2,2,4,4-tetramethyl-7-oxa-3,20-diazadispiro[5.1.11.2]-henicosan-21-one

Acute Toxicity: inhalation

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

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

Test material information

Constituent 1

Reference substance name:

Hostavin TM N20

IUPAC Name:

Hostavin TM N20

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 or test system 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:

other: 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 p

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.