Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
4.4.-20.4.2006
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This study was carried out in accordance with internationally valid GLP principles.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2006
Report Date:
2006

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Potassium permanganate
- Molecular formula (if other than submission substance): KMnO4
- Molecular weight (if other than submission substance): 158.03
- Batch No.: 69
- Substance type: technical product
- Physical state: solid crystals
- Analytical purity: 99.42 % wt.
- Impurities (identity and concentrations): Manganese dioxide ca 0.1 % wt.
- Appearance: dark violet-purple crystalline powder with bronze lustre
- pH: 1% solution-6.1

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: breeding farm BioTest s. r. o., Konárovice, 281 25 CZ, Czech Republic
- Weight at study initiation: 199.14 - 318.21 g
- Housing: animal room with monitoring conditions - one animal in one plastic cage
- Bedding: sterilized shavings of soft wood
- Diet: ad libitum; ST 1 BERGMAN - standard pelleted diet ad libitum (producer: Mill Kocannda, Jesenice u Prahy, Czech Republic)
- Water: ad libitum; drinking tap water quality corresponding to Regulation No. 252/2004 Czech. Coll. of Law
- Acclimation period: 15 days
- Randomisation: according to the internal rule, at the start of the study the weight variation of animals was minimal and did not exceed (+/-)
20% of the mean weight for each sex
- Identification of animals: colour marks on tail of animals, each cage was marked with the number of study, number of animals, sex, name and dose of the test substance
- Health condition: certificate of goodhealth condition, no signs of diseases were observed at clinical check-in during the acclimatisation period
and before the start of study



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


Study time schedule
Animal supply: 20. 3. 2006
Experimental part of study: 4. 4. – 20. 4. 2006
Evaluation of results and final report elaboration: 21. 4. – 15. 5. 2006

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: 6 cm x 6 cm
- % coverage: 10 % of the body surface
- Type of wrap if used: the application site was covered by mull, plastic foil and held in contact by plaster (strapping)

REMOVAL OF TEST SUBSTANCE
- Washing: with water
- Time after start of exposure: 24 hours

TEST MATERIAL
The test substance in delivered form (moistened with the smallest amount of water) was applied on the depilated area of skin.
- Amount(s) applied (volume or weight with unit): 2000 mg/kg

VEHICLE
- Amount(s) applied (volume or weight with unit): no vehicle was used
Duration of exposure:
24 hours
Doses:
2000 mg/kg of body weight
No. of animals per sex per dose:
5 female/5 male
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
Body weight recording:
The animals were weighed at the start of the study (before application), at 8th day and in the end of experiment (15th day).
Average body weight in-group was counted from individual body weights. Body weight increments were calculated from body weight at the start of
the study and in the end of the study.

Clinical observation:
After application the animals were observed individually – the first day: twice (30 minutes and 3 hours after application), the second day: twice (in the morning and in the afternoon) and daily thereafter for 14 days.
Observations included changes in skin and fur, eyes, visible mucous membranes, nutritive condition, autonomic and central nervous systems, psychic activity, somatomotor activity, reactions to stimuli, function of respiratory, circulatory, digestive and urogenital system. Also presence of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma was carefully observed.

Pathological examination:
On the 15th day of study all test animals were sacrificed (by injection of veterinary formulation T 61, 1ml/animal) and gross necropsy was carried out.Size, colour, shape, structure and consistency of organs were evaluated. All gross macroscopic changes of organs and tissues were recorded in protocols.


Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No death of animals was observed during 14 days observation period.
Clinical signs:
No clinical signs of intoxication of animals were observed.
See tables No. 3 and No. 4
Body weight:
Weight increments in males were in physiological range, only body weight gains of females were markedly lower.
See tables No. 1 and No. 2
Gross pathology:
No death of animals was observed during 14 days observation period.
Macroscopic changes were diagnosed during pathological examination in all animals.
See tables No. 5 and No. 6
Other findings:
- Organ weights: none
- Histopathology: none
- Potential target organs: none
- Other observations: none

Any other information on results incl. tables

Table No.1: Individual body weight of animals - 2000 mg/kg - males

Animal No.

Before application

8th day

15th day

Increment

1

294.39

321.26

376.37

81.98

2

318.21

339.30

387.66

69.45

3

277.53

296.43

323.55

46.02

4

269.14

291.20

339.70

70.56

5

263.13

283.25

313.62

50.49

Average

284.48

306.29

348.18

63.70

Table No. 2: Individual body weight of animals - 2000 mg/kg - females

Animal No.

Before application

8th day

15th day

Increment

1

223.99

232.82

240.12

16.13

2

199.14

204.77

221.72

22.58

3

213.85

216.47

231.97

18.12

4

224.95

248.62

261.44

36.49

5

208.20

224.67

237.01

28.81

Average

214.03

225.47

238.45

24.42

Table No.3: Clinical observations - 2000 mg/kg - males

Animal No.

Death after application

Changes

1

no

No clinical changes

2

no

No clinical changes

3

no

No clinical changes

4

no

No clinical changes

5

no

No clinical changes

Table No. 4: Clinical observations - 2000 mg/kg - females

Animal No.

Death after application

Changes

1

no

No clinical changes

2

no

No clinical changes

3

no

No clinical changes

4

no

No clinical changes

5

no

No clinical changes

Table No.5: Pathological examination - 2000 mg/kg – males 

Animal No.

         

Findings

1

Kidney - marked structure

2

Kidney - marked structure

3

Liver – marked structure

Kidney - marked structure

4

Kidney - marked structure

5

Kidney - marked structure

Table No. 6: Pathological examination - 2000 mg/kg – females 

Animal No.

         

Findings

1

Kidney - marked structure

2

Kidney - marked structure

3

Liver – marked structure

Kidney - marked structure

4

Kidney - marked structure

5

Kidney - marked structure

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
The test substance toxicity was evaluated on the basis of mortality, body weight changes, clinical signs of toxicity during the observation period
and necropsy findings in the end of study.
The test substance applied on skin in dose 2000 mg/kg did not cause death of animals. Macroscopic changes were diagnosed during pathological examination in all animals.
No clinical signs of intoxication of animals were observed, but markedly lower body weight gains of females were recorded.
Executive summary:

The test substance Potassium permanganate was tested for the assessment of acute dermal toxicity using Wistar rats.

    Testing was performed according to the Method B.3 Acute Toxicity (Dermal), Directive 92/69/EEC. Published in OJ L 383A, 1992.

    The study was performed as limit test: two groups of animals – 5 males and 5 females and the dose of 2000 mg/kg. The test substance was applied on the shaved skin of the test animals in delivered form for 24 hours.

    The test animals were observed 14 days after application, afterwards were sacrificed and the necropsy for macroscopic examination of the organs was performed.

   The test substance applied in dose 2000 mg/kg did not caused death of animals. Macroscopic changes were diagnosed during pathological examination in all animals.

   No clinical signs of toxicity were observed during the study in all animals, but markedly lower body weight gains of females were recorded.

    According to the results of study the value of LD50 dermal of the test substance Potassium permanganate for rats of both sexes is higher than 2000 mg/kg.