Registration Dossier

Skin Irritation

A study was performed to determine the highest irritant or non-irritant concentration of the test chemical which is to be used for the Open Epicutaneous test (OET)

Skin irritation was observed in the test animals at all concentrations after 21 days of repeated application of the test chemical.

The lowest irritant concentration was observed to be 3% test chemical in acetone and highest irritant 10% in test chemical.

Based on these observations, the test chemical can be considered to be irritating to skin.

Eye Irritation

Based on the available data for the various test chemicals and applying the weight of evidence approach, it can be concluded that the test chemical will also behave in similar manner and was estimated to be not irritating to eyes. Thus it can be further classified under the category “Not Classified” as per CLP regulation.

Reference

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:

comparable to guideline study with acceptable restrictions

Justification for type of information:

data is from experimental reports

Qualifier:

according to guideline

Guideline:

other: Open Epicutaneous test (OET)

Principles of method if other than guideline:

To determine the highest irritant or non-irritant concentration of the test chemical which is to be used for the Open Epicutaneous test (OET)

GLP compliance:

not specified

Species:

guinea pig

Strain:

not specified

Type of coverage:

open

Preparation of test site:

other: clipped flank

Vehicle:

other: acetone

Controls:

yes

Amount / concentration applied:

60, 30, 10 and 3 %

Duration of treatment / exposure:

21 days

Observation period:

after a single application or after repeated application over 21 successive days

Number of animals:

6-8

Details on study design:

One day before starting the induction procedure, the threshold-toxic concentration of the test material is estimated. A single application of 0.025 ml of each test concentration (e.g. 100, 30, 10 and 3%) is simultaneously performed on one of the areas measuring 2cm2 of the flank skin previously clipped and marked with a circular stamp.
The skin reactions are read 24 hours after the application of the test material. The minimal irritant and the maximal non-irritant concentrations are determined by an all-or-none criterion. The minimal irritant concentration is defined as the lowest one causing skin irritation. The maximal non-irritant concentration is defined as the highest one not causing macroscopic skin reactions in any of the animals. The estimation of the threshold concentration (minimal irritating and maximal non-irritating concentrations) is essential for the evaluation of the allergenic capacity of the test material based on the end point determination.

Irritation parameter:

other: Highest non irritant

Basis:

mean

Time point:

24 h

Reversibility:

not specified

Remarks on result:

positive indication of irritation

Remarks:

3% solution of the substance

Irritation parameter:

other: Lowest irritant

Basis:

mean

Time point:

24 h

Reversibility:

not specified

Remarks on result:

positive indication of irritation

Remarks:

10% solution of the substance

Irritant / corrosive response data:

Skin irritation was observed in the test animals at all concentrations after 21 days of repeated application of the test chemical.
The lowest irritant concentration was observed to be 3% test chemical in acetone and highest irritant 10% in test chemical

After repeated application over 21 successive days

Concentration %	Skin irritation after days
Concentration %	7	14	21
60	(+)	+	+
30	(+)	+	+
10	(+)	(+)	(+)
3	-	(+)	(+)

Degree of skin irritation:

- = none

(+) = very slight

+ = slight

++ = moderate

+++ = strong

++++ = very strong

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Conclusions:

Skin irritation was observed in the test animals at all concentrations after 21 days of repeated application of the test chemical.
The lowest irritant concentration was observed to be 3% test chemical in acetone and highest irritant 10% in test chemical.
Based on these observations, the test chemical can be considered to be irritating to skin

Executive summary:

A study was performed to determine the highest irritant or non-irritant concentration of the test chemical which is to be used for the Open Epicutaneous test (OET)

Skin irritation was observed in the test animals at all concentrations after 21 days of repeated application of the test chemical.

The lowest irritant concentration was observed to be 3% test chemical in acetone and highest irritant 10% in test chemical.

Based on these observations, the test chemical can be considered to be irritating to skin

Endpoint conclusion:

adverse effect observed (irritating)

Reference

Endpoint:

eye irritation: in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Remarks:

Weight of evidence approach based on various test chemicals

Justification for type of information:

Weight of evidence approach based on various test chemicals

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

other: Weight of evidence approach based on various test chemicals

Principles of method if other than guideline:

Weight of evidence approach based on various test chemicals. The study 2,3 are referred as study 1,2

GLP compliance:

not specified

Species:

rabbit

Strain:

not specified

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

1. 0.1 ml
2. 0.1 ml

Duration of treatment / exposure:

single

Observation period (in vivo):

1. 24, 48 and 72 hours
2. 1, 24, 48 and 72 h.

Duration of post- treatment incubation (in vitro):

no data available

Number of animals or in vitro replicates:

1. 3
2. 4

Irritation parameter:

overall irritation score

Basis:

mean

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:

Based on the available data for the various test chemicals and applying the weight of evidence approach, it can be concluded that the test chemical will also behave in similar manner and was estimated to be not irritating to eyes. Thus it can be further classified under the category “Not Classified” as per CLP regulation.

Executive summary:

The ocular irritation potential of the test chemical was assessed based on the available results from the various test chemicals.

Acute eye irritation study was carried out to assess the toxicity of the test chemical in rabbits. The study was performed according to the Fed. Reg. 38, No. 187, § 1500.42 Guidelines.

0.1 ml test chemical was instilled into the eyes of 3 Vienna White rabbits, and the untreated eye served as control. The treated eyes remained unwashed throughout the test. The treated eyes were graded according to Draize scale for opacity corneal, iritis, redness, chemosis, discharge at 24, 48 and 72 hours post instillation.

Moderate discharge was observed 1 h and slight discharge was observed 24 h after application in 3/3 animals. These effects were fully reversible by 72 hours.

The test substance is considered to be non irritating to the eye. According to the conditions of the test, the test substance does not fullfil the criteria of 67/548/EEC and GHS UN for classification, respectively.

This is supported by the results of the other ocular irritation study performed in four female SPF albino rabbits for test chemical in order to determine the rritancy potency of the test chemical.

A 0.1 ml aliquot of undiluted test chemical was instilled into the left eye then gently closed for 1 s. The untreated right eye of each animal served as a control. Observations were made at 1, 24, 48 and 72 h. Slight to moderate conjunctive irritation (4/4) was observed 1 hour after application. All effects were reversible within 48 h.

As all the observed effects were not persisted after 48 hours, the test chemical was considered to be not irritating in four female SPF albino rabbits.

Based on the available data for the various test chemicals and applying the weight of evidence approach, it can be concluded that the test chemical will also behave in similar manner and was estimated to be not irritating to eyes. Thus it can be further classified under the category “Not Classified” as per CLP regulation.

Endpoint conclusion:

no adverse effect observed (not irritating)

Endpoint conclusion:

no study available

Skin Irritation

Various studies has been reviewed to determine the dermal irritation potential of the test chemical in living organisms. These include experimental in vivo experimental studies performed on guinea pigs, rabbits, humans for the test chemical.

A study was performed to determine the highest irritant or non-irritant concentration of the test chemical which is to be used for the Open Epicutaneous test (OET)

Skin irritation was observed in the test animals at all concentrations after 21 days of repeated application of the test chemical.

The lowest irritant concentration was observed to be 3% test chemical in acetone and highest irritant 10% in test chemical.

Based on these observations, the test chemical can be considered to be irritating to skin.

This is supported by the results of the Standard Draize test performed to determine the irritation potential of the test chemical. Six rabbits were tested with intact skin and six with abraded skin.

500 mg of the test chemical caused well defined erythema and slight edema after 24 hours of exposure

Hence, the test chemical can be considered to be irritating to skin.

These results are supported by a pre-screen for a human maximization study, 5% test chemical in petrolatum (3450 microgram/cm2) was applied to the skin of human volunteers and observed for signs of irritation till 48 hours.

5% test chemical in petrolatum (3450 microgram/cm2) failed to cause irritation to human skin after 48 hours exposure.

Hence, the test chemical can be considered to be not irritating to skin.

For the same chemical, in a patch test study utilizing closed patches (vehicle not specified; concentration not specified, but between 0.05% and 5%) . Patches were applied under occlusion to the forearm of 465 Japanese Dermatology patients for 24–48 h and scored upon removal.

11 of 465 Japanese dermatology patients had a positive irritation reaction to the test chemical after 48 hours. Hence, the test chemical can be considered to be irritating to skin.

These results are supported by a study to determine the dermal irritation potential of the test chemical was assessed in rabbits.

Administration of the test chemical for 72 hrs to rabbit resulted in moderate irritating on repeated application especially to abraded skin.

Eventough the results of pre-screen test for human maximization test indicate a possibility of the test chemical being not irritating to skin, but the remaining studies suggest otherwise. Also, in the single and repeated exposure of the test chemical to skin, moderate irritation was observed. Taking into consideration, all these parameters, the test chemical can be considered to be irritating to skin. Comparing the above annotations with the criteria of CLP Regulation, the test chemical can be classified under the category “Category 2”.