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Description of key information

Male and female Tif. RAI rats were subjected to test acute oral toxicity. The test substance was administered by gavage at dose levels up to the highest applicable dose of 10000 mg/kg bw. No animal died under these conditions, thus leading to a LD50 > 10000 mg/kg bw. No substance related gross organ changes were seen at necropsy.

Acute inhalation toxicity of the test item has been investigated in male and female Tif: RAIf (SPF) rats (10 per sex). They were exposed to 4250 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 > 4250 mg/m³ (4.25 mg/L) for the inhalation of aerosol.

Acute dermal toxicity of the test item was tested in male and female Sprague-Dawley rats. The maximal applicable dose (3 g test item /kg bw suspended in polyethylene glycol:water 50:50 - final volume 9.9 ml; corresponding to 1710 mg/kg bw) were applied to the skin. No clinical signs were observed and no animals died during the 7 day observation period, resulting in a LD50 > 3000 mg/kg bw (corresponding to > 1710 mg/kg bw).

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1973
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study with acceptable restrictions (e.g. only 7 days post observation period, no details on body weight development)
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
: only 7 days of observation p.a.; details on body weight development are missing
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
other: Tif. RAI
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: SPF in-house breeding colony
- Age at study initiation: 6 to 7 weeks
- Weight at study initiation: 160 to 180g
- Fasting period before study: one night before treatment
- Housing: caged in Macrolon cages (type 3) in groups of five (male and female separately)
- Diet: ad libitum
- Water: ad libitum
Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 50% suspension in 2% CMC

Doses:
6000 and 10000 mg/kg
No. of animals per sex per dose:
5
Control animals:
no
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 10 000 mg/kg bw
Remarks on result:
other: no animals died within the observation period

- within 2 hours after treatment, all treated animals showed dyspnoea, exophthalmus, curved position and ruffled fur

- in the higher dose (10 g/kg bw) these symptoms became more accentuated

- all animals recovered within 3 to 6 days

- animals were sacrificed at day 7, but no substance related gross organ changes were seen

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: other: CLP regulation
Conclusions:
Single application of different dose levels ( up to 10 g/kg bw) of the test substance did not cause lethality in male and female Tif. RAI rats during the 7 day observation period, resulting in a LD50 > 10000 mg/kg bw.
Executive summary:

Male and female Tif. RAI rats were subjected to test acute oral toxicity. The test substance was administered by gavage at dose levels up to the highest applicable dose of 10000 mg/kg bw. No animal died under these conditions, thus leading to a LD50 > 10000 mg/kg bw. No substance related gross organ changes were seen at necropsy.

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

Endpoint:
acute toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
Please, see read across document in chapter 13
Reason / purpose for cross-reference:
read-across source
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 10 000 mg/kg bw
Remarks on result:
other: no animals died within the observation period
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: other: CLP regulation
Conclusions:
Single application of different dose levels ( up to 10 g/kg bw) of the test substance did not cause lethality in male and female Tif. RAI rats during the 7 day observation period, resulting in a LD50 > 10000 mg/kg bw.
Executive summary:

Male and female Tif. RAI rats were subjected to test acute oral toxicity. The test substance was administered by gavage at dose levels up to the highest applicable dose of 10000 mg/kg bw. No animal died under these conditions, thus leading to a LD50 > 10000 mg/kg bw. No substance related gross organ changes were seen at necropsy.

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:
LD0
Value:
> 2 000 mg/kg bw
Quality of whole database:
reliable with restriction: read across

Acute toxicity: via inhalation route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1978
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
: 10 hrs light cycle, some exposure data are missing (e.g. MMAD (not calculated), equilibration period)
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Tif: RAIf (SPF)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: in house breeding, SPF breeding colony
- Weight at study initiation: 170 - 190 g
- Housing: in Macrolon cages (type 4) in groups of 10, males and females separated
- Diet: NAFAG (Gossau SG, Switzerland), ad libitum
- Water: ad libitum
- Acclimation period: at least 4 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/-1
- Humidity (%): 55+/-5
- Photoperiod: 10 hrs light cycle day
Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: inhalation cylinder
- Method of holding animals in test chamber: seperate PVC tubes
- System of generating aerosols: Injecting the solid material with the help of "Grafix Exactometer injector" into an air stream which was discharged into the exposure chamber through a nozzle under a pressure of 2 atm. at a rate of 20 L/min.
- Method of particle size determination: gravimetrically
- Temperature, humidity, oxygen: 24 °C, 38%, 20 Vol.%

TEST ATMOSPHERE
- Brief description of analytical method used: Concentration was determined gravimetrically by sampling the test atmosphere through a selectron filter of 50 mm diameter and with a pore size of 0.2 µm (Schleicher and Schuell, Feldbach, Switzerland) at an air flow rate of 10 L/min. The size distribution of the particles was measured with a Cascade Impactor with selectron filters of 25 mm diameter and with pore size of 0.2 µm (Schleicher and Schuell, Feldbach, Switzerland) at an air flow rate of 17.5 L/min.
- Samples taken from breathing zone: yes

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: < 1 µm to > 7 µm
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): not calculated
Analytical verification of test atmosphere concentrations:
yes
Remarks:
: gravimetric measurement
Duration of exposure:
4 h
Concentrations:
4250 (+/-128) mg/m³
No. of animals per sex per dose:
10
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 4 250 mg/m³ air (analytical)
Exp. duration:
4 h
Remarks on result:
other: no animals died within the 14 day observation period
Mortality:
- no death occurred
Clinical signs:
other: - within 3 to 4 hours after starting the exposure period rats showed dyspnoea, curved or ventral position and ruffled fur - recovery within 4 days
Gross pathology:
- no macroscopically visible changes were found
Interpretation of results:
GHS criteria not met
Conclusions:
Exposure of male and female rats to 4250 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 > 4250 mg/m³.
Executive summary:

Acute inhalation toxicity of the test item has been investigated in male and female Tif: RAIf (SPF) rats (10 per sex). They were exposed to 4250 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 > 4250 mg/m³ (4.25 mg/L) for the inhalation of aerosol.

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

Endpoint:
acute toxicity: inhalation
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
Please see read across justification document on Chapter 13

Reason / purpose for cross-reference:
read-across source
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 4 250 mg/m³ air (analytical)
Exp. duration:
4 h
Remarks on result:
other: no animals died within the 14 day observation period
Mortality:
- no death occurred
Interpretation of results:
GHS criteria not met
Conclusions:
Exposure of male and female rats to 4250 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 > 4250 mg/m³.
Executive summary:

Acute inhalation toxicity of the test item has been investigated in male and female Tif: RAIf (SPF) rats (10 per sex). They were exposed to 4250 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 > 4250 mg/m³ (4.25 mg/L) for the inhalation of aerosol.

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

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Physical form:
inhalation: dust / mist
Quality of whole database:
reliable with restriction: read across

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
reliable with restriction: read across

Additional information

Justification for classification or non-classification

No classification

No adverse effects were observed after acute oral d3eremal or inhalation exposure.