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Administrative data

Description of key information

The key acute oral toxicity study for the submission substance, conducted according to an appropriate OECD test guideline and in compliance with GLP, reported an LD50 value of greater than 2000 mg/kg bw (RCC 2004).

The key acute dermal toxicity study for the submission substance, conducted according to an appropriate OECD test guideline and in compliance with GLP, reported an LD50 value of greater than 2000 mg/kg bw (RCC 2004).

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:
09 June 2004 to 02 July 2004
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
2001
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Version / remarks:
1996
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes
Specific details on test material used for the study:
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: at room temperature, light protected
- Stability under test conditions: stable under storage conditions
- Solubility and stability of the test substance in the solvent/vehicle: stable in corn oil
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium: not applicable

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: The test material was diluted in corn oil. The dose formulations were made shortly before each dosing occasion using a magnetic stirrer. Homogeneity of the test item in the vehicle was maintained during administration using a magnetic stirrer.
- Preliminary purification step (if any): none
- Final dilution of a dissolved solid, stock liquid or gel: not applicable
- Final preparation of a solid: not applicable



Species:
rat
Strain:
Wistar
Remarks:
HanBrl: Wist (SPF)
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: RCC Ltd., Laboratory Animal Services, Switzerland
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 12 weeks
- Weight at study initiation: not specified
- Fasting period before study: 18 hours
- Housing: In group of three in Makrolon type-4 cages with wire mesh and tops and standard softwood bedding.
- Diet: Pelleted standard Provimi Kliba 3433 rat/mouse maintenance diet, ad libitum
- Water: Community tap water, ad libitum
- Acclimation period: Yes. Under laboratory conditions, after health examination.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/-3°C
- Humidity (%): 30-70 %
- Air changes (per hour): 10-15 air changes per hour
- Photoperiod (hours dark / hours light): 12/12
Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 0.02 g/mL
- Amount of vehicle (if gavage): not specified
- Justification for choice of vehicle: Corn oil was found to be a suitable vehicle. The vehicle was chosen after a non-GLP solubility trial which was performed before the study initiation date.
- Lot/batch no. (if required): 45256503
- Purity: not specified

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

DOSAGE PREPARATION (if unusual): The test material was diluted in corn oil. The dose formulations were made shortly before each dosing occasion using a magnetic stirrer. Homogeneity of the test item in the vehicle was maintained during administration using a magnetic stirrer.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: starting dose was 2000 mg/kg bw in accordance with the test method.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed for clinical signs of toxicity at approximately 1, 2, 3 and 5 hours after administration on test day 1 and twice daily during days 2-15. Animals were weighed on test days1, 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
Not used
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths occurred during the study.
Clinical signs:
Slightly ruffled fur was noted in two animals at the 1-hour reading and persisted up to the 3-hour reading in one animal.
Body weight:
The body weight of the animals was within the range commonly recorded for this strain and age.
Gross pathology:
No macroscopic findings were recorded at necropsy.
Other findings:
- Organ weights: not examined
- Histopathology: not examined
- Potential target organs: not examined
Interpretation of results:
GHS criteria not met
Conclusions:
The acute oral toxicity study for the submission substance, conducted according to an appropriate OECD test guideline and in compliance with GLP, reported an LD50 value of greater than 2000 mg/kg bw.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
09 June 2004 to 30 June 2004
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
1987
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
1992
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes
Specific details on test material used for the study:
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: at room temperature, protected from light
- Stability under test conditions: stable under test conditions
- Solubility and stability of the test substance in the solvent/vehicle: not applicable
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium: not applicable

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: The test material was applied undiluted.
- Preliminary purification step (if any): none
- Final dilution of a dissolved solid, stock liquid or gel: not applicable
- Final preparation of a solid: not applicable
Species:
rat
Strain:
Wistar
Remarks:
HanBrl: WISR (SPF)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: RCC Ltd, Laboratory Animal Services, Switzerland
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: males 8 weeks; females 12 weeks old
- Weight at study initiation: not specified
- Fasting period before study: none
- Housing: During acclimatisation in groups of five per sex in Makrolon type-4 cages with standard softwood bedding. Individually in Makrolon type-3 cages with standard softwood bedding during treatment and observation.
- Diet: Pelleted standard Provimi Kliba 3433 rat/mouse maintenance diet, ad libitum
- Water: Community tap water, ad libitum
- Acclimation period: Under laboratory conditions, after health examination. Only animals without any visible signs of illness were used for the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/-3°C
- Humidity (%): 30-70%
- Air changes (per hour): 10-15 air changes per hour
- Photoperiod (hours dark / hours light): 12/12

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: backs of the animals
- % coverage: 10% of body surface
- Type of wrap if used: The dressing was wrapped around the abdomen and fixed with an elastic adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Approximately 24 hours after the application the dressing was removed and the skin was flushed with lukewarm tap water and dried with disposable paper towels.
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.02 mL
- Concentration (if solution): not applicable
- Constant volume or concentration used: yes
- For solids, paste formed: not applicable

VEHICLE
The test item was applied undiluted.
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: The animals were observed for mortality and viability at approximately 1, 2, 3 and 5 hours after administration on test day 1 and twice daily during days 2-15. Body weights were recorded on test days 1, 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs and body weight
Statistics:
Not used
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths occurred during the study.
Clinical signs:
No signs of systemic toxicity were observed during the study period. Slight crusts were noted in one female animal on test days 14 and 15.
Body weight:
The body weight of the animals was within the range commonly recorded for this strain and age.
Gross pathology:
No macroscopic findings were observed at necropsy.
Other findings:
- Organ weights: not examined
- Histopathology: not examined
- Potential target organs: not examined
- Other observations:
Interpretation of results:
GHS criteria not met
Conclusions:
The acute dermal toxicity study for the submission substance, conducted according to an appropriate OECD test guideline and in compliance with GLP, reported an LD50 value of greater than 2000 mg/kg bw.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Additional information

The key acute oral toxicity study for the submission substance, conducted according to an appropriate OECD test guideline and in compliance with GLP, reported an LD50 value of greater than 2000 mg/kg bw (RCC, 2004).

Following single oral gavage administration of 2000 mg/kg bw test substance in corn oil to female rats, no mortality was observed in any of the test animals during the 14-day study period. Slightly ruffled fur was noted in two animals at 1-hour reading and persisted up to 3-hour reading in one animal. The body weight of the animals was within the range commonly recorded for this strain and age. No macroscopic findings were recorded at necropsy.

The key acute dermal toxicity study for the submission substance, conducted according to an appropriate OECD test guideline and in compliance with GLP, reported an LD50 value of greater than 2000 mg/kg bw (RCC, 2004).

Following single dermal application of 2000 mg/kg bw undiluted test substance to male and female rats for 24 hours under semi-occlusive dressing, no mortality was observed in any of the test animals during the 15-day study period. No systemic signs of toxicity were observed in any of the test animals. Slight crusts were noted in one female animal on test days 14 and 15. The body weight of the animals was within the range commonly recorded for this strain and age. No macroscopic findings were recorded at necropsy.

Justification for classification or non-classification

Based on the available data for the submission substance, no classification is required for acute toxicity according to Regulation (EC) No 1272/2008.