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Toxicological information

Acute Toxicity: inhalation

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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
1985-02-06 to 1985-06-06
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This study is classified as reliable without restriction because it closely followed OECD guideline 403.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1986
Report Date:
1986

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:
Test substance (as identified in study report): API 83-08 (CAS# 64741-59-9)
Physical description: brownish coloured liquid
Storage: refrigerated at 4°C
Gravity API: 24.2
Nitrogen, ppm: 312
Flash point: 142 °F
Viscosity at 40°C cST: 2.8


Paraffins 22.3%
Olefins 5.5%
Naphthenes 10.7%
Aromatics 61.5%
Saturates 33.0%

Distillation ASTM D86 Equivalent:
Initial Boiling Pt °F: 382
Boiling Pt Range (10-90%): 466-603
Final Boiling Pt °F: 642

Test animals

Species:
rat
Strain:
other: COBS CD (SD) BR
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories, Inc., Kingston, New York
- Age at study initiation: approximately 9 to 12 weeks old
- Weight at study initiation: approximately 282 to 373 grams for males and between 179 to 259 grams females
- Fasting period before study: not reported
- Housing: individually housed in stainless steel hanging wire cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 14 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 to 24°C
- Humidity (%): 50 to 68%
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 12 hours light/12 hours dark


IN-LIFE DATES: From: 1985-02-06 To: 1985-06-06

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
whole body
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: chambers with square cross-sectional area and pyramidal top and base.
- Exposure chamber volume: 0.25 m3
- Method of holding animals in test chamber: not reported
- Source and rate of air: clean room air
- Method of conditioning air: not reported
- System of generating particulates/aerosols: DeVilbiss No. 40 nebulizer
- Method of particle size determination: gravimetrical determination
- Treatment of exhaust air: not reported
- Temperature, humidity, pressure in air chamber: 21 to 24°C, 50 to 68% relative humidity


TEST ATMOSPHERE
- Brief description of analytical method used: not reported; appendix not provided
- Samples taken from breathing zone: no


TEST ATMOSPHERE
Mass median aerodynamic diameter was within the range of 2.1 to 2.4 micrometres and geometric standard deviation was 1.63 to 1.77.
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
Nominal concentrations of 0, 2.5, 3.5, 5.0, 6.25, and 7.5 mg/L
Measured (time-weighted average) concentrations of 0, 2.34, 3.47, 5.06, 6.34 and 7.29 mg/L
No. of animals per sex per dose:
5 animals per sex per dose
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: All animals were checked twice daily for mortality. Animals were weighed prior to exposure and at days 7 and 14. Observation during exposure could not be completed due to decreased visibility as a result of aerosol production.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: lungs and any other grossly abnormal tissues were removed and fixed for histological examination.
Statistics:
Litchfield and Wilcoxon method was used to determine the LC50 value for the male data and the combined male and female data. Female data could not be fitted.

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LC50
Effect level:
4.65 mg/L air
95% CL:
3.89 - 5.55
Exp. duration:
4 h
Sex:
male
Dose descriptor:
LC50
Effect level:
4.65 mg/L air
95% CL:
4.22 - 5.13
Exp. duration:
4 h
Mortality:
In males, mortality was observed in 0 of 5, 1 of 5, 0 of 5, 3 of 5, 3 of 5, and 5 of 5 rats at measured exposures of 0, 2.34, 3.47, 5.06, 6.34, and 7.29 mg/L, respectively. In females, mortality was observed in 0 of 5, 0 of 5, 1 of 5, 1 of 5, 5 of 5, and 5 of 5 animals at the measured exposures of 0, 2.34, 3.47, 5.06, 6.34, and 7.29 mg/L, respectively. These deaths occurred during the 14-day observation period and not during the course of the 4-hour exposure.
Clinical signs:
other: Animals displayed hair coat abnormalities (oily/wetness), crust around nose at 2 to 4 days post-exposure, skin abnormalities (scabs/flaky), hair loss, urine stain on coat, decreased activity/mobility, and eye abnormalities.
Body weight:
A dose-related suppression in the body weight gain was observed on day 7 and in animals surviving until the end of the 14-day observation period, especially males.
Gross pathology:
At necropsy, observations included dark red lungs and blood stains around nose and on coats in phase 1 animals. In four animals that died, congestion and oedema with extravasation of red blood cells were observed. Additionally, spotty necrosis of the bronchiolar epithelium was noted. Interstitial inflammation, focal alveolar histocytosis, and localised emphysema were noted in phase 2 animals. The histologic changes in animals that died were considered to be severe enough to have been the cause of death.

Any other information on results incl. tables

Table 1. Mean body weight data expressed as a percentage of day 0 weight.

Phase and Group Number Measured Concentration Time-Weighted Average (mg/L) Male Female
Day 7 Day 14 Day 7 Day 14
PII-G1  0 111.2 120.4 107.0 113.2
PII-G2  2.34 99.6 113.4 105.2 108.4
PII-G4  3.47 100.4 111.4 100.1 105.8
PI-G1  5.06 99.7 116.4 99.3 111.5
PII-G5  6.34 92.1 103.2 - -
PII-G3  7.29 - - - -

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 4.65 mg/L in males and females. 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 COBS (CD) BR rats were exposed by inhalation route to light catalytically cracked distillate aerosol for 4 hours via whole-body exposure at measured concentrations of 0, 2.34, 3.47, 5.06, 6.34, or 7.29 mg/L.  Animals then were observed for 14 days.

There were no deaths during the exposure period in any of the investigations, 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. Decreased activity and mobility was reported at concentrations of 3.47 mg/L or 6.34 mg/L but not in male rats at 7.29 mg/L or either sex at 5.06 mg/L. During the observation period, mortality was observed in 0 of 5, 1 of 5, 0 of 5, 3 of 5, 3 of 5, and 5 of 5 male rats at measured exposures of 0, 2.34, 3.47, 5.06, 6.34, and 7.29 mg/L, respectively. In females, mortality was observed in 0 of 5, 0 of 5, 1 of 5, 1 of 5, 5 of 5, and 5 of 5 animals at the measured exposures of 0, 2.34, 3.47, 5.06, 6.34, and 7.29 mg/L, respectively. The inhalation LC50 was determined to be 4.65 mg/L (95% C.I.: 3.89 to 5.55 mg/L) in males and females, and 4.65 mg/L (95% C.I.: 4.22 to 5.13 mg/L) in males. The test material is classified as harmful by inhalation according to EU criteria.

This study received a Klimisch score of 1 and is classified as reliable without restriction because it closely followed OECD guideline 403.