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Description of key information

In an acute oral toxicity study in female rats, conducted in accordance with OECD 423 (2001) and according to GLP principles, a LD50 of >2000 mg/kg bw was determined. In an acute dermal toxicity study with rats, performed in accordance with OECD 402 (1987) and according to GLP principles, a LD50 of >2000 mg/kg bw was determined.

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:
August 23, 2006 - November 14, 2006
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This study has been performed in accordance with OECD 423 (2001) and according to GLP principles.
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
(2001)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals or test system and environmental conditions:
- Source: Harlan Winkelmann GmbH, Gartenstrasse 27, 33178 Borchen, Germany
- Age at study initiation: no data
- Weight at study initiation:
Group 1: 194-211 g (mean: 203.67 g)
Group 2: 182-195 g (mean: 186.67 g)
- Body weight variation: less than 20% of the mean weight
- Housing: individually in Makrolon cages
- Diet: SDS RM1 Nagerfutter, Withham Essex, England. Twice 8 g daily.
- Water: Free access to tap water
- Acclimation period: 5 days
- Fasting period before study: overnight before the day of administration

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 – 25
- Humidity (%): 30 - 70
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
water
Remarks:
(1 mL)
Details on oral exposure:
DOSE VOLUME APPLIED:
Group 1: 389-422 mg/rat (dissolved in 1 mL water)
Group 2: 364-390 mg/rat (dissolved in 1 mL water)

DOSAGE PREPARATION:
Calculated amounts of the test material according to the dosage of 2000 mg/kg bw were dissolved in 1 mL water and administered to the rats in a single dose with the aid of a stomach tube.

Doses:
2000 mg/kg bw
No. of animals per sex per dose:
6 (2 groups of three females in a stepwise manner)
Control animals:
other: not required
Details on study design:
- Animals were deprived of food overnight prior to dosing and until 4 hours after administration of the test substance. Water was available ad libitum.
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality/Viability: daily
Body weights: daily
Clinical signs: At periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15.
- Necropsy of survivors performed: yes
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortalities and no clinical signs of toxicity occurred
Mortality:
Group 1: No mortalities occurred.
Group 2: No mortalities occurred.
Clinical signs:
other: No clinical signs of toxicity occurred in any of the animals.
Gross pathology:
Macroscopic examination of the animals did not reveal any abnormalities.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In an acute oral toxicity study in female rats with the substance, conducted in accordance with OECD 423 (2001) and according to GLP principles, a LD50 oral of >2000 mg/kg was determined.
Executive summary:

The acute oral toxicity of the substance in female rats has been studied in accordance with OECD 423 (2001) and according to GLP principles. The substance was dosed in water at 2 g/kg bw in 6 female rats, in 2 steps. No mortalities and no clinical signs of toxicity occurred in any of the animals. Necropsy did not show any abnormality. The acute oral toxicity (LD50) was determined to be >2000 mg/kg bw. Based on this result, the substance does not need to be classified for acute toxicity by the oral route.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
The study has a Klimisch score of 1.

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:
August 23, 2006 - November 14, 2006
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This study has been performed in accordance with OECD 402 (1987) and according to GLP principles.
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
(1987)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
- Source: Harlan Winkelmann GmbH, Gartenstrasse 27, 33178 Borchen, Germany
- Age at study initiation: no data
- Weight at study initiation: 201-220 g (mean weight: 208.8 g)
- Body weight variation: less than 20% of the mean weight
- Housing: individually in Makrolon cages
- Diet: SDS RM1 Nagerfutter, Withham Essex, England. Twice 8 g daily.
- Water: Free access to tap water
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 – 25
- Humidity (%): 30 - 70
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
occlusive
Vehicle:
other: moistened with water
Details on dermal exposure:
- 24 hours before exposure the dorsal area of the trunk was shaved in an area of approximately 10% of the body surface
- The dosage was applied onto gauze and moistened with water
- The gauze was applied onto the shaved area and was held in place with an occlusive bandage
- The bandage was fixed with 1.25 cm broad stripes of Adhesive tape.
- Frequency: Single dosage
- At the end of the exposure period residual test item was removed by gently washing with water
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw

No. of animals per sex per dose:
5
Control animals:
not required
Details on study design:
- Dose volume: 402-440 mg/rat
- Duration of observation period following administration (on day 1): 14 days
- Frequency of observations and weighing:
Mortality/Viability: daily
Body weights: daily
Clinical signs: At periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15.
- Necropsy of survivors performed: yes
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortalities and no clinical signs of toxicity occurred
Mortality:
No mortalities occurred.
Clinical signs:
other: No clinical signs of toxicity occurred in any of the animals.
Gross pathology:
Macroscopic examination of the animals did not reveal any abnormalities.
Other findings:
No erythema or oedema was observed during the observation period. Therefore this study does not indicate skin irritation.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In an acute dermal toxicity study with rats, performed in accordance with OECD 402 (1987) and according to GLP principles, a LD50 of >2000 mg/kg bw was determined for the substance.
Executive summary:

The acute dermal toxicity of the substance was determined in the rat, in accordance with OECD 402 (1987) and according to GLP principles. The substance was administered to five Sprague-Dawley rats of each sex by a single dermal application of 2000 mg/kg bw for 24 hours. No mortality and no clinical signs of toxicity occurred in any of the animals. Body weight determinations and macroscopic examination of the animals did not reveal any abnormalities. The dermal LD50 value of the substance in Sprague-Dawley rats was established to be >2000 mg/kg bw. Based on this result, the substance does not need to be classified for acute toxicity by the dermal route.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
The study has a Klimisch score of 1.

Additional information

Oral

The acute oral toxicity of the substance in female rats has been studied in accordance with OECD 423 (2001) and according to GLP principles. The substance was dosed in water at 2 g/kg bw in 6 female rats, in 2 steps. No mortalities and no clinical signs of toxicity occurred in any of the animals. Necropsy did not show any abnormality. The acute oral toxicity (LD50) was determined to be >2000 mg/kg bw.

Dermal

The acute dermal toxicity of the substance was determined in the rat, in accordance with OECD 402 (1987) and according to GLP principles. The substance was administered to five Sprague-Dawley rats of each sex by a single dermal application of 2000 mg/kg bw for 24 hours. No mortality and no clinical signs of toxicity occurred in any of the animals. Body weight determinations and macroscopic examination of the animals did not reveal any abnormalities. No erythema or oedema was observed during the observation period. The dermal LD50 value of the substance in Sprague-Dawley rats was established to be >2000 mg/kg bw.


Justification for selection of acute toxicity – oral endpoint
There is one study available.

Justification for selection of acute toxicity – dermal endpoint
There is one study available.

Justification for classification or non-classification

Based on the observed LD50 oral and dermal of >2000 mg/kg bw, the substance does not have to be classified for acute oral and dermal toxicity according to the CLP Regulation.