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Administrative data

Description of key information

Acute oral toxicity: Key study: The acute oral LD50 value of the test substance was >2000 mg/kg bw in female rats.
Acute dermal toxicity: The acute dermal LD50 value of the test substance was >2000 mg/kg bw in male and female rats.

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:
September 11, 2012 - December 12, 2012
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)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS- Source: Charles River Laboratories, Research Models and Services, Germany GmbH, Sandhofer Weg 7, D-97633 Sulzfeld.- Age at study initiation: Young healthy adult rats, approximately 8-9 weeks old.- Weight at study initiation: 171 - 190 g.- Fasting period before study: The night before treatment the animals will be fasted. - Housing: 3 animals/cage.- Diet (e.g. ad libitum): Ad libitum.- Water (e.g. ad libitum): Ad libitum.- Acclimation period: 5-6 daysENVIRONMENTAL CONDITIONS- Temperature (°C): 19.9 – 24.1°C- Humidity (%): 30 - 52 %.- Air changes (per hr): 15-20 air exchanges/hour .- Photoperiod (hrs dark / hrs light): 12 hrs dark / 12 hrs light
Route of administration:
oral: gavage
Vehicle:
water
Remarks:
(distilled)
Details on oral exposure:
VEHICLE:- Amount of vehicle (if gavage): 200 mg/mL- Lot/batch no. (if required): 3450611MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bwDOSAGE PREPARATION (if unusual): The test item was freshly formulated at a concentration of 200 mg/mL in the vehicle. The formulation container was stirred continuously up to finishing the treatment. The purity factor was 2.18, therefore the dose to be adjusted was 2000 x 2.18 mg/kg bw prepared in distilled water at a dose volume of 10 ml/kg bw. With this the dose level was 2000 mg/kg bw referring to the dry component (46%) of the test item.CLASS METHOD (if applicable)- Rationale for the selection of the starting dose: In the lack of any preliminary toxicological information, 2000 mg/kg bw was selected to be the starting dose.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
3 females rats per group (group 1 and confirmatory group 2).
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days.- Frequency of observations and weighing: Clinical observations were performed on all animals at 30 minutes, 1, 2, 3, 4 and 6 hours after dosing and daily for 14 days thereafter. Body weight was measured on Days -1, 0 and 7 and Day 14 before necropsy.- Necropsy of survivors performed: Yes, all animals were subjected to a necropsy and a macroscopic examination.
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
Treatment did not cause mortality.
Clinical signs:
Treatment caused decreased activity, hunched back and piloerection.
Body weight:
Body weight gains did not show any test item related effect during the study.
Gross pathology:
Treatment was not associated with any test item related gross findings.
Table 1. Clinical observations.

 

Dose level: 2000 mg/kg bw, Treatment on day 0.                                     Sex: Female.

Cage No.

Animal number

Observations

Observation days

Frecuency

0

1

2

3

4

5

6-14

30’

1h

2h

3h

4h

6h

1

8156

Symptom Free

-

-

-

-

-

-

-

+

+

+

+

+

13/20

Activity decreased

-

-

-

1

1

-

-

-

-

-

-

-

2/20

Hunched back

+

+

+

+

+

+

-

-

-

-

-

-

6/20

Piloerection

-

-

+

+

+

+

+

-

-

-

-

-

5/20

8157

Symptom Free

-

-

-

-

-

-

+

+

+

+

+

+

14/20

Activity decreased

-

-

-

1

1

-

-

-

-

-

-

-

2/20

Hunched back

+

+

+

+

+

+

-

-

-

-

-

-

6/20

Piloerection

-

-

+

+

+

-

-

-

-

-

-

-

3/20

8158

Symptom Free

-

-

-

-

-

-

+

+

+

+

+

+

14/20

Activity decreased

-

-

-

1

-

-

-

-

-

-

-

-

1/20

Hunched back

+

+

+

+

+

+

-

-

-

-

-

-

6/20

Piloerection

-

-

+

+

+

-

-

-

-

-

-

-

3/20

2

8159

Symptom Free

-

-

-

-

-

-

+

+

+

+

+

+

14/20

Hunched back

+

+

+

+

+

+

-

-

-

-

-

-

6/20

Piloerection

-

-

-

+

+

-

-

-

-

-

-

-

2/20

8160

Symptom Free

-

-

-

-

-

-

+

+

+

+

+

+

14/20

Hunched back

+

+

+

+

+

+

-

-

-

-

-

-

6/20

Piloerection

-

-

-

+

+

-

-

-

-

-

-

-

2/20

8161

Symptom Free

-

-

-

-

-

-

+

+

+

+

+

+

14/20

Hunched back

+

+

+

+

+

+

-

-

-

-

-

-

6/20

Piloerection

-

-

-

+

+

-

-

-

-

-

-

-

2/20

Remarks:

+ = present                          - = absent

h = hour (s)                          ‘ = minute

Frequency of observation = number of occurrence of observation / total number of observations

Severities: 1 = Slight/Small/Few; 2 = Moderate/Medium; 3 = Marked/Large/Many

 

  

Table 2. Body weight data.

 

Dose level: 2000 mg/kg bw, Treatment on day 0.                                     Sex: Female.

Cage No.

Animal number

Body weight (g)

Days

Body Weight Gain (g)

-1

0

7

14

-1 - 0

0 - 7

7 - 14

-1 - 14

1

8156

191

181

203

224

-10

22

21

33

8157

200

184

224

252

-16

40

28

52

8158

198

187

217

229

-11

30

12

31

2

8159

185

171

198

205

-14

27

7

20

8160

195

189

218

226

-6

29

8

31

8161

199

190

221

238

-9

31

17

39

Mean:

194.7

183.7

213.5

229.0

-11.0

29.8

15.5

34.3

Standard deviation:

5.8

7.0

10.5

15.6

3.6

5.9

8.1

10.6

 

  

Table 3. Necropsy findings.

 

Dose level: 2000 mg/kg bw, Treatment on day 0.                                     Sex: Female.

Cage No.

Animal number

Necropsy Day

External Observations

Internal Observations

Organ/Tisuue

1

8156

Day 14

No external observations recorded

No internal observations recorded

Not applicable

8157

Day 14

No external observations recorded

No internal observations recorded

Not applicable

8158

Day 14

No external observations recorded

No internal observations recorded

Not applicable

2

8159

Day 14

No external observations recorded

No internal observations recorded

Not applicable

8160

Day 14

No external observations recorded

No internal observations recorded

Not applicable

8161

Day 14

No external observations recorded

No internal observations recorded

Not applicable

 

 

Interpretation of results:
not classified
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
The acute oral LD50 value of the test substance was >2000 mg/kg bw in female rats.
Executive summary:

The single-dose oral toxicity was performed according to OECD 423 Guideline and EU B.1tris Method (acute toxic class method) in female CRL: (WI) rats. Two groups (one confirmatory group) of three rats were exposed by single oral treatment to 2000 mg/kg bw. Mortality, clinical observations and body weight were analyzed for 14 days after exposure. In day 14, necropsy was performed and all animals were subjected to a necropsy and a macroscopic examination. No effects on mortality, body weight and macroscopic findings were observed. Treatment caused decreased activity, hunched back and piloerection. Under the conditions of this study, the acute oral LD50 was determined to be greater than 2000 mg/kg bw in female rats.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 001 mg/kg bw
Quality of whole database:
The study is a GLP compliant and has Klimisch score 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:
September 12, 2012 - December 12, 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS- Source: Charles River Laboratories, Research Models and Services, Germany GmbH, Sandhofer Weg 7, D-97633 Sulzfeld.- Age at study initiation: Young adult rats.- Weight at study initiation: Males: 231-242 g, Females: 213-234 g- Housing: Individual caging.- Diet (e.g. ad libitum): Ad libitum.- Water (e.g. ad libitum): Ad libitum.- Acclimation period: 6 days.ENVIRONMENTAL CONDITIONS- Temperature (°C): 20.6 – 25°C.- Humidity (%): 30 - 54 %.- Air changes (per hr): 15-20 air exchanges/hour .- Photoperiod (hrs dark / hrs light): 12 hrs dark / 12 hrs light
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE- Area of exposure: back of the animals.- % coverage: 10% of the total body.- Type of wrap if used: Sterile gauze pads were placed on the skin to cover the test item. These gauze pads were kept in contact with the skin by a patch with adhesive hypoallergenic plaster. The entire trunk of the animal was then wrapped with semi occlusive plastic wrap for 24 hours.REMOVAL OF TEST SUBSTANCE- Washing (if done): The area of skin treated with the test item was washed with water of body temperature.- Time after start of exposure: 24 hoursTEST MATERIAL- Concentration: Purity factor of 2.18 to the dry content of the test item was used
Duration of exposure:
24 hour
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 animals/sex
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days- Frequency of observations and weighing: Clinical observations were performed on all animals at 1 and 5 hours after dosing and daily for 14 days thereafter. Body weight was measured prior to dosing on Day 0 and on Days 7 and 14. - Necropsy of survivors performed: Yes, gross macroscopic examination was performed on all animals at the end of the 2-week observation period (Day 14).
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
Administration of the test item did not cause mortality.
Clinical signs:
No clinical signs were observed after treatment or during the 14 day observation period.
Body weight:
The body weight and body weight gain of surviving animals did not show any test item-related effect.
Gross pathology:
No macroscopic effects were observed at necropsy.
Other findings:
Local dermal signs: Multifocal erythema in different diameters from 2 – 4 mm was noted in 4/5 males and 3/5 females which was reversible within 72 hours. In case of one male, a wound covered with scab later was observed from Day 2 to Day 9. Yellow discoloration of the fur was observed at the outskirt of the exposed surface in 5/5 males and 5/5 females.

Experimental results are included in the tables which contains the document attached ("Attached background material").

Interpretation of results:
not classified
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
The acute dermal LD50 value of the test substance was >2000 mg/kg bw in male and female rats.
Executive summary:

The acute dermal toxicity of test substance was performed according to OECD 402 Guideline and EU B.3 Method in male and female rats. A limit test was carried out at 2000 mg/kg body weight (bw) in both sexes (5 rats/sex). The test item was applied under semi-occlusive conditions as supplied as a single dermal 24-hour exposure followed by a 14‑day observation period. No treatment related effects were observed on mortality, clinical signs, body weight and necropsy. Multifocal erythema in different diameters were noted which were reversible within 72 hours. In case of one male, a wound covered with scab later was observed from day 2 to 9. Yellow discoloration of the fur was observed at the outskirt of the exposed surface in all animals. The acute dermal median lethal dose (LD50) of the test substance was found to be higher than 2000 mg/kg bw in male and female rats.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 001 mg/kg bw
Quality of whole database:
The study is a GLP compliant and has Klimisch score 1.

Additional information

Acute oral toxicity: Key study: The single-dose oral toxicity was performed according to OECD 423 Guideline and EU B.1tris Method (acute toxic class method) in female CRL: (WI) rats. Under the conditions of this study, the acute oral LD50 was determined to be greater than 2000 mg/kg bw in female rats.

Acute dermal toxicity: Key study: The acute dermal toxicity was performed according to OECD 402 Guideline and EU B.3 Method in male and female rats. A limit test was carried out at 2000 mg/kg body weight (bw) in both sexes (5 rats/sex) under semi-occlusive conditions. The acute dermal median lethal dose (LD50) of the test substance was found to be higher than 2000 mg/kg bw in male and female rats.

Acute toxicity by inhalation: Data waiving (other justification): According to REACH Annex VIII, column 2: In addition to the oral route, for substances other than gases, the information mentioned under 8.5.2 to 8.5.3 shall be provided for at least one other route. The choice for the second route will depend on the nature of the substance and the likely route of human exposure. If there is only one route of exposure, information for only that route need be provided. The information is provided for dermal route.


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

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

Justification for classification or non-classification

Oral acute toxicity LD50> 2000 mg/kg: not classified.

Dermal acute toxicity LD50> 2000 mg/kg: not classified.

Based on the available data, the substance is not classified for acute oral and dermal toxicity (LD50 > 2000 mg/kg bw) according to CLP Regulation no. 1272/2008.