for males rats and 1.82 mg/L for females. Criteria used for interpretation of results: EU
Straight run middle distillate was inhaled by male and female rats for 4 hours at TWA concentrations from 1.05 mg/L to 5.39 mg/L . An estimated LC50 value of 1.78 mg/L for the combined sexes and 1.72 mg/L for males rats and 1.82 mg/L for females.
Executive summary:

Justification for Read Across

Compositional and physico-chemical data show that Other Gas Oils are very similar to Straight-Run Gas Oils. It is considered appropriate, therefore, to read across from the SRGO data to Other Gas Oils.

In an acute inhalation toxicity study, group of young adult Sprague-Dawley rats, 5 male and 5 female in each exposure group, were exposed by inhalation route to straight run middle distillate for four hours to the whole body at concentrations from 1.05 mg/L to 5.39 mg/L . Animals were observed for 14 days.

No animals died in the air only control group or the lowest test material concentration while all the animals exposed to the highest concentration had died by two days post-exposure. Body weight gain depression, pharmacotoxic signs, gross necropsy findings and acute histopathologic changes in the lung were all considered related to treatment. They were most severe in the animals that died 2 to 4 days after exposure. Estimated LC50 values of 1.78 mg/L for the combined sexes and 1.72 mg/L for males rats and 1.82 mg/L for females were calculated.

This study received a Klimisch score of 1 and is classified as reliable without restriction because it was conducted according to or similar to guideline study OECD TG 403.