Registration Dossier

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1981
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Scientifically acceptable, OECD Guideline 403 conform with minor deviations, No GLP study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1981
Report Date:
1981

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Principles of method if other than guideline:
6 males and 6 females were used per dose group.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Hostavin TM N 20
- Physical state: powder
- Analytical purity: not known

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Females (if applicable) nulliparous and non-pregnant: yes
- Weight at study initiation: males: 172-200 g; females: 178-201 g
- Housing: in Makrolon cages
- Diet (e.g. ad libitum): Altromin 1324, ad libitum except during exposure to the test substance
- Water (e.g. ad libitum): tap water, ad libitum except during exposure to the test substance
- Acclimation period:



IN-LIFE DATES: From: 27. 07. To: 07.09.1981

Administration / exposure

Route of administration:
inhalation: dust
Type of inhalation exposure:
nose only
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Plastic pipes connected to the exposure chamber
- Exposure chamber volume: 60 l
- Source and rate of air: 1200 l/h
- System of generating particulates/aerosols: Using Dustgenerator, Wright Dust Feed Mechanism, L-Adams Ltd., London
- Method of particle size determination: Using Partikelzählsystem Modell 225, kratel Kg, Stuttgart
- Treatment of exhaust air: Filtering and via three neck bottle filled with water
- Temperature, humidity, pressure in air chamber: Monitored using a commercial air-monitoring system

TEST ATMOSPHERE
- Brief description of analytical method used: Gas chromatography
- Samples taken from breathing zone: no

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: 70% < 3 µm, 90% < 6 µm
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
ca. 4 h
Concentrations:
Group 1: 444 mg/m3
Group 2: 1006 mg/m3
Group 3: 1228 mg/m3
Group 4: 3005 mg/m3
Group 5: 8569 mg/m3
No. of animals per sex per dose:
6
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:daily obvervation and weekly weighing
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, macroscopic investigation upon necropsy

Results and discussion

Preliminary study:
not mentioned in the report
Effect levels
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
ca. 1 670 mg/m³ air (analytical)
95% CL:
> 1 310 - < 2 320
Exp. duration:
4 h
Mortality:
At concentration of 444 mg/m3: no deaths
At concentration of 1006 mg/m3: no deaths
At concentration of 1228 mg/m3: 2 males and 4 females (out of 6 males and 6 females) died within 4 days after treatment.
At concentration of 3005 mg/m3: 4 males and all females died within 8 days after treatment.
At concentration of 8569 mg/m3: all animals died either during or within 5 days after treatment.
Clinical signs:
In dose dependent manner following observations were present: narrowed palpebral fissure, irregular breathing, serous rhinorrhea, bloody encrusted stoma, gasping, rales, salivation, disturbance of equilibrium, tremor, hyporeflexia, haemolacria, hunched posture and abdomal position.
In dose dependent manner the clinical signs persisted until the end of the observation period.
Body weight:
The body weight development of the animals treated at concentration of 444 mg/m3 was not impared within the observation period of 14 days.
A body weight loss was observed for the animals treated at concentrations of 1006 mg/m3 and above and the body weight gain in the observation period was impaired in dose dependent manner.
Gross pathology:
In lungs of the dead animals dark red coloured herds and bloody foams were found.
Upon necropsy of the survived animals at the end of the observation period, no observation was made.

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
LC50 (4h): 1670 mg/m3 - 1.67 mg/L
Executive summary:

In order to investigate the acute inhalation toxicity rats were treated with the test substance via nose-only-inhalation at concentrations of 444, 1006, 1228, 3005 and 8569 mg/m3 for 4 hours. LC50 was determined to be 1670 mg/m3. In lungs of the dead animals dark red coloured herds and bloody foams were found. Toxic signs such as clinical symptoms, body weight loss and impairment of body weight gains were observed, partially until the end of the observation period of 21 days.