Registration Dossier

Diss Factsheets

Toxicological information

Acute Toxicity: dermal

Currently viewing:

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 7 April 2017 to 2 June 2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2017
Report date:
2017

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
Relative humidity value (28%) outside the expected range of 30-70% was recorded at one time. This deviation was considered to have no impact on the outcome of the study.
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Reference substance name:
Sulfates of potassium, sodium and calcium, byproduct from fermentation
Molecular formula:
SO42-, K+, Na+, Ca2+
IUPAC Name:
Sulfates of potassium, sodium and calcium, byproduct from fermentation
Test material form:
solid
Remarks:
light to beige solid
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: EXP LIberica Lote Al16503047
- Expiration date of the lot/batch: 30 November 2019
- Purity test date: 1 February 2017

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Controlled room temperature (15-25 deg Celsius, below 70% relative humidity) protected from light and humidity
- Stability under test conditions: not applicable
- Solubility and stability of the test substance in the solvent/vehicle: not applicable

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
The test item was ground to a fine powder before the application. Sufficient water was used to dampen the test material to ensure good contact with the skin.

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services, Germany
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: Young adult rats
- Weight at study initiation: Between 219 g and 266 g
- Fasting period before study: No
- Housing: Type II. polypropylene/polycarbonate
- Diet (e.g. ad libitum): ssniff® SM R/M "Autoclavable complete diet for rats and mice breeding and maintenance", ad libitum
- Water (e.g. ad libitum): tap water from the municipal supply, as for human consumption from a 500 mL bottle, ad libitum
- Acclimation period: 5 Days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.4–24.7°C
- Humidity (%): 28–61%
- Air changes (per hr): 15-20 air exchanges/hour
- Photoperiod (hrs dark / hrs light): 12 hours daily, from 6.00 a.m. to 6.00 p.m.

IN-LIFE DATES: From: 6 April 2017 To: 25 April 2017

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
water
Details on dermal exposure:
TEST SITE
- Area of exposure: back of the animals
- % coverage: approximately 10% area of the total body surface
- Type of wrap if used: Sterile gauze pads maintened with adhesive hypoallergenic plaster.The entire trunk was wrapped with semi occlusive plastic wrap for 24 hours

REMOVAL OF TEST SUBSTANCE
- Washing (if done): washing with water at body temperature
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- Concentration (if solution): not applicable
- Constant volume or concentration used: adjusted to animal bodyweight
- For solids, paste formed: yes
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 animals per sex per dose were used
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 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. The body weights were recorded on Day 0 (before the test item administration) and on Days 7 and 14 (before necropsy). Adverse skin reactions at the site of application were recorded daily following the removal of the dressing.
- Necropsy of survivors performed: yes

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
The test item did not cause mortality at the dose level of 2000 mg/kg bw.
Clinical signs:
There were no systemic clinical signs noted in any animal throughout the study
Body weight:
There were no treatment related effects on body weight or body weight gain during the observation period.
Gross pathology:
There was no evidence of any gross macroscopic changes at a dose level of 2000 mg/kg bw.
Other findings:
No adverse local dermal signs were observed after treatment with the test item or during the 14 days observation period.

Any other information on results incl. tables

TABLE 1:            Clinical Observations

 

DOSE LEVEL: 2000mg/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

7970

Symptom Free

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

16/16

2

7971

Symptom Free

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

16/16

3

7972

Symptom Free

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

16/16

4

7973

Symptom Free

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

16/16

5

7974

Symptom Free

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

16/16

 

DOSE LEVEL: 2000mg/kg bw                                                                                      SEX:FEMALE

 

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

6

7985

Symptom Free

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

16/16

7

7986

Symptom Free

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

16/16

8

7987

Symptom Free

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

16/16

9

7988

Symptom Free

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

16/16

10

7989

Symptom Free

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

16/16

 

Remarks:         += present

h =hour(s)               Treatment day = Day0

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


 

TABLE 2:            Body Weight Data

 

DOSE LEVEL: 2000mg/kgbw                                                                              SEX:MALE

 

Cage No.

 

Animal No.

Body weight (g) Days

 

Body Weight Gain (g)

0

7

14

0-7

7-14

0-14

1

7970

253

310

369

57

59

116

2

7971

238

272

307

34

35

69

3

7972

242

305

361

63

56

119

4

7973

241

285

339

44

54

98

5

7974

234

273

313

39

40

79

Mean:

241.6

289.0

337.8

47.4

48.8

96.2

Standard deviation:

7.1

17.7

27.7

12.2

10.6

22.1

 

DOSE LEVEL: 2000mg/kgbw                                                                         SEX:FEMALE

 

Cage No.

 

Animal No.

Body weight (g) Days

 

Body Weight Gain (g)

0

7

14

0-7

7-14

0-14

6

7985

264

276

298

12

22

34

7

7986

266

272

277

6

5

11

8

7987

256

270

279

14

9

23

9

7988

234

238

246

4

8

12

10

7989

219

257

260

38

3

41

Mean:

247.8

262.6

272.0

14.8

9.4

24.2

Standard deviation:

20.5

15.5

19.8

13.6

7.4

13.3


 

TABLE 3:            Macroscopic Findings

 

DOSE LEVEL: 2000mg/kgbw                                                                                      SEX:MALE

Cage No.

Animal No.

Necropsy Date/ Necropsy Day

External Observations

Internal Observations

Organ/ Tissue

1

7970

25 April 2017

Day 14

No external observations

No internal observations

Not applicable

2

7971

25 April 2017

Day 14

No external observations

No internal observations

Not applicable

3

7972

25 April 2017

Day 14

No external observations

No internal observations

Not applicable

4

7973

25 April 2017

Day 14

No external observations

No internal observations

Not applicable

5

7974

25 April 2017

Day 14

No external observations

No internal observations

Not applicable

 

DOSE LEVEL: 2000mg/kgbw                                                                                  SEX:FEMALE

 

Cage No.

Animal No.

Necropsy Date/ Necropsy Day

External Observations

Internal Observations

Organ/ Tissue

6

7985

25 April 2017

Day 14

No external observations

No internal observations

Not applicable

7

7986

25 April 2017

Day 14

No external observations

No internal observations

Not applicable

8

7987

25 April 2017

Day 14

No external observations

No internal observations

Not applicable

9

7988

25 April 2017

Day 14

No external observations

No internal observations

Not applicable

10

7989

25 April 2017

Day 14

No external observations

No internal observations

Not applicable


 

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The acute dermal median lethal dose (LD50) of the test item Sulfates of potassium, sodium and calcium, by-product from fermentation was found to be greater than 2000 mg/kg body weight in male and female Crl:WI rats. According to the CLP criteria, the test item was not classified for Acute Dermal Hazard.
Executive summary:

The purpose of this GLP compliant study was to assess the potential Acute Toxicity of the test substance Sulfates of potassium, sodium and calcium, by-product from fermentation, when applied dermally on Wistar rats, perfomed according to OECD 402 method.

A limit test  was  carried  out  at  2000 mg/kg  body  weight  (bw)  in  both sexes (5 rats/sex). The test item was powdered and was applied 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 (before necropsy). Gross macroscopic examination was performed on all animals at the end of the 2-week observation period (Day 14).

Test item did not cause mortality at the dose level of 2000 mg/kg bw.

There were no systemic clinical signs noted in any animal throughout the study.

No adverse local dermal signs were observed after treatment with the test item or during the 14 days observation period.

There were no treatment related effects on body weight or body weight gain during the observation period.

There was no  evidence  of  any  macroscopic  changes  at  a  dose  level  of  2000 mg/kg bw.

The  acute  dermal  median  lethal  dose  (LD50)   of   the   test   item   Sulfates of potassium, sodium and calcium, by-product from fermentation was found to be greater than 2000 mg/kg body weight in male and female Crl:WI rats. According to the CLP criteria, the test item was not classified for Acute Dermal Hazard.

Categories Display