Registration Dossier

Administrative data

Description of key information

Skin Irritation:

The dermal irritation potential of test chemical was assessed in various experimental studies conducted on rabbits. Based on the available data for the key and supporting studies, it can be concluded that the test chemical is unable to cause skin irritation and thus considered as not irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

Eye irritation:

An ocular irritation potential of target chemical was assessed in various experimental studies conducted on test animals. Based on the available data for the key and supporting studies, it can be concluded that the test chemical is not able to cause eye irritation and thus can be considered as not irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not classified (Not irritating)”.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
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:
data from handbook or collection of data
Justification for type of information:
data is from peer reviewed journals
Qualifier:
according to
Guideline:
other: as mentioned below
Principles of method if other than guideline:
The test uses a single rabbit ear to indicate the Comedogenicity and irritancy of test chemical.
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
Source: No data
Age at study initiation: No data
Weight at study initiation: 3 kg
Fasting period before study: No data
Housing: singly housed, in suspended cages
Diet (e.g. ad libitum): Purina Rabbit Chow, ad libitum
Water (e.g. ad libitum): water, ad libitum
Acclimation period: No data

ENVIRONMENTAL CONDITIONS
Temperature (°C): No data
Humidity (%):No data
Air changes (per hr): No data
Photoperiod (hrs dark / hrs light): 12 hour light and 12 hr dark cycle

IN-LIFE DATES: From: No data To: No data
Type of coverage:
open
Preparation of test site:
not specified
Vehicle:
other: propylene glycol
Controls:
yes
Amount / concentration applied:
Dose of 1ml of the test material was applied once daily for five days per week for 2 weeks.
Duration of treatment / exposure:
once daily five days per week for two weeks
Observation period:
no data available
Number of animals:
3
Details on study design:
TEST SITE
Area of exposure: Ear
% coverage: A dose of 1ml of the test chemical is applied and spread once daily to the entire inner surface of one ear five days per week for 2 weeks.
Type of wrap if used: No data

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

SCORING SYSTEM: The irritancy produced by repeated application of a chemical or skin care product on the surface epidermis in the rabbit ear is evaluated on a scale of 0 to 5. The grades are summarized as follows:
0 = No irritation
1 = few scales, no Erythema
2 = diffuse scaling, no Erythema
3 = Generalized scaling with Erythema
4 = Scaling, Erythema and Edema
5 = Epidermal necrosis and slough
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
14 d
Score:
0
Max. score:
5
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
No irritation observed

Table 1: Ingredients and their Comedogenicity and Irritancy

Test chemical

Comedogenicity*

[Grade 0-5]

Irritancy**

[Grade 0-5]

2

0

 

*Comedogenicity or the ability of test substance to produce follicular hyperkeratosis

** Irritancy or ability of test substance to produce surface epithelial irritation

Interpretation of results:
other: not irritating
Conclusions:
The test uses a single rabbit ear to indicate the Comedogenicity and irritancy of test chemical. The irritancy produced by test chemical was graded from 0 – 5. It falls under Grade 0 (no irritation observed). Hence it can be concluded that test chemical was not irritating to rabbit ears.
Executive summary:

The test uses a single rabbit ear to indicate the Comedogenicity and irritancy of test chemical. The test chemical was mixed in propylene glycol at a 9 to 1 dilution for testing unless otherwise indicated (10% concentration). A colony of New Zealand White albino rabbits that have genetically good ears and free from mites were used. Three rabbits, weighing two to three kilograms, were used for each assay. Animals were housed singly in suspended cages and fed Purina Rabbit Chow and water ad libitum. Animals were maintained on a 12-hour light and 12-hour dark cycle. A dose of 1 ml of the test material was applied and spread once daily to the entire inner surface of once for five days per week for two weeks. The opposite untreated ear of each animal served as an untreated control.

The irritancy produced by repeated application of the chemical on the surface epidermis in the rabbit ear is evaluated on a scale of 0 to 5. The grades are summarized as follows:

 0 = No irritation; 1 = few scales, no Erythema; 2 = diffuse scaling, no Erythema; 3 = Generalized scaling with Erythema; 4 = Scaling, Erythema and Edema; 5 = Epidermal necrosis and slough.

Test chemical falls under Grade 0 (no irritation observed).

Hence it can be concluded that the test chemical was not irritating to rabbit ears.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin Irritation (In-vivo):

Various studies were performed on rabbits and rats to assess the dermal irritation potential of test chemical which have been summarized as follows:

The test uses a single rabbit ear to indicate the Comedogenicity and irritancy of test chemical. The test chemical was mixed in propylene glycol at a 9 to 1 dilution for testing unless otherwise indicated (10% concentration). A colony of New Zealand White albino rabbits that have genetically good ears and free from mites were used. Three rabbits, weighing two to three kilograms, were used for each assay. Animals were housed singly in suspended cages and fed Purina Rabbit Chow and water ad libitum. Animals were maintained on a 12-hour light and 12-hour dark cycle. A dose of 1 ml of the test material was applied and spread once daily to the entire inner surface of once for five days per week for two weeks. The opposite untreated ear of each animal served as an untreated control.The irritancy produced by repeated application of the chemical on the surface epidermis in the rabbit ear is evaluated on a scale of 0 to 5.Test chemical falls under Grade 0 (no irritation observed).Hence it can be concluded that the test chemical was not irritating to rabbit ears.Thus, based on above observations, the test chemical be determined as "Not irritating" to skin of rabbits.

Two dermal irritation studies were designed and conducted to determine the dermal reaction of test chemical in Sprague Dawley rats. The test item was applied to shorn skin of 5 male and 5 female animals at 2000 mg/kg body weight. Administration of the test item at 2000 mg/kg did not result in any skin reaction at the site of application during the study period of 14 days. Administration of the test item did not result in any signs of toxicity and mortality during the study period of 14 days. Animals exhibited normal body weight gain through the study period of 14 days. Gross pathological examination did not reveal any abnormalities attributable to the treatment. The overall irritation score of the substance was determined to be 0 and no erythema and edema (skin irritation) the end of 14 days observation period after patch removal. Hence, it was concluded that the substance is non-Irritating to the skin of rats under the experimental conditions tested.

Thus it can be concluded from the above summarized studies that the substance can be classified under the category "Not Classified" as per CLP regulation.

Eye Irritation (In-vivo):

Various studies were performed on test animals to assess the ocular irritation potential of test chemical which have been summarized as follows:

Primary eye irritation study was conducted on male and female New Zealand Albino rabbits to evaluate the irritating nature of the test material.

100 mg/0.1g of the test compound was instilled into one eye each of three young adult rabbits. Scoring of irritation effects was performed approximately 1, 24, 48 and 72 hours, as well as 7 and 10, 14 and 17 days after test item application.The instillation of the test item into the eye resulted in mild to moderate, early-onset and transient ocular changes, such as reddening of the conjunctivae and sclerae, discharge and chemosis. A slight corneal opacity, affecting up to the whole area of the cornea, was also apparent in one animal from 24 hours to 10 days after treatment, A light to marked red staining was also observed in the treated eye of all animals during the first 7 days after treatment. All ocular effects were reversible and were no longer evident 17 days after treatment. No abnormal findings were observed in the iris of any animal at any reading. No corrosion was observed at any of the measuring intervals. Test chemical did not induce significant or irreversible damage to the rabbit eyes. Hence, the test chemical can be considered not irritating to rabbit eyes.

 

 

In another study, primary eye irritation potency was evaluated for the test material in three male rabbits.About 100 mg erythrosine was instilled into the lower conjunctival sac of the right eye. The left eyes of the animals served as controls. 5 minutes after application, the treated eye was washed with 300 ml distilled water and the cornea, iris and conjunctival mucosa of treated eyes were investigated at 12, 24, 48, and 72 hrs after treatment.The test chemical did not cause adverse ocular reactions at 12, 24, 48, and 72 hrs after treatment. Hence the test chemical was considered as not irritating to the eyes of treated rabbits.

The results obtained from these studies lead to a conclusion that Test chemical is indeed not irritating to eye. Hence, comparing the above annotations with the criteria of CLP regulation, Test chemical can be classified under the category “ Not classified based on GHS criteria”.

Justification for classification or non-classification

The skin and eye irritation potential of test chemical were observed in various studies. The results obtained from these studies indicates that the chemical is unlikely to cause skin irritation and eye irritation. Hence the test chemical can be classified under the category “Not Classified” for skin and eye irritation as per CLP.