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Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Justification for type of information:
Data is from experimental reports

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013
Report date:
2013

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Principles of method if other than guideline:
The test compound was tested for its dermal irritation potential in New Zealand White Rabbits according to guideline OECD-404.
GLP compliance:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Benzimidazole-2-thiol
EC Number:
209-502-6
EC Name:
Benzimidazole-2-thiol
Cas Number:
583-39-1
Molecular formula:
C7H6N2S
IUPAC Name:
1H-benzimidazole-2-thiol
Details on test material:
SOURCE OF TEST MATERIAL
- Test substance: 2-mercaptobenzimidazole (benzimidazole-2-thiol) (CAS No. 583-39-1) is a pale yellow white powder with a molecular weight of 150.21.
- Source of test material: Sumitomo Chemical Co., Ltd.
- Lot number: 30807
- Purity: 98.5%
- Substance type: Organic
- Physical state: Solid
- Molecular formula: C7H6N2S
- Molecular weight: 150.204 g/mol

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: The test substance was kept at room temperature with light shielding until use.
- Stability under test conditions: No data
- Solubility and stability of the test substance in the solvent/vehicle: Stability tests of 2-mercaptobenzimidazole in DMSO solution were carried out at low concentration (3.125 mg / ml) in this study and high concentration (300 mg / ml) in chromosomal aberration test conducted simultaneously in our laboratory 2 concentration under light-shielded condition at room temperature. As a result, the average content of each 3 samples after preparation for 4 hours was 99.7 and 108% with respect to the average of the initial value (0 hour), respectively. In addition, as a result of conducting the content measurement test on the prepared specimens used in this Test I, the content of the 3.125 mg / ml solution was 96.2 to 97.1% with respect to the predetermined concentration, the content of the 50 mg / ml solution was 95.4 to 96.2% there were.
From the above results, it was confirmed that the 2-mercaptobenzimidazole was stable in the DMSO solution and the content of the test substance in the preparation solution was within the predetermined value range.
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium: No data

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: 2-Mercaptobenzimidazole was prepared by adjusting the concentration to 50 mg / ml in dimethylsulfoxide (hereinafter abbreviated as DMSO, Wako Pure Chemical Industries, Ltd.), then further diluting it with the same solvent at a common ratio of 2 to about 3 was used for the test promptly.

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation:10 to 12 weeks
- Weight at study initiation: 2.0kg±200g
- Housing: Animals were housed individually in stainless steel cages provided with stainless steel mesh bottom and facilities for food and water bottle.
- Diet (e.g. ad libitum): Pelleted feed,ad libitum
- Water (e.g. ad libitum): Community tap water passed through ‘Aqua Guard on line water filter’, was kept in glass bottles, ad libitum
- Acclimation period: The healthy rabbits selected for study was acclimatized to standard laboratory condition for one week in experimental room under Veterinary examination.

ENVIRONMENTAL CONDITIONS
- Temperature (°C):22-25 deg.C
- Humidity (%):40-60%
- Air changes (per hr):10-15 air changes per hour
- Photoperiod (hrs dark / hrs light):12 hours artificial fluorescent light and 12 hours dark.

Test system

Type of coverage:
open
Preparation of test site:
shaved
Vehicle:
not specified
Controls:
not specified
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit):0.5 gm
Duration of treatment / exposure:
4 hour
Observation period:
14 days
Number of animals:
Three female rabbits
Details on study design:
TEST SITE
Initial test
Area of exposure: The test compound in the amount of 0.5 gm was applied at the different sites on the shaven back skin of animal.
- % coverage: Approximately 6 cm2.
- Type of wrap if used: Adhesive tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): No data available
- Time after start of exposure:No data available

OBSERVATION TIME POINTS
(indicate if minutes, hours or days) 3 min ,1 hour ,4 hour,24,48 and 72 hours

SCORING SYSTEM:
- Method of calculation

Confirmatory test;
- Area of exposure:The test compound in the amount of 0.5 gm was applied at the different sites on the shaven back skin of animal.
- % coverage:Approximately 6 cm2.
- Type of wrap if used: Adhesive tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Cleaned with lukewarm water.
- Time after start of exposure: 4 hour

OBSERVATION TIME POINTS
(indicate if minutes, hours or days) ; 60 min ,24,48 and 72 hours

SCORING SYSTEM: Draize’s method.TEST SITE
:

Results and discussion

In vivo

Results
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
14 d
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
The test chemical applied at the dose level of 0.5 gm on shaven back skin of rabbit did not produced any irritation to skin during the period of observation.
Other effects:
Clinical Signs: The test chemical when applied on the shaven back skin of rabbit in the amount of 0.5 gm did not produce any clinical signs of toxicity throughout the examination period of 14 days.

Any other information on results incl. tables

INDIVIDUAL ANIMAL DERMAL IRRITATION SCORES

 

Rabbit No.

Sex

INTACT SKIN

3 Min.

4 Hours

24 Hours

48 Hours

72 Hours

14 days

Erythema

Oedema

Erythema

Oedema

Erythema

Oedema

Erythema

Oedema

Erythema

Oedema

Erythema

Oedema

01

F

0

0

0

0

0

0

0

0

0

0

0

0

02

F

-

-

0

0

0

0

0

0

0

0

0

0

03

F

-

-

0

0

0

0

0

0

0

0

0

0

Total

0

0

0

0

0

0

0

0

0

0

0

0

Mean

0

0

0

0

0

0

0

0

0

0

0

0

Grand Total

0.00

 

Dermal Irritation Index: 0.0/4 = 0.0

Table 2:

CLINICAL SIGNS

 

SEX

ANIMAL NO.

Time (Min.)

Time (Hours)

Time (Day)

3

1

4

24

48

72

14

 

FEMALE

 

01

N

N

N

N

N

N

N

02

N

N

N

N

N

N

N

03

N

N

N

N

N

N

N

 

N: No Clinical Signs

C: Clinical Signs Observed

Applicant's summary and conclusion

Interpretation of results:
other: not irritating
Conclusions:
The dermal irritation index of New Zealand white rabbits is calculated as 0.00 and test compound can be classified under non irritant categorie s. Thus based on result obtained from present experimentation, it can be concluded that the test compound was non irritant to skin of the New Zealand white under test conditions.
Executive summary:

The test compound was tested for its dermal irritation potential in New Zealand White Rabbits according to guideline OECD-404.

In the initial test one healthy rabbit of body weight 2.24 kg selected for study after acclimatization. The test compound in the amount of 0.5 gm was applied at the different sites on the shaven back skin of animal. The hairs of back sides were removed (approximately 6 cm2) with the help of electric clipper one day earlier before the treatment. Animal was also observed for any dermal irritation or skin related infection at the site of application one day earlier.

The site of application was covered with impervious dressing secured in position with adhesive tape. The first patch was applied on the shaven back skin of rabbit and removed after three minutes. No serious reaction was observed at the site of application. The second patch was applied on the different shaven back side and removed after one hour. There were no signs of skin reaction observed at this site of application. Finally, a third patch was applied at a different site and was removed after four hour. No skin reaction was observed at the site of application of test compound. Finally, the animal was observed for 14 days, for any irritation and corrosion. Because no corrosive effect was observed in the initial test, a confirmatory test was done using two additional animals. In the confirmatory test the test compound in the amount of 0.5 gm was applied on the shaven back skin of two animals (body weight ranges 2.14 and 2.09 kg), each with one patch, for an exposure period of four hours.

After four hours the patch was removed and the skin reactions were graded according to Draize’s method. The test chemical in the amount of 0.5 gm did not produce any dermal irritation in terms of erythema or edema in any of the animals after the four hours application. Both the animals were also free from any clinical signs of toxicity throughout the observation period of 14 days. The dermal irritation index of New Zealand white rabbits is calculated as 0.00 and test compound can be classified under non irritant categorie s. Thus based on result obtained from present experimentation, it can be concluded that the test compound was non irritant to skin of the New Zealand white under test conditions.

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