Registration Dossier

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1980
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well-documented study which meets basic scientific principles

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1980
Report Date:
1980

Materials and methods

Principles of method if other than guideline:
4 hour inhalation, 5 male, 5 female, Sprague-Dawley rats
GLP compliance:
not specified
Test type:
fixed concentration procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): C-194
- Physical state: solid
- Analytical purity: 100%

Comment by the applicant:
Existing retained samples from batches of C-194 of 1980 were analytically rechecked. The identity was confirmed with a content of 4-HBA of approximately 100% (NMR analysis).

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories, Wilmington, Massachusetts
- Weight at study initiation: males: 240-297g, females: 218-237g
- Fasting period before study: no

Administration / exposure

Route of administration:
inhalation: dust
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
- Source and rate of air: dry air, flow rate 15 l per minute
- Method of conditioning air: Wright Dust Feeder
- Method of particle size determination: Casella Cascade Impactor

TEST ATMOSPHERE (if not tabulated)
- Nominal concentration: 7.91 mg/l
- Particle size distribution: average mass median diameter = 5.8µm +-2.3-3.3
- mean airborne concentration: 0.47 mg/l
- Temperature: 22 °C
- Mean relative humidity: 88%
Analytical verification of test atmosphere concentrations:
no
Duration of exposure:
4 h
Concentrations:
7.91 mg/l
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations (during exposure): before exposure, every 15 minutes during the first hour of exposure and hourly through termination
- Frequency of observations: hourly for 4 hours post-exposure
- Frequency of weighing: day 0 (prior to exposure), 1, 2, 4, 7, and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross necropsy examination

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
discriminating conc.
Effect level:
>= 0.47 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: effects of irritation of the inner surfaces of the respiratory tract observed, nominal concentration: 7.91 mg/L
Mortality:
no
Clinical signs:
other: Fur contaminated with test material, reduced activity, wet and/or matted fur, excessive salivation, rapid breathing, stained fur, mucoid nasal discharge, dried material around eyes, nose, mouth, walking on toes, body tremors, lack of grip, transient weig
Body weight:
weight losses in all male rats, body weight and body weight gain in the second week within the expectations
Gross pathology:
5 male and 3 female showed foci and areas of lung discoloration (no histopathology).

Any other information on results incl. tables

Nominal concentration in the air: 7.91 mg/L.

Mean airborne testmaterial concentration: 0.47 mg/l,

Chamber distribution: at the inlet portal: 0.48 mg/L, at the outlet portal: 0.43 mg/L,

Average aerodynamic mass median diameter: 5.8 µm, standard deviation: 2.3 to 3.3 µm.

Chamber temperature: 22°C

Mean relative humidity: 88%.

Applicant's summary and conclusion

Executive summary:

A 4 hour inhalation exposure to a dust of 4 -HBA at a nominal concentration of 7.91 mg/l (7910 mg/m³) with an aerodynamic mass median diameter of 5.8 micrometers with a geometric standard deviation range of 2.3 to 3.3 and a mean airborne concentration of 0.47 mg/l (470 mg/m³) did not produce mortality. The following test item related clinical symptoms were observed:

fur contaminated with test material, reduced activity, wet and/or matted fur, excessive salivation, rapid breathing, stained fur, mucoid nasal discharge, dried material around eyes, nose, mouth, walking on toes, body tremors, lack of grip, transient weight loses in male rats. During the 14 -day observation period persistent dry slight rales were observed predominantly in male rats.

At necropsy, 5 male and 3 female rats showed foci and areas of lung discoloration.