Registration Dossier

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This study is classified as reliable without restrictions because it is GLP compliant and was generally conducted according to OECD 403 guidelines.
Justification for type of information:
See read-across justification provided in section 13.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1988
Report Date:
1988

Materials and methods

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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
other: low viscosity liquid hydrocarbon
Details on test material:
- Name of test material (as cited in study report): F-72-01
- Substance type: Petroleum product
- Physical state: Liquid
- Analytical purity: 100% Hydrocarbons
- Density: 0.8751 g/mL
- Lot/batch No.: 2045
- Stability under test conditions: 1 year
- Storage condition of test material: Room temperature

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories, Inc., Kingston, New York 12484
- Age at study initiation: approx. 6 weeks
- Weight at study initiation: 222 to 317 grams (males), 185 to 246 grams (females)
- Housing: Individual
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 1 to 2 weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 24 °C
- Humidity (%): 24 to 91%
- Air changes (per hr): 23 to 28 per hour
- Photoperiod (hrs dark / hrs light): 12 hrs dark / 12 hrs light

IN-LIFE DATES: From: March, 1986 To: June, 1986

Administration / exposure

Route of administration:
other: inhalation: aerosol and vapour mixture
Type of inhalation exposure:
whole body
Vehicle:
air
Details on inhalation exposure:
Nominal concentrations of test article for each exposure determined gravimetrically. Analytical concentration determined using a gravimetric procedure for aerosol level and MIRAN for the vapour level. Actual exposure level is the sum of the aerosol and vapour level. Actual concentrations of the airborne test article measured near the breathing zone at one hour intervals during the exposure period. Particle size distribution measurements made near the breathing zone at one-hour intervals during the exposure period.

The Plexiglas exposure chamber had a total volume of 100L. The airflow rate (1pm) was 17.5, the air change (min) was 5.7 and the equilibrium time (min) was 26.3.
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
2.3, 3.5, or 4.9 mg/L
No. of animals per sex per dose:
Ten
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Twice daily observations of test animals, weekly weighing of test animals
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, histopathology

Results and discussion

Effect levelsopen allclose all
Sex:
female
Dose descriptor:
LC50
Effect level:
3.6 mg/L air (analytical)
Exp. duration:
4 h
Sex:
male
Dose descriptor:
LC50
Effect level:
5.4 mg/L air (analytical)
Exp. duration:
4 h
Sex:
male/female
Dose descriptor:
LC50
Effect level:
4.1 mg/L air (analytical)
Exp. duration:
4 h
Mortality:
Mortality was seen at all doses, within three days following exposure. 11 animals died at the highest dose; 10 animals died at the middle dose; 1 animal died at the lowest dose.
Clinical signs:
other: Signs included labored breathing and gasping during exposure, which continued in the week following exposure, as well as reduced activity, eyes closed, oral and nasal discharge, and matted coats. All surviving animals were normal by day 15.
Body weight:
Body weight gain was decreased in all surviving animals, but values at day 15 generally indicated recovery from treatment.
Gross pathology:
Discoloration of lungs, red staining around snout on spontaneously dying animals.

Applicant's summary and conclusion

Interpretation of results:
harmful
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The inhalation LC50 was determined to be 5.4 mg/L in males, 3.6 mg/L in females, and 4.1 mg/L in combined sexes. The test material is classified as harmful by inhalation according to EU criteria.
Executive summary:

In an acute inhalation toxicity study, groups of young adult Sprague-Dawley rats (10 per sex) were exposed by inhalation route to naval distillate for 4 hours at 2.3, 3.5, or 4.9 mg/L of aerosol. Animals then were observed for 14 days.

 

Animals had laboured breathing and nasal discharge, but survivors were normal by study termination. Following exposure, animals in all groups lost weight, but body weight at study termination indicated recovery. The inhalation LC50 was determined to be 5.4 mg/L in males, 3.6 mg/L in females, and 4.1 mg/L in combined sexes. The test material is classified as harmful by inhalation according to EU criteria.

 

This study received a Klimisch score of one and is classified as reliable without restrictions because the study was GLP compliant and was generally conducted according to OECD 403 guidelines.