Registration Dossier

Administrative data

Description of key information

Skin Irritation:

By applying the weight of evidence approach, the test chemical can be considered to be not irritating to skin. Comparing the annotations with criteria of CLP regulation, the test chemical can be classified under the category "Not Classified".

Eye Irritation:

By applying the weight of evidence approach, the test chemical can be considered to be not irritating to skin. Comparing the annotations with criteria of CLP regulation, the test chemical can be classified under the category "Not Classified".

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin 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 chemicals
Justification for type of information:
Weight of evidence approach based on various chemicals
Reason / purpose for cross-reference:
read-across: supporting information
Reason / purpose for cross-reference:
read-across: supporting information
Reason / purpose for cross-reference:
read-across: supporting information
Qualifier:
according to guideline
Guideline:
other: Weight of evidence approach based on various chemicals
Principles of method if other than guideline:
Weight of evidence approach based on various chemicals
GLP compliance:
not specified
Specific details on test material used for the study:
- Name of test material: 2,4-bis[(E)-2-(4-dodecylphenyl)diazen-1-yl]benzene-1,3-diol
- Common name: 2,4-bis[(4-dodecylphenyl)azo]resorcinol
- Molecular formula: C42H62N4O2
- Molecular weight: 654.978 g/mol
- Smiles notation: c1(c(c(c(cc1)\N=N\c1ccc(cc1)CCCCCCCCCCCC)O)\N=N\c1ccc(cc1)CCCCCCCCCCCC)O
- InChl: 1S/C42H62N4O2/c1-3-5-7-9-11-13-15-17-19-21-23-35-25-29-37(30-26-35)43-45-39-33-34-40(47)41(42(39)48)46-44-38-31-27-36(28-32-38)24-22-20-18-16-14-12-10-8-6-4-2/h25-34,47-48H,3-24H2,1-2H3/b45-43+,46-44+
- Substance type: Organic
- Physical state: Solid
Species:
other: rats, rabbits
Strain:
not specified
Type of coverage:
occlusive
Preparation of test site:
clipped
Vehicle:
other: 1,3. undiluted, 2. propylene glycol at a 9 to 1 dilution
Controls:
not specified
Amount / concentration applied:
1. 2000 mg/kg
2. 1ml of test chemical was mixed in propylene glycol at a 9 to 1 dilution for testing unless otherwise indicated (10% concentration)
3. 0.1 ml 5% solution
Duration of treatment / exposure:
1. 24 hours
2. once daily to the entire inner surface of once for five days per week for two weeks
3. single
Observation period:
1. 14 days
2. 14 days
3. 2 days
Number of animals:
1. 5 male and 5 female rats
2. A colony of rabbits
3. no data available
Details on study design:
Weight of evidence approach based on various chemicals
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
14 d
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:
By applying the weight of evidence approach, the test chemical can be considered to be not irritating to skin. Comparing the annotations with criteria of CLP regulation, the test chemical can be classified under the category "Not Classified".
Executive summary:

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

A study 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. Ten rats (5 male and 5 female) were used for conducting dermal irritation /corrosion 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 moistened with distilled water. The test item was applied 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.

The test chemical 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) 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 Sprague Dawley rats under the experimental conditions tested and classified as “Category- Not Classified” as per CLP Classification.

This is supported by the a study performed on a single rabbit ear to indicate the Comedogenicity and irritancy of the 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 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.

The test chemical falls under Grade 0 (no irritation observed).

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

These results are further supported by the irritation potential of the test chemical was assessed in rabbits. Rabbits were given intracutenous injection of 0.1 ml 5% solution of the test chemical on their back skin and observed for signs of dermal reactions (exact duration of study not mentioned). The intracutenous injection did not induce any cutenous damage to the skin. A black spot formed on the on back skin disappeared largely during the second day and was completely invisible after 2 days. Hence, the test chemical can be considered to be not irritating to skin.

By applying the weight of evidence approach, the test chemical can be considered to be not irritating to skin. Comparing the annotations with criteria of CLP regulation, the test chemical can be classified under the category "Not Classified".

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

Eye irritation

Link to relevant study records
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 test chemicals
Justification for type of information:
Weight of evidence approach based on test chemicals
Reason / purpose for cross-reference:
read-across: supporting information
Reason / purpose for cross-reference:
read-across: supporting information
Qualifier:
according to guideline
Guideline:
other: Weight of evidence approach based on test chemicals
Principles of method if other than guideline:
Weight of evidence approach based on test chemicals
GLP compliance:
not specified
Specific details on test material used for the study:
- Name of test material: 2,4-bis[(E)-2-(4-dodecylphenyl)diazen-1-yl]benzene-1,3-diol
- Common name: 2,4-bis[(4-dodecylphenyl)azo]resorcinol
- Molecular formula: C42H62N4O2
- Molecular weight: 654.978 g/mol
- Smiles notation: c1(c(c(c(cc1)\N=N\c1ccc(cc1)CCCCCCCCCCCC)O)\N=N\c1ccc(cc1)CCCCCCCCCCCC)O
- InChl: 1S/C42H62N4O2/c1-3-5-7-9-11-13-15-17-19-21-23-35-25-29-37(30-26-35)43-45-39-33-34-40(47)41(42(39)48)46-44-38-31-27-36(28-32-38)24-22-20-18-16-14-12-10-8-6-4-2/h25-34,47-48H,3-24H2,1-2H3/b45-43+,46-44+
- Substance type: Organic
- Physical state: Solid
Species:
rabbit
Strain:
not specified
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
1. 0.1 ml
2. Undiluted 50 mg
Duration of treatment / exposure:
Single
Observation period (in vivo):
1. 1, 24, 48 and 72 hours
2. 24 hours
Number of animals or in vitro replicates:
1. 3 female
2. no data available
Details on study design:
Weight of evidence approach based on test chemicals
Irritation parameter:
overall irritation score
Basis:
mean
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:
By applying the weight of evidence approach, the test chemical can be considered to be not irritating to eyes. Comparing the annotations with criteria of CLP regulation, the test chemical can be classified under the category "Not Classified".
Executive summary:

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

A study was performed to determine the ocular irritation potential of the test chemical in accordance with OECD 405 Guidelines. 3 female New Zealand White rabbits were used for the study. The test compound in the amount of 0.1 ml applied in the conjunctival sac of one eye of each animal after gentle pulling the lower eye lid away from the eye ball.  The eye lids were then gently held together for about one second to prevent the loss of the material.  The other eyes which remains untreated, served as control.

The eyes of the test animal did not washed for at least 24 hours following instillation of the test compound. At 24 hours a washout may be used if considered appropriate. The eyes were examined at 1, 24, 48 and 72 hours after test substance application. The grades of ocular reaction (conjunctiva, cornea and iris) were recorded at each observation. To determine the reversibility of the effect the animal was observed normally for 21 days. Any other lesions in the eye viz pannus, staining were observed and scored accordingly. Examination of reactions was facilitated by use of biomicroscope and hand slit lamp. After recording the observations at 24 hours, the eyes were further examined with the aid of fluorescein. Individual animal weight before and during the study was also observed

The Modified maximum average score (MMAS) of the test chemical was found to be 8.33.

Based on above results, it can be concluded that the test compound was practically non irritant when applied in the amount of 0.1 gm in the conjunctival sac of the New Zealand White rabbits.

This result is supported by the study performed to assess the eye irritation potential of the test chemical in rabbits.

Undiluted 50 mg of test chemical was instilled in the conjunctival sac of 2 rabbits for 24 hours.

Slight erythema was observed in the rabbit eyes which disappeared in 24 hours. No corneal damage was observed. Hence, the test chemical can be considered to be not irritating to eyes.

By applying the weight of evidence approach, the test chemical can be considered to be not irritating to eyes. Comparing the annotations with criteria of CLP regulation, the test chemical can be classified under the category "Not Classified".

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin Irritation

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

A study 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. Ten rats (5 male and 5 female) were used for conducting dermal irritation /corrosion 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 moistened with distilled water. The test item was applied 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.

The test chemical 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) 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 Sprague Dawley rats under the experimental conditions tested and classified as “Category- Not Classified” as per CLP Classification.

This is supported by the a study performed on a single rabbit ear to indicate the Comedogenicity and irritancy of the 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 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.

The test chemical falls under Grade 0 (no irritation observed).

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

These results are further supported by the irritation potential of the test chemical was assessed in rabbits. Rabbits were given intracutenous injection of 0.1 ml 5% solution of the test chemical on their back skin and observed for signs of dermal reactions (exact duration of study not mentioned). The intracutenous injection did not induce any cutenous damage to the skin. A black spot formed on the on back skin disappeared largely during the second day and was completely invisible after 2 days. Hence, the test chemical can be considered to be not irritating to skin.

By applying the weight of evidence approach, the test chemical can be considered to be not irritating to skin. Comparing the annotations with criteria of CLP regulation, the test chemical can be classified under the category "Not Classified".

Eye Irritation:

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

A study was performed to determine the ocular irritation potential of the test chemical in accordance with OECD 405 Guidelines. 3 female New Zealand White rabbits were used for the study. The test compound in the amount of 0.1 ml applied in the conjunctival sac of one eye of each animal after gentle pulling the lower eye lid away from the eye ball.  The eye lids were then gently held together for about one second to prevent the loss of the material.  The other eyes which remains untreated, served as control.

The eyes of the test animal did not washed for at least 24 hours following instillation of the test compound. At 24 hours a washout may be used if considered appropriate. The eyes were examined at 1, 24, 48 and 72 hours after test substance application. The grades of ocular reaction (conjunctiva, cornea and iris) were recorded at each observation. To determine the reversibility of the effect the animal was observed normally for 21 days. Any other lesions in the eye viz pannus, staining were observed and scored accordingly. Examination of reactions was facilitated by use of biomicroscope and hand slit lamp. After recording the observations at 24 hours, the eyes were further examined with the aid of fluorescein. Individual animal weight before and during the study was also observed

The Modified maximum average score (MMAS) of the test chemical was found to be 8.33.

Based on above results, it can be concluded that the test compound was practically non irritant when applied in the amount of 0.1 gm in the conjunctival sac of the New Zealand White rabbits.

This result is supported by the study performed to assess the eye irritation potential of the test chemical in rabbits.

Undiluted 50 mg of test chemical was instilled in the conjunctival sac of 2 rabbits for 24 hours.

Slight erythema was observed in the rabbit eyes which disappeared in 24 hours. No corneal damage was observed. Hence, the test chemical can be considered to be not irritating to eyes.

By applying the weight of evidence approach, the test chemical can be considered to be not irritating to eyes. Comparing the annotations with criteria of CLP regulation, the test chemical can be classified under the category "Not Classified".

Justification for classification or non-classification

By applying the weight of evidence approach, the test chemical can be considered to be not irritating to skin and eyes. Comparing the annotations with criteria of CLP regulation, the test chemical can be classified under the category "Not Classified".