Registration Dossier

Skin Irritation:

The primary skin irritant / Corrosion effects was on rabbits (Inner surface of the ears) tested. The overall score for erythema and edema formation after 7 days was 0.0 Following the EC Guideline for the Classification and Labeling of Hazardous Substances and Preparations (July 1983), the test chemical can to be considered as non-irritating to the skin.

Eye Irritation:

For the assessment of the eye irritation values, the corresponding stimulus values from the DRAIZE grades were determined at the assessment times 24, 48 and 72 hours, taking into account the type, intensity and temporal course of the findings. No signs of irritation were observed in the rabbit eyes. Following the EC Guideline on the Classification and Labeling of Hazardous Substances and Preparations (July 1983), the test chemical was to be regarded as non-irritating to the eyes.

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Justification for type of information:

data is from experimental reports

Qualifier:

according to guideline

Guideline:

other: as mentioned below

Principles of method if other than guideline:

To assess the dermal irritation potential of the test chemical in New Zealand White rabbits

GLP compliance:

not specified

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Sex: male and female
- Source: no data available
- Age at study initiation:
- Weight at study initiation: 2.5 to 3.4 kg
- Housing: The animals were conventionally kept in single cages under standardized conditions
- Diet (e.g. ad libitum): The diet consisted of a standard diet, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period:no data available

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25 ° C
- Humidity (%): 40-60%
- Photoperiod (hrs dark / hrs light):dark-light rhythm of 12 hour

Type of coverage:

occlusive

Preparation of test site:

not specified

Vehicle:

not specified

Controls:

not specified

Amount / concentration applied:

0.5g

Duration of treatment / exposure:

24 hours

Observation period:

0,24,48,72hours, 7 and 14 days

Number of animals:

2

Details on study design:

TEST SITE
- Area of exposure: back of the ear
- % coverage: no data available
- Type of wrap if used: plaster bandages

REMOVAL OF TEST SUBSTANCE
- Washing (if done):
- Time after start of exposure:test sample was washed off with soap and water

OBSERVATION TIME POINTS
(indicate if minutes, hours or days) : 0, 24,48, 72 hours and 7, 14 days

SCORING SYSTEM:
- Method of calculation: The numerical recording of the effects was made by DRAIZE.

Irritation parameter:

erythema score

Basis:

mean

Time point:

14 d

Score:

0

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

mean

Time point:

14 d

Score:

0

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

no erythema or edema observed

Table 1: The animal-specific skin reactions and the skin irritation values are as follows:

Rabbit number	Draize-grade after approximately												stimulus value
	0		24		48		72		7		14		E	(ed)
	E	(ed)	E	(ed)	E	(ed)	E	(ed)	E	(ed)	E	(ed)	E	(ed)
53	0	0	0	0	0	0	0	0	0	0	N	N	0	0
47	0	0	0	0	0	0	0	0	0	0	N	N	0	0

E = erythema / scab; (ED) = edema; N = no assessment

Interpretation of results:

other: not irritating

Conclusions:

The primary skin irritant / Corrosion effects was on rabbits (Inner surface of the ears) tested. The overall score for erythema and edema formation after 7 days was 0.0 Following the EC Guideline for the Classification and Labeling of Hazardous Substances and Preparations (July 1983), the test chemical can to be considered as non-irritating to the skin.

Executive summary:

The dermal irritation potential of the test chemical was assessed in New Zealand White rabbits.2 Albino rabbits (white New Zealand) of both sexes were used with a body weight of about 2.5 to 3.4 kg. The animals were conventionally kept in single cages under standardized conditions.

For the treatment of each animal, 0.5 g of the test sample was applied to a pulp pad and fixed to the hairless inside of a rabbit of 2 rabbits by means of plaster bandages. To better support the patch, a Stilck pulp was formed into a roll and tied into the ear. The exposure duration was 24 hours. Then the test sample was washed off with soap and water. Erythema and edema were observed and scored at 0, 24,48, 72 hours and 7, 14 days. The numerical recording of the effects was made according to DRAIZE.

The primary skin irritant / Corrosion effects was on rabbits (Inner surface of the ears) tested. The overall score for erythema and edema formation after 7 days was 0.0 Following the EC Guideline for the Classification and Labeling of Hazardous Substances and Preparations (July 1983), the test chemical can to be considered as non-irritating to the skin.

Endpoint conclusion:

no adverse effect observed (not irritating)

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Justification for type of information:

data is from experimental reports

Qualifier:

according to guideline

Guideline:

other: as mentioned below

Principles of method if other than guideline:

To assess the ocular irritation potential of the test chemical in New Zealand white rabbits

GLP compliance:

not specified

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Sex: male and female
- Source: no data available
- Age at study initiation:
- Weight at study initiation: 2.5 to 3.4 kg
- Housing: The animals were conventionally kept in single cages under standardized conditions
- Diet (e.g. ad libitum): The diet consisted of a standard diet, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period:no data available

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25 ° C
- Humidity (%): 40-60%
- Photoperiod (hrs dark / hrs light):dark-light rhythm of 12 hour

Vehicle:

not specified

Controls:

not specified

Amount / concentration applied:

no data available

Duration of treatment / exposure:

no data available

Observation period (in vivo):

0, 24,48,72 hours and 7 and 14 days

Duration of post- treatment incubation (in vitro):

no data available

Number of animals or in vitro replicates:

2

Details on study design:

SCORING SYSTEM: DRAIZE method of scoring

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

24/48 h

Score:

0

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

No signs of irritation observed

Interpretation of results:

other: not irritating

Conclusions:

For the assessment of the eye irritation values, the corresponding stimulus values from the DRAIZE grades were determined at the assessment times 24, 48 and 72 hours, taking into account the type, intensity and temporal course of the findings. No signs of irritation were observed in the rabbit eyes. Following the EC Guideline on the Classification and Labeling of Hazardous Substances and Preparations (July 1983), the test chemical was to be regarded as non-irritating to the eyes.

Executive summary:

The ocular irritation potential of the test chemical was assessed in New Zealand white rabbits.

2 Albino rabbits (white New Zealand) of both sexes were used with a body weight of about 2.5 to 3.4 kg. The animals were conventionally kept in single cages under standardized conditions. The test chemical was instilled in the eyes of the rabbits and observed for signs of irritation(dose not mentioned).

The eye reactions were observed and scored at 0, 24,48, 72 hours and 7, 14 days. The numerical recording of the effects was made according to DRAIZE.

For the assessment of the eye irritation values, the corresponding stimulus values from the DRAIZE grades were determined at the assessment times 24, 48 and 72 hours, taking into account the type, intensity and temporal course of the findings. No signs of irritation were observed in the rabbit eyes. Following the EC Guideline on the Classification and Labeling of Hazardous Substances and Preparations (July 1983), the test chemical was to be regarded as non-irritating to the eyes.

Endpoint conclusion:

no adverse effect observed (not irritating)

Endpoint conclusion:

no study available

Skin Irritation

Various studies have been reviewed to determine the level of dermal irritation caused by the test chemical in living organisms. The results include in vivo experimental data on rabbits, rats for the test chemical. The studies are summarized as follows:

The dermal irritation potential of the test chemical was assessed in New Zealand White rabbits.2 Albino rabbits (white New Zealand) of both sexes were used with a body weight of about

2.5 to 3.4 kg. The animals were conventionally kept in single cages under standardized conditions.

For the treatment of each animal, 0.5 g of the test sample was applied to a pulp pad and fixed to the hairless inside of a rabbit of 2 rabbits by means of plaster bandages. To better support the patch, a Stilck pulp was formed into a roll and tied into the ear. The exposure duration was 24 hours. Then the test sample was washed off with soap and water. Erythema and edema were observed and scored at 0, 24,48, 72 hours and 7, 14 days. The numerical recording of the effects was made according to DRAIZE.

The primary skin irritant / Corrosion effects was on rabbits (Inner surface of the ears) tested. The overall score for erythema and edema formation after 7 days was 0.0 Following the EC Guideline for the Classification and Labeling of Hazardous Substances and Preparations (July 1983), the test chemical can to be considered as non-irritating to the skin.

This is supported by a study which was designed and conducted to determine the dermal reaction profile of the test chemical in Sprague Dawley rats. The study was performed as per OECD Guidelines 402 and complying to the GLP procedures.

5 female young adult, non-pregnant rats were used for the study. The animals were kept in their cages for at least 5 days prior to administration for acclimatization to the laboratory condition and after acclimatization period, animals were randomly selected. Approximately 24 hours before application, the hair of each rat was closely clipped from the trunk (dorsal surface and sides from scapular to pelvic area) with an electric clipper, so as to expose at least 10% of the body surface area. The test item was applied directly onto the exposed skin of the animal, taking care

to spread the test item evenly over the entire area of approximately 10% of the total body surface area or as much of the area as can reasonably be covered. The test item was held in contact with the skin using a porous gauze dressing and non irritating tape around the animal to cover the exposure site for first 24 hours exposure period. Elizabethan collar was placed on each animal for first 24 hours after application of the test item. These collars prevent ingestion of test item. Following 24 hours of exposure, the wrapping was removed and the test site wiped free of excess test item. Distilled water was used to remove residual test item.

A single dose of 200 mg/kg, 1000 mg/kg and 2000 mg/kg body weight of the test item were applied to 1 female animal respectively in the dose range finding study. Since no signs of irritation were observed at the maximum dose of 2000 mg/kg in the test animals, 2 additional animals were tested in the main study with 2000 mg/kg. The animals were applied with a dose of 2000 mg/kg body weight in sequential manner at 48 hours intervals. Dermal reaction was observed daily for study period of 14 days.

The overall irritation score of the substance was determined to be 0 and no erythema and edema (skin irritation) were found at the end of 14 days observation period after patch removal.

Hence, it was concluded that the test chemical was Non-Irritating to the skin of female Sprague Dawley rats under the experimental conditions tested and classified as “Category- Not Classified” as per CLP Classification.

Based on the available results, it can be considered that the test chemical certainly lacks the potential to cause irritation to skin. Hence, it can be considered to be not irritating to skin. Comparing the above annotations with the criteria of CLP Regulation, the test chemical can be classified under the category “Not Classified”.

Eye Irritation:

The ocular irritation potential of the test chemical was assessed in New Zealand white rabbits.

2 Albino rabbits (white New Zealand) of both sexes were used with a body weight of about 2.5 to 3.4 kg. The animals were conventionally kept in single cages under standardized conditions. The test chemical was instilled in the eyes of the rabbits and observed for signs of irritation(dose not mentioned).

The eye reactions were observed and scored at 0, 24,48, 72 hours and 7, 14 days. The numerical recording of the effects was made according to DRAIZE.

For the assessment of the eye irritation values, the corresponding stimulus values from the DRAIZE grades were determined at the assessment times 24, 48 and 72 hours, taking into account the type, intensity and temporal course of the findings. No signs of irritation were observed in the rabbit eyes. Following the EC Guideline on the Classification and Labeling of Hazardous Substances and Preparations (July 1983), the test chemical was to be regarded as non-irritating to the eyes.

Based on the available result, it can be considered that the test chemical certainly lacks the potential to cause irritation to eyes. Hence, it can be considered to be not irritating to eyes. Comparing the above annotations with the criteria of CLP Regulation, the test chemical can be classified under the category “Not Classified”.

Available studies for the test chemical indicate a possibility that the test chemical lacks the potential to cause irritation to eyes and skin.

Hence, the test chemical can be considered to be not irritating to eyes and skin. It can be further classified under the category "Not Classified" as per CLP Regulation.