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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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Near-guideline, GLP-compliant study. Adequate for assessment.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1987
Report Date:
1987

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
EPA OTS 798.1150 (Acute inhalation toxicity)
Principles of method if other than guideline:
Groups of young male and female rats SD were exposed (whole body) to aerosolised test substance for 4 h, followed by observation and gross necropsy on study day 14. The concentration of test substance within the chamber was determined by gravimetric calculation and particle size distribution by gravity impaction.
GLP compliance:
yes
Test type:
standard acute method

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: viscous hydrocarbon liquid
Details on test material:
Name of test material (as cited in Sponsor documentation): F-74-01, carbon black oil
- Liquid
- Density 0.9929 g/ml

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: 8-9 wk
- Body weight: males 240-330 g; females 210-240 g

IN-LIFE DATES: From: not stated To: 6-16 June 1986 (groups begun and terminated at different times)

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
whole body
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Plexiglass exposure chamber
- Exposure chamber volume: 100 l
- System of generating particulates/aerosols: Laskin 2 barrel Nebulizer
- Determination of exposure concentration: Whatman gravimetric glass microfibre filter paper + Millipore gravimetric filter holder
- Method of particle size determination: TS1 Aerodynamic Particle Sizer equipped with a TS1 Diluter
Analytical verification of test atmosphere concentrations:
yes
Remarks:
gravimetric
Duration of exposure:
4 h
Concentrations:
2100, 3300, 4800 mg/m3
No. of animals per sex per dose:
10 male, 10 female
Control animals:
no
Details on study design:
Groups of 10 male and 10 female Sprague-Dawley rats was exposed whole body to a mean analysed concentrations of 2100, 3300, 4800 mg/m3 F-74-01 aerosol. All survivors were held for a 14-day observation period after which a gross necropsy examination was conducted.

The 100 l exposure chambers were operated dynamically at a calibrated airflow rate of 15 l/min, calculated to provide one complete air change every 6.7 minutes and a 99% equilibrium time of 31 min. The test substance was heated then aerosolised using a Laskin 2 barrel Nebulizer and introduced into the chamber.

The exposure concentration was quantified using Whatman gravimetric glass microfibre filter paper (Type GF/F, 3.7 cm) mounted in a Millipore gravimetric filter holder (1.5 min sample time, flow rate 8.2 l/min) once per hour.

Particle size distribution measurements were made hourly using a TS1 Aerodynamic Particle Sizer (Model #3300) equipped with a TS1 Diluter (Model #3302). Particle size distribution was by computer-based analysis of the amount of material collected by the diluter.

Results and discussion

Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LC50
Effect level:
4 100 mg/m³ air (analytical)
95% CL:
1 500 - 11 000
Exp. duration:
4 h
Sex:
female
Dose descriptor:
LC50
Effect level:
4 500 mg/m³ air (analytical)
95% CL:
3 800 - 5 300
Exp. duration:
4 h
Sex:
male/female
Dose descriptor:
LC50
Effect level:
4 100 mg/m³ air (analytical)
95% CL:
2 100 - 7 900
Exp. duration:
4 h
Mortality:
Yes: 15/20 high dose animals died on or before study day 4 (no mortality in other groups).
Clinical signs:
other: Laboured breathing, nasal discharge and discoloured fur (head and body) in all groups during and up to 4 hr post-exposure.
Body weight:
Body weights for survivors were unremarkable.
Gross pathology:
Red mottling of the lungs and other organs recorded during necropsy was considered by the study pathologist to reflect pooling of blood in non-exsanguinated animals rather than a treatment-related phenomenon.

Applicant's summary and conclusion

Interpretation of results:
harmful
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Acute inhalation LC50 (aerosol, 4 hr) = 4100 mg/m3
Executive summary:

Groups of 10 male and 10 female SD rats were exposed to aerosolised test substance (2100, 3300 or 4800 mg/m3) for 4 hr, followed by a 14 day observation period.

Fifteen of twenty high dose animals died before study day 4 however no obviously treatment-related gross necropsy findings were apparent.

The acute inhalation LC50 of F-74-01 was 4100 to 4500 mg/m3.