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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:
14 November 2018 - 13 December 2018
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2018
Report date:
2018

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
fixed dose procedure
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: In-house bred animals
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 9 to 10 weeks
- Weight at study initiation: 256.78 (mean weight of the 5 animals tested)
- Fasting period before study: Animals were fasted overnight (16 to 18 hours) prior to dosing. Water was provided ad libitum during fasting period. Feed was offered 3 to 4 hours after dosing.
- Housing: Maximum of three animals were housed in a standard polypropylene cage (size: L 430 x B 285 x H 150 mm) with stainless steel mesh top grill having facilities for holding pelleted feed and drinking water in water bottle fitted with stainless steel sipper tube. For range finding study, animals were housed individually after treatment throughout the observation. For main study, during treatment, the animals were housed individually and after patch removal they were housed together. Clean sterilized paddy husk was provided as bedding material. Paper shredding was provided as enrichment.
- Diet (e.g. ad libitum): Ad libitum. Altromin Maintenance Diet for rats and mice (manufactured by Altromin Spezialfutter GmbH & Co. KG).
- Water (e.g. ad libitum): Ad libitum. Deep bore-well water passed through Reverse osmosis unit was provided in plastic water bottles with stainless steel sipper tubes.
- Acclimation period: the animals were acclimatized for at least 5 days before treatment.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.3ºC to 22.8ºC
- Humidity (%): 46 to 66%
- Air changes (per hr): 12-15 air changes/hour
- Photoperiod (hrs dark / hrs light): 12 hours light and 12 hours dark cycle.

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: dorso-lateral area of the trunk.
- % coverage: at least 10% of the body surface area.
- Type of wrap if used: semi-occlusive dressing (crepe bandage).

REMOVAL OF TEST SUBSTANCE
- Washing (if done): residual test item was washed using distilled water and dried with absorbent cotton.
- Time after start of exposure: 24h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 200, 1000 and 2000 mg/kg body weight
- Concentration (if solution): N/A
- Constant volume or concentration used: No; Volume applied (mL) = [Dose (mg/kg)/1000 x Body weight (g)/Density (mg/mL)]
- For solids, paste formed: N/A
Duration of exposure:
24 h
Doses:
Range finding study: 200, 1000 and 2000 mg/kg body weight
Main study: 2000 mg/kg body weight
No. of animals per sex per dose:
Range finding study: 1 female per dose
Main study: 2 females per dose
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: At each step, the animals were observed for clinical signs of toxicity and mortality at 20 to 30 min, 1 hr (±10 mins), 2 hrs (±10 mins), 4 hrs (±10 mins) and 6 hrs (±10 mins) post dosing on Day 1 and thereafter once daily for clinical signs of toxicity and twice daily for mortality. Individual animal body weight was recorded at receipt, on day 1 before test item application and on day 8 and day 15 during the experimental period.
- Necropsy of survivors performed: yes. At termination, gross pathological findings were recorded and reported.
- Other examinations performed:
Clinical observations: changes in skin, fur, eyes and mucous membranes along with changes in respiratory, circulatory, autonomic and central nervous system, somatomotor activity and behaviour pattern.

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred during both range finding study and main study.
Clinical signs:
No treatment related clinical signs of toxicity were observed in both range finding study and main study animals.
Body weight:
All animals revealed physiologically normal increase in the body weight in both range finding study and main study.
Gross pathology:
No treatment related gross pathological changes were observed in any of the animals in both range finding study and main study animals.

Any other information on results incl. tables

Table 1:Individual animal clinical signs of toxicity and mortality record

Phase of the Experiment

 

Dose (mg/kg body weight)

Animal No.

Sex

Time of Dosing

(AM)

Clinical Signs of Toxicity and Mortality on Day 1

Clinical Signs of Toxicity and Mortality on days

20-30

mins

1 hr

(±10 mins)

2 hrs

(±10 mins)

4 hrs

(±10 mins)

6 hrs

(±10 mins)

2

3

4

5

6

7

8

9

10

11

12

13

14

15

Range Finding Study

200

Rd2498

F

10:58

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

1000

Rd2499

F

10:56

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

2000

Rd2500

F

10:54

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Main Study

2000

Rd2501

F

11:18

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rd2502

F

11:20

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N: Normal; F: Female; min: minutes; hr/hrs: hour/hours

Table 2: Individual animal body weight (g) and percent change in body weight with respect to day 1

Phase of the Experiment

Dose (mg/kg)

Animal No.

Sex

Body Weight (g) on Days

Percent Change in Body Weight with Respect to Day

1

8

15

1 to 8

1 to 15

Range Finding Study

200

Rd2498

F

250.15

268.38

285.71

7.29

14.22

1000

Rd2499

F

245.11

263.27

284.52

7.41

16.08

2000

Rd2500

F

265.53

283.47

301.23

6.76

13.44

Main Study

2000

Rd2501

F

262.04

281.40

297.94

7.39

13.70

Rd2502

F

251.51

272.18

287.07

8.22

14.14

Mean

 

256.78

276.79

292.51

7.80

13.92

±SD

 

7.45

6.52

7.69

0.59

0.31

Applicant's summary and conclusion

Interpretation of results:
other: No category (CLP Regulation EC no. 1272/2008)
Conclusions:
The LD50 of the test item is higher than 2000 mg/kg body weight by dermal route in rats.

Executive summary:

The acute dermal toxicity of the test item was studied according to OECD Guideline 402 (GLP study). 5 female Sprague-Dawley rats were tested for a exposure period of 24 h. Initially, a range finding study was conducted at doses of 200, 1000 and 2000 mg/kg bw in one animal per dose. Based on the results of this preliminary study two additional rats were tested at a dose of 2000 mg/kg bw. No treatment related clinical signs of toxicity and mortality were observed. The body weight evolution of the animals remained normal during the study. The macroscopic examination of the animals at the end of the study did not reveal treatment related effects. Based on these results, the test item was found to be non toxic, with an LD50 > 2000 mg/kg bw.