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Administrative data

Description of key information

Acute toxicity after single oral application was tested in female rats, which received up to 5000 mg/kg bw (groups of ten females). The LD50value for acute oral toxicity is 2800 mg/kg bw. Gross pathology revealed darkly reddened/spotted lungs and liver in prematurely died animals. No changes were observed in surviving females.

 

A 4 h dust exposure of the test substance to 12 rats (6 males and 6 females) at concentrations of 444, 1006, 1228, 3005 or 8569 mg/m3led to a LC50was determined to be 1670 mg/m3(corresponding to 1.67 mg/L).

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
19. March - 2. May 1979
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Reference:
Composition 1
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
only females tested
GLP compliance:
no
Remarks:
performed before GLP implementation
Test type:
standard acute method
Limit test:
no
Test material information:
Composition 1
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Hoechst AG
- Females (if applicable) nulliparous and non-pregnant: yes
- Weight at study initiation: 160-184 g
- Fasting period before study: yes, 16 h
- Housing: in groups in plastic cages, softwood pellets
- Diet (e.g. ad libitum): Altromin 1324 (Altromin GmbH, Lage/Lippe), ad libitum
- Water (e.g. ad libitum): Tap water ad libitum

IN-LIFE DATES: From: 19.3. To: 2.5.1979
Route of administration:
oral: gavage
Vehicle:
other: 25% test substance in 2% starch suspension
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 25%
- Amount of vehicle (if gavage): 0.6 - 3.6 mL per animal


Doses:
1000, 3000 and 5000 mg/kg bw
No. of animals per sex per dose:
10 females/group
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily observation for mortality/clinical signs, weekly weighing
- Necropsy of survivors performed: yes
Statistics:
LD50 calculation by Probitanalysis according to Linder and Weber
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
2 800 mg/kg bw
Based on:
act. ingr.
95% CL:
1 520 - 3 670
Mortality:
1000 mg/kg bw: 0/10
3000 mg/kg bw: 6/10
5000 mg/kg bw: 9/10
Clinical signs:
hunchd posture, increased breathing rate, tremor; all symptoms were reversible within 24 h
Body weight:
no effects observed
Gross pathology:
Survivors: no changes
Descedents: darkly reddened/spotted lungs and liver
Interpretation of results:
Category 5 based on GHS criteria
Conclusions:
The median lethal dose of the testsubstance was 2800 mg per kg body weight. Based on the result of this study the test substance is acutely oral toxic, Cat 5.
Executive summary:

The test item was tested for its acute oral toxicity potential. 10 female rats were treated with doses of 1000, 3000, or 5000 mg/kg bw and observed for 14 days. The median lethal dose was 2800 mg per kg body weight. Based on the result of this study the test substance is acutely oral toxic, Cat 5 according to GHS criteria.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
2 800 mg/kg bw
Quality of whole database:
reliable with restrictions

Acute toxicity: via inhalation route

Link to relevant study records
Reference
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
Reference:
Composition 1
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 information:
Composition 1
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
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
Preliminary study:
not mentioned in the report
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.
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.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LC50
1.67 mg/m³
Quality of whole database:
reliable with restrictions

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
the study need not be conducted because skin contact in production and/or use is not likely
the study need not be conducted because the physicochemical and toxicological properties suggest no potential for a significant rate of absorption through the skin
Justification for type of information:
Due to REACH Regulation, Annex VIII, 8.5, the performance of a third acute toxicity test beyond the already tested oral and inhalation route is not mandatory.
Furthermore, it can reasonably be deduced that 2,2,4,4-Tetramethyl-7-oxa-3,20-diazadispiro[5.1.11.2]-henicosan-21-one does not exert systemic toxic effects after dermal application and thus does not have to be classified, because the oral LD50 derived for this substance is greater than 2,000 mg/kg bw in female rats. Furthermore the substance does not have to be classified as skin irritating. Due to its molecular structure it is unlikely that higher amounts (limit dose of dermal toxicity testing according OECD 402: 2,000 mg/kg bw/d) than tested in the acute oral toxicity study (tested up to 5,000 mg/kg bw/d) will be systemically available via the intact skin barrier even if the most unlikely amount of 100% penetration is assumed. Therefore, testing is not scientifically necessary.
Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

none

Justification for classification or non-classification

Due to the results described in the acute oral and inhalation toxicity studies (LD50oral 2800 mg/kg bw; LC50 1.67 mg/L) the substance has to be classified as acute orally toxic Cat. 5 and toxic via the inhalation route Cat. 4. Based on the substance's physico-chemical properties no higher systemically exposure via dermal penetration is expected to occur than that tested in the course of the oral toxicity study. Therefore, test item does not have to be classified as acute dermally toxic.