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Description of key information

In standard single-dose toxicity studies in rats the following results were obtained:

In an OECD401 study, the acute oral LD50 in rats was determined to be > 2000 mg/kg bodyweight.

In an OECD402 comparable study, the acute dermal LD50 in rats was determined to be >10000 mg/kg bodyweight

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:
29 March 1989 to 13 April 1989
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
1987
Deviations:
not specified
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Fü-albino SPF
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: Males about 6 weeks, females 6 to 7 weeks.
- Weight at study initiation: Males 125.0 to 132.7 g, females 125.0 to 140.6 g.
- Fasting period before study: About 18 hours.
- Housing: Individually caged.
- Diet: NAFAG standard rat maintenance diet, ad libitum.
- Water: Tap water, ad libitum.
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 24 °C
- Humidity (%): 45 to 65 %
- Photoperiod (hrs dark / hrs light): 12 hours artificial light, 12 hours darkness.
Route of administration:
oral: gavage
Vehicle:
other: Standard Suspending Vehicle (SSV)
Remarks:
1000 mL SSV contains 5 g sodium carboxy methyl cellulose (medium viscosity), 4 mL Tween 80, 5 mL benzylalcohol pro analysi, 9 g sodium-chloride pro analysi and distilled water.
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 2000 mg/kg
- Amount of vehicle (if gavage):

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg body weigth

DOSAGE PREPARATION: The test article was kept suspended in Standard Suspending Vehicle (SSV) using a homogeniser. Homogeneity of the test article in the vehicle was maintained during treatment using a magnetic stirrer.
Doses:
2000 mg/kg
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 16 days
- Frequency of observations and weighing: Mortality was recorded continuously and body weight was recorded on days 0 (immediately before treatment), 2, 6, 9, 13 and 15.
- Necropsy of survivors performed: Yes
- Other examinations performed: Behaviour, vivacity, signs of injury, signs of sickness and abnormality were performed repeatedly on the treatment day and daily during the treatment-free observation period.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
not determinable due to absence of adverse toxic effects
Mortality:
No deaths occurred.
Clinical signs:
No clinical signs were observed.
Body weight:
The body weight development of males and females took a normal course known for this species and age.
Gross pathology:
No autopsy findings were seen.

Table 1. Body weights

 Sex  Mean body weights in g (standard deviation)               
 n = 5  Day 0  Day 2  Day 6  Day 9  Day 13  Day 15
 Male  129.2 (2.8)  157.9 (4.2)  187.8 (6.2)  206.4 (8.1)  225.4 (9.2)  210.0 (9.1)
 Female  130.2 (6.2)  147.5 (7.3)  159.2 (9.8)  165.8 (8.0)  174.4 (8.9)  164.0 (9.8)
Interpretation of results:
GHS criteria not met
Conclusions:
The oral LD50 in rats was determined to be > 2000 mg/kg bw.
Executive summary:

The acute oral toxicity of the test item was determined in a 16 -day limit test conducted according to OECD 401. Male and female Fü-albino SPF rats, 6 to 7 weeks old, were dosed with the test item at a nominal concentration 2000 mg/kg bodyweight in Standard Suspending Vehicle by oral gavage. The dose volume was 10 mL/kg. Rats were observed for mortality and clinical signs and body weight. The LD50 was determined to be > 2000 mg/kg bw. There were no effects in body weight development and no clinical signs or autopsy findings were recorded. This study is considered reliable without restriction (Klimisch 1).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
One key study is available (Klimisch 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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
not applicable
Principles of method if other than guideline:
- Principle of test: Male and female rats were exposed to the test item in peanut oil DAB 7 (1:1). The treatment was applied to shaved skin and kept under occlusion for 24 hours. The treated area was then washed with water and rats were observed for 14 days.
- Short description of test conditions: Experimental conditions were maintained at 23 to 33 °C with 45 to 75 % relative humidity. Five male and five females rats were used per treatment and control. Animals were individually caged and provided with food and water ad libitum.
- Parameters analysed / observed: Mortality, intoxication symptoms, local changes, body weight
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Wistar-AF/HAN-EMD-SPF
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 125 to 143 g (mean 137 g)
- Housing: Individually caged in wire cages Type III.
- Diet (e.g. ad libitum): Altromin R, ad libitum.
- Water (e.g. ad libitum): ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 to 33 °C
- Humidity (%): 45 to 75 %
Type of coverage:
occlusive
Vehicle:
peanut oil
Remarks:
DAB 7
Details on dermal exposure:
TEST SITE
- Area of exposure: 6 x 6 cm
- Type of wrap if used: The treated skin area was covered with tin foil, which was fixed and sealed with the aid of a rubber sleeve.

REMOVAL OF TEST SUBSTANCE
- Washing: Yes, substance residues were washed off with water.
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied: 10 mL/kg body weight
- Concentration: 50%
- Constant volume or concentration used: Constant concentration used.

VEHICLE
- Amount(s) applied: 10 mL/kg bodyweight
- Concentration: 50%
Duration of exposure:
24 hours
Doses:
10 g/kg body weight
No. of animals per sex per dose:
5
Control animals:
yes, concurrent vehicle
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: All rats were observed and weighed daily, Monday through Friday.
- Other examinations performed: Evaluation of the changes occurring in the application area was made according to Draize.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 10 000 mg/kg bw
Based on:
test mat.
Remarks on result:
not determinable due to absence of adverse toxic effects
Mortality:
No mortalities were recorded.
Clinical signs:
There were no signs of absorptive intoxication and no symptoms of irritation were observed.
Body weight:
All rats lost weight in the first two days after application. Animals gained weight continuously thereafter.
Gross pathology:
No pathoanatomical abnormalities were observed.

Table 1. Body weights

 Dose (mg/kg)  Sex  Mean body weight (g)                 Difference of final weight from starting weight (g)
     0 days  1 day  3 days  7 days  10 days  14 days  
Vehicle  Male  139  123  132  154  168  187  +48
 Vehicle  Female  142  126  139  148  157  166  +24
 10000  Male  133  117  129  152  165  186  +53
 10000  Female  141  126  136  145  153  161  +20
Interpretation of results:
study cannot be used for classification
Conclusions:
The dermal LD50 in rats was determined to be > 10000 mg/kg bodyweight.
Executive summary:

The acute dermal toxicity of the test item was determined in a 14 -day limit test. A nominal concentration of 10 g/kg bodyweight test item in peanut oil DAB 7 (1:1) was applied to a 6 x 6 cm area of shaved skin of male and female Wistar-AF/HAN-EMD-SPF rats. A vehicle control was included in the study. The treated area was occluded for 24 hours, after which substance residues were washed off with water. Rats were observed for mortality, intoxication, local changes and body weight. The LD50 was determined to be > 10 g/kg bw. There were no signs of absorptive intoxication, symptoms of irritation or pathoanatomical abnormalities. All rats lost weight in the first two days after application, however weight gain was continuous thereafter. This study is considered reliable with restriction (Klimisch 2) as the test was conducted similar to OECD Guideline 402, with minor limitations in reporting.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
10 000 mg/kg bw
Quality of whole database:
One study is available (Klimisch 2) for weight of evidence.

Additional information

The acute oral toxicity of the test item was determined in a limit test conducted according to OECD 401 (1989). Male and female Fü-albino SPF rats, 6 to 7 weeks old, were dosed with the test item at a nominal concentration 2000 mg/kg bodyweight in Standard Suspending Vehicle by oral gavage. The dose volume was 10 mL/kg. Rats were observed for mortality and clinical signs and body weight. The LD50 was determined to be > 2000 mg/kg bw. There were no effects in body weight development and no clinical signs or autopsy findings were recorded. This study is considered reliable without restriction (Klimisch 1).

The acute dermal toxicity of the test item was determined in a 14 -day limit test. A nominal concentration of 10 g/kg bodyweight test item in peanut oil DAB 7 (1:1) was applied to a 6 x 6 cm area of shaved skin of male and female Wistar-AF/HAN-EMD-SPF rats. A vehicle control was included in the study. The treated area was occluded for 24 hours, after which substance residues were washed off with water. Rats were observed for mortality, intoxication, local changes and body weight. The LD50 was determined to be > 10 g/kg bw. There were no signs of absorptive intoxication, symptoms of irritation or pathoanatomical abnormalities. All rats lost weight in the first two days after application, however weight gain was continuous thereafter. This study is considered reliable with restriction (Klimisch 2) as the test was conducted similar to OECD Guideline 402, with minor limitations in reporting.

Justification for classification or non-classification

One key study is available for the acute oral toxicity endpoint and one key studies is available for acute dermal toxicity. All studies were considered to be of robust design and well reported and assigned a Klimisch score of 1 or 2. As the acute oral and dermal studies resulted in predicted LD50 levels in excess of the 2000 mg/kg limit dose, it was concluded that the test item is not classified for acute toxicity according to the CLP Regulation (EC) No 1272/2008.