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Description of key information

Female rats were subjected to test acute oral toxicity. The test substance was administered by gavage at the highest applicable dose of 15000 mg/kg bw. Three animals died at this dose within 4 hours after application showing no signs of toxicity. The other animals survived the 14 day observation period. At the end of the observation period there were no changes found in necropsy in all animals. Due to this findings the oral LD50 value is > 15000 mg/kg bw.

Acute inhalation toxicity of the test item has been investigated in male and female Wistar rats. They were exposed to 230 mg test substance per cubic meter for 4 h (maximal applicable dose). All animals survived the 14 day observation period. No macroscopic visible changes were observed at necropsy at the end of the observation period, resulting in a LC50 value of > 230 mg/m³ for the inhalation of dust.

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:
From 24 SEP 1974 to 8 OCT 1974
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Basic data given: comparable to guidelines
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
not applicable
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: SPF breeding colony
- Weight at study initiation: mean 91 g
- Fasting period before study: 16 h
- Housing: plastic cages
- Diet: Altromin 1324 (Altromin GmbH, Lage/Lippe, Germany), ad libitum
- Water: tap water, ad libitum
Route of administration:
oral: gavage
Vehicle:
other: sesame oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 25% suspension in vehicle
Doses:
15000 mg/kg bw
No. of animals per sex per dose:
10
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of weighing: weekly
- Necropsy of survivors performed: yes
Sex:
female
Dose descriptor:
LD50
Effect level:
> 15 000 mg/kg bw
Remarks on result:
other: 3 animals died within 175 to 245 minutes post application without any visible signs of toxicity
Mortality:
- 3 animals died within 175 to 245 min after the application
- the remaining 7 animals survived the observation period
Clinical signs:
other: - faeces and urine were yellow-coloured
Gross pathology:
- the deceased animals during the test as well as the animals killed at the end of the observation period showed no macroscopically visible changes
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: other: CLP regulation
Conclusions:
The testing for acute oral toxicity yielded a median lethal dose (LD50) of > 15000 mg test substance per kg bw in female rats.
Executive summary:

Female rats were subjected to test acute oral toxicity. The test substance was administered by gavage at the highest applicable dose of 15000 mg/kg bw. Three animals died at this dose within 4 hours after application showing no signs of toxicity. The other animals survived the 14 day observation period. At the end of the observation period there were no changes found in necropsy in all animals. Due to this findings the oral LD50 value is > 15000 mg/kg bw.

Classification for acute oral toxicity is not necessary according to Regulation (EC) No 1272/2008 .

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
> 15 000 mg/kg bw
Quality of whole database:
reliable

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:
From 4 DEC 1989 to 18 DEC 1989
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study (OECD TG 403)
Reason / purpose for cross-reference:
reference to same study
Qualifier:
according to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.2 (Acute Toxicity (Inhalation))
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Hoechst AG, Kastengrund, SPF breeding colony
- Age at study initiation: 8 to 10 weeks
- Weight at study initiation: males mean: 227 g; females mean: 195 g
- Housing: macrolon cages (type 4) groups of 5 respectively 2 (= control animal and animal killed 1 day post application)
- Diet: rat diet Altromin 1324 ( Altromin-GmbH, Lage/Lippe, Germany); ad libitum
- Water: Tap water; ad libitum
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/- 2
- Humidity (%): 50 +/- 20
- Photoperiod (hrs dark / hrs light): 12/12


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: cylindrical plastic cage
- Exposure chamber volume: 60 L
- Method of holding animals in test chamber: each animal was in a plastic tube
- Source and rate of air: laminar air stream of 1000 L/hour at 4 bar from above
- System of generating particulates/aerosols: dustgenerator "Wright Dust Feed" of L. Adams Ltd., London, UK
- Method of particle size determination: "Anderson-Kaskadenimpaktor Mark III" of Anderson Samples Inc, Atlanta, USA
- Treatment of exhaust air: exhaust device at the basement of the exposure chamber in line with a diverse system of filters

TEST ATMOSPHERE ANALYSIS
- Brief description of analytical method used: gravimetric measurement: The test atmosphere was sucked through filters ("Experimentiertrommelgasfilter", Elster AG, Mainz-Kastel, Germany; as well as a fibre glass and a membrane filter (diameter of pores 0.65 µm) Satorius Membranfilter GmbH, Göttingen, Germany) by means of vacuum. The exhaust quantity was 3 L/min, which resulted in an air flow of 1.25 m/sec. The filters were positioned in an exsiccator 24 h before use. The filters were weighed before and after each measurement by means of electrical scales.

TEST ATMOSPHERE
- Particle size distribution: < 0.6 µm to > 10.3 µm
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): 1.0 - 1.1/ 2.3 - 2.8
Analytical verification of test atmosphere concentrations:
yes
Remarks:
gravimetric measurement
Duration of exposure:
4 h
Concentrations:
230 mg/m³ air
No. of animals per sex per dose:
6/sex/treatment group
1/sex/control group
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: twice a day
- Frequency of weighing: weekly
- Necropsy of survivors performed: yes

- Control urine and blood samples were collected from control animals.
- On day 1, 2 and 7 one male and one female were sacrificed to obtain blood samples. Final sacrifice of the remaining 3 animals/sex was on day 14 of the observation period.
- Urin samples were collected starting on the day of exposure till day 7 of the observation period and the last night before sacrifice.
- To collect urine the rats were placed in metabolism cages overnight without witdrawal of food and water. For technical reasons urine was collected continously on day 6 and 7.
- Blood was collected via puncture of the retro-orbital plexus.
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 230 mg/m³ air
Exp. duration:
4 h
Remarks on result:
other: no animals died within the 14 day observation period
Mortality:
- no deaths occurred
Clinical signs:
other: - during the exposition: irregular breathing, narrowed palpebral fissures and female animals showed additional stilted gate - no more clinical signs were observed in males 330 minutes p.a. and in females 450 minutes p.a.
Body weight:
- Body weight development was impaired in the first week, probably due to the frequent placement in metabolism cages.
- But all animals except for one female did excess their initial body weight at the end of the test period.
Gross pathology:
- no macroscopically visible changes were found
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: other: CLP regulation
Conclusions:
Exposure of male and female Wistar rats to 230 mg/m³ test item for 4 hours did not result in the death of the animals during a 14 day observation period, resulting in a LC50 value of > 230 mg/m³.
Executive summary:

Acute inhalation toxicity of the test item has been investigated in male and female Wistar rats. They were exposed to 230 mg test substance per cubic meter for 4 h (maximal applicable dose). All animals survived the 14 day observation period. No macroscopic visible changes were observed at necropsy at the end of the observation period, resulting in a LC50 value of > 230 mg/m³ for the inhalation of dust.

Classification for acute inhalation toxicity is not necessary according to Regulation (EC) No 1272/2008 .

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC0
Value:
> 230 mg/m³ air
Physical form:
inhalation: aerosol
Quality of whole database:
reliable

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification

No classification

Neither oral nor inhalation exposure caused adverse effects in rats at the maximum technical doses