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Toxicological information

Acute Toxicity: dermal

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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 27 APR 2011 to 11 MAY 2011
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2011
Report Date:
2011

Materials and methods

Test guidelineopen allclose all
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)
Remarks:
according to Hungarian GLP Regulations: 9/2001 (III.30.) which comply with OECD/European community requirements
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Janvier S.A.S.
- Age at study initiation:young adult rats
- Weight at study initiation: between 211 and 245 g
- Housing: individual caging in type II cages (polypropylene/polycarbonate) with Lignocel Hygienic Animal Bedding produced by J. Rettenmaier & Söhne GmbH+Co.KG (Holzmühle 1, 73494 Rosenberger, Germany);
- Diet: ssniff® SM R/M-Z+H "Autoclavable complete feed for rats and mice – breeding and maintenance" produced by ssniff Spezialdiäten GmbH, D-59494
Soest Germany; ad libitum
- Water: tap water from municipal supply; ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.4 to 24.8
- Humidity (%): 31 to 68
- Air changes (per hr): 15 to 20
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: back
- % coverage: 10% of total body surface
- Type of wrap if used: Sterile gauze pads were placed on the skin of rats 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): with water of body temperature
- Time after start of exposure: 24 hours
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:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: once weekly (recorded on Day 0 (before test item administration) and on Days 7 and 14)
- Necropsy of survivors performed: yes (All animals were anaesthetised with Euthasol® 40% and exsanguinated. After examination of the external appearance, the cranial, thoracic and abdominal cavities were opened and the appearance of the tissues and organs was observed. All macroscopic changes were recorded.)
- Other examinations performed: clinical signs (Clinical observations were performed on the day of treatment at 1 and 5 hours after application of the test item and once each day for 14 days thereafter. Observations included the skin and fur, eyes and mucous membranes, the respiratory, circulatory, autonomic and central nervous system, somatomotor activity and behaviour pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.)

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: no animal died during the 14-day observation period
Mortality:
No mortality occurred after a 24-hour dermal exposure of test material administered at 2000 mg/kg bw to RjHan:(WI) Wistar rats followed by a 14-day observation period.
Clinical signs:
No clinical signs were observed after the treatment with the test item or during the 14-day observation period.
Body weight:
Body weight development was not impaired.
Gross pathology:
There was no evidence of the test item-related observations at a dose level of 2000 mg/kg bw at necropsy.
Other findings:
After treatment with the test material no local signs were observed after the treatment with the test item or during the 14-day observation period.

Any other information on results incl. tables

INDIVIDUAL CLINICAL OBSERVATIONS

DOSE LEVEL: 200 mg/kg bw                                                                                               SEX: MALE

Cage No.

Animal No.

Observations

Observation days

Frequency

0

1

2

3

4

5

6

7

8

9

10

11

12

13

14

1h

5h

1

6235

Symptom Free

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

16/16

2

6236

Symptom Free

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

16/16

3

6237

Symptom Free

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

16/16

4

6238

Symptom Free

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

16/16

5

6239

Symptom Free

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

16/16

DOSE LEVEL: 2000 mg/kg bw                                                                                                                         SEX: FEMALE

6

6240

Symptom Free

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

16/16

7

6241

Symptom Free

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

16/16

8

6242

Symptom Free

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

16/16

9

6243

Symptom Free

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

16/16

10

6244

Symptom Free

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

16/16

Remarks:            +: present

                               h=hour (s)                          Treatment day=Day 0

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

INDIVIDUAL BODY WEIGHT AND BODY WEIGHT GAIN

DOSE LEVEL: 2000 mg/kg bw                                                 SEX: MALE

Cage No.

Animal No.

Body Weight (g) Days

Body Weight Gain (g)

0

7

14

0-7

7-14

0-14

1

6235

234

275

336

41

61

102

2

6236

242

294

357

52

63

115

3

6237

236

290

352

54

62

116

4

6238

245

292

351

47

59

106

5

6239

230

284

341

54

57

111

Mean:

237.4

287.0

347.4

49.6

60.4

110.0

Standard deviation:

6.1

7.7

8.6

5.6

2.4

6.0

DOSE LEVEL: 2000 mg/kg bw                                             SEX: FEMALE

6

6240

224

227

253

3

26

29

7

6241

211

231

243

20

12

32

8

6242

217

220

237

3

17

20

9

6243

218

226

244

8

18

26

10

6244

221

231

245

10

14

24

Mean:

218.2

227.0

244.4

8.8

17.4

26.2

Standard deviation:

4.9

4.5

5.7

7.0

5.4

4.6

Remark:              Treatment day = Day 0

 

INDIVIDUAL INTERNAL AND EXTERNAL MACROSCOPIC OBSERVATIONS

DOSE LEVEL: 2000 mg/kg bw                                                                                                                         SEX: MALE

Cage No.

Animal No.

External Observations

Internal Observations

Organ/Tissue

1

6235

No external observations

No internal observations

Not applicable

2

6236

No external observations

No internal observations

Not applicable

3

6237

No external observations

No internal observations

Not applicable

4

6238

No external observations

No internal observations

Not applicable

5

6239

No external observations

No internal observations

Not applicable

DOSE LEVEL: 2000 mg/kg bw                                                                                                                      SEX: FEMALE

6

6240

No external observations

No internal observations

Not applicable

7

6241

No external observations

No internal observations

Not applicable

8

6242

No external observations

In estrus

Uterus

9

6243

No external observations

No internal observations

Not applicable

10

6244

No external observations

No internal observations

Not applicable

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this limit test the acute dermal median lethal dose (LD50) of the test item was found to be higher than 2000 mg/kg body weight in male and female RjHan:(WI) Wistar rats.
Executive summary:

An acute dermal toxicity study was performed with the test material in RjHan:(WI) Wistar rats, in compliance with OECD Guideline No.: 402. A limit test was carried out at 2000 mg/kg body weight (bw) in both sexes (5 rats/sex). The test item was applied as supplied as a single dermal 24-hour exposure followed by a 14-day observation period. 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. Rats were euthanized and a gross macroscopic examination performed at the end of the 2-week observation period (Day 14). The results of the study were summarized as follows: No mortality occurred. No clinical signs were observed after the treatment with the test item or during the 14-day observation period and no local dermal signs were existing. The body weight and body weight gain of treated animals did not show any adverse effects. There was no evidence of the test item-related observations at a dose level of 2000 mg/kg bw at necropsy. Taken from this observations a LD50 is > 2000 mg/kg body weight.