1,3-dihydro-5-methoxy-2H-benzimidazole-2-thione

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

Data from experimental study report.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2014

Report date:

2014

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Principles of method if other than guideline:

Acute Dermal Irritation/Corrosion study of test chemical was performed in Rabbits

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Methyl 2-naphthyl ether

EC Number:

202-213-6

EC Name:

Methyl 2-naphthyl ether

Cas Number:

93-04-9

Molecular formula:

C11H10O

IUPAC Name:

2-methoxynaphthalene

Test material form:

solid

Details on test material:

- Name of test material (as cited in study report): Methyl 2-naphthyl ether
- Molecular formula :C11H10O
- Molecular weight :158.19 g/mol
- Substance type: Organic
- Physical State: Solid

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: LIVEON BIOLABS PVT LTD
- Age at study initiation: 2.5 to 3.5 Months (Approximately)
- Weight at study initiation: Minimum: 1.624 kg & Maximum: 2.100 kg (Prior to Treatment)
- Housing:
Husbandry : The animals were housed individually in stainless steel cages.
Room Sanitation : The experimental room floor and work tops were swept and mopped with disinfectant solution every day.
Cages and water bottle : All the cages and water bottles were changed minimum twice a week.
- Diet (e.g. ad libitum): All animals were provided conventional laboratory rabbit diet ad libitum
- Water (e.g. ad libitum): Aqua guard filtered tap water was provided ad libitum
- Acclimation period: Rabbits were acclimatised to the test conditions for a period of 6 days (Animal No.-1) and 8 days (Animal No.-2 and 3) prior to the application of the test item.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Minimum: 20.30 °C Maximum: 22.70 °C
- Humidity (%): Minimum: 48.30 % Maximum: 68.30 %
- Air changes (per hr): More than 12 changes per hour
- Photoperiod (hrs dark / hrs light): 12:12

Test system

Type of coverage:

occlusive

Preparation of test site:

clipped

Vehicle:

water

Controls:

yes, concurrent vehicle

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 500 mg moistened with 0.5 ml distilled water


VEHICLE
- Amount(s) applied (volume or weight with unit): 0.5 ml
- Concentration (if solution):no data
- Lot/batch no. (if required): no data
- Purity: no data

Duration of treatment / exposure:

4-hour exposure period

Observation period:

72 hours

Number of animals:

Three of each sex

Details on study design:

TEST SITE
- Area of exposure: dorsal lumbar region at contralateral sites
- % coverage: approximately 6 X 6 cm
- Type of wrap if used: porous gauze dressing and non-irritating tape (Micropore 3”)

REMOVAL OF TEST SUBSTANCE
- Washing (if done): test substance was removed by using cotton soaked in distilled water
- Time after start of exposure: 4 hrs

SCORING SYSTEM: Grading of irritation lesions was carried out as per Draize Method

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

mean

Remarks:

Animal 1,2,3

Time point:

other: 24, 48 and 72 hours

Score:

0.33

Max. score:

3

Reversibility:

no data

Remarks on result:

other: not irritating

Results 2

Irritation parameter:

edema score

Basis:

mean

Remarks:

Animal 1,2 and 3

Time point:

other: 24, 48 and 72 hours

Score:

0

Max. score:

3

Reversibility:

no data

Remarks on result:

other: not irritating

Irritant / corrosive response data:

Animal No. 1, showed very slight erythema (barely perceptible) and no oedema observed at 1 hour of observation. At 24, 48 and 72 hour observation no erythema and oedema was observed in animal No 1.
In Animals No. 2 and 3 at 1 hour observation post patch removal, revealed very slight erythema (barely perceptible) and no oedema. At 24 hour animal no. 2 showed no erythema and oedema whereas animal no. 3 revealed very slight erythema (barely perceptible) and no oedema. At 48 and 72 hour post patch removal, both the animals recovered to normal.

Other effects:

Clinical Observation
No systemic toxicity was observed at treated rabbits during the experimental period.

Mortality
No mortality was observed during the observation period.

Body weights
Body weights were increased as compared to day 0 in all the three animals.

Any other information on results incl. tables

Table 1

Skin Reaction

 

In Treated area Dose:500 mg of test item (moistened with 0.5 ml distilled water)           Sex:Male

 

Animal No.	Test	Treated  area*	Erythema score				Oedema score
			1h	24h	48h	72h	1h	24h	48h	72h
1	Initial	Left	1	0	0	0	0	0	0	0
2	Confirmatory	Left	1	0	0	0	0	0	0	0
3		Left	1	1	0	0	0	0	0	0

 

 

In Control areaDose:0.5 ml of distilled water                                                          Sex:Male

 

Animal No.	Test	Treated area*	Erythema score				Oedema score
			1h	24h	48h	72h	1h	24h	48h	72h
1	Initial	Right	0	0	0	0	0	0	0	0
2	Confirmatory	Right	0	0	0	0	0	0	0	0
3		Right	0	0	0	0	0	0	0	0

Key: h = Hour.

Erythema                                                                                                       Oedema

0 =No erythema                                                                                           0 =No oedema

1 = Very slight erythema(barely perceptible)

Table 1 Continued…

Mean Individual Animal Score at 24, 48 and 72 hours

 

Animal Number                   Observations	1	2	3
Erythema	0.00	0.00	0.33
Oedema	0.00	0.00	0.00

Table 2

Individual Animal BodyWeight

Sex:Male

Animal No.	Body Weight (kg)
	Prior to Dosing	At termination
1	1.624	1.718
2	2.100	2.172
3	1.846	1.922

Table 3

Individual AnimalClinicalSigns

Sex:Male

Animal No.	Days (Post dosing Observation)
	0	1	2	3
1	1	1	1	1
2	1	1	1	1
3	1	1	1	1

Key: ./. = Not Applicable. 1 = Normal.

Applicant's summary and conclusion

Interpretation of results:

other: not irritating

Conclusions:

No erythema and oedema (skin irritation) were observed at the end of 72 hour observation period after patch removal. Hence, test chemical was considered to be Non-Irritating to the skin of male New Zealand White rabbits under the experimental conditions tested

Executive summary:

Acute Dermal Irritation/corrosion Study of test chemical was performed as per OECD guideline No. 404.Three healthy young adult male rabbits were used for the study. The hairs of all the rabbits were clipped at contralateral sites, approximately 24 hours prior to treatment.A dose of 500 mgof test item (moistened with 0.5 ml distilled water) was applied to the skin,over an area of approximately 6 x 6 cm clippedof hair on one side of rabbits.The other untreated side was kept as control area and 0.5 ml of distilled water was applied at this site. At the end of 4 hours, the gauze patch was removed and test item application site was wiped with water. Initially, the test item was applied to the clipped area of skin of one rabbit. The test site was covered with gauze patch.After 4 hours of exposure in animal no. 1,very slight erythema (barely perceptible) and no oedema observed at 1 hour of observation. At 24, 48 and 72 hours observation no erythema and oedema was observed in animal no 1.Hence the confirmatory test was conducted on additional two rabbits (No. 2 and 3)to confirm the non irritant nature of the test item. The patch was removed after 4 hours and rabbits wereobservedfor erythema and oedemaat 1, 24, 48 and 72 hours after patch removal, evaluatedand graded as per draize method. In animal no. 2 and 3 at 1 hour observation post patch removal, revealed very slight erythema (barely perceptible) and no oedema. At 24 hour animal no. 2 showed no erythema and oedema whereas animal no. 3 revealed very slight erythema (barely perceptible) and no oedema, At 48 and 72 hour post patch removal, both the animals recovered to normal. The individual mean score at 24, 48 and 72 hours for animal nos. 1, 2 and 3 were 0.00, 0.00, 0.33 and 0.00, 0.00, 0.00, for erythema and oedema formation, respectively. Hence, test chemical was considered to be Non-Irritating to the skin of male New Zealand White rabbits under the experimental conditions tested.