Registration Dossier

Administrative data

Description of key information

Skin Irritation

None of the rabbits treated with the test chemical showed any signs of irritation during the 72 hours observation period. The Primary Irritation Index was 0.0.

Based on the scores and observations, the test chemical was considered to be not irritating to albino New Zealand White rabbit skin.

Eye Irritation

Treatment with the test chemical gave rise to a yellow coloration of the cornea 1 hr after instillation, but the cornea was clear by the 24-hr reading, and there was no observable irritant response in any of the animals in this group.

According to the Code of Federal Regulations, Test for Eye Irritants, the test chemical was scored as ± .

Based on the scores and observations, the test chemical can be considered to be not irritating to eyes.

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: Consumer Product Safety Commission of the USA (Code of Federal Regulations, Title 16, Sec. 1500.41)
Principles of method if other than guideline:
To assess the dermal irritancy potential of the test chemical in rabbits
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
The albino rabbits used for the assessment.
Type of coverage:
other: intact and abraded skin
Preparation of test site:
other: intact and abraded
Vehicle:
other: Suspension in 0.5% aqueous gum tragacanth, containing 0.05% Na2SO3.
Controls:
not specified
Amount / concentration applied:
2.5% (w/v) Suspension in 0.5% aqueous gum tragacanth, containing 0.05% Na2SO3.
Duration of treatment / exposure:
Single exposure
Observation period:
72 hrs
Number of animals:
3
Details on study design:
SCORING SYSTEM: Based on the definition of skin irritation given in the (Code of Federal Regulations, Title 16, Sec. 1500.41).
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
72 h
Score:
0
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
None of the animals treated showed any response to treatment

Table: Results of the skin and eye irritancy studies on rabbits

Compound

Skin Irritation

(Primary Irritation Index)

Eye Irritation **

99 -57 -0

0

±

**Categorized as + or - according to whether extrapolation of the result would be expected to give a positive or negative in the Code of Federal Regulations, Test for Eye Irritants (Title 16, Sec. 1500.42).

Interpretation of results:
other: not irritating
Conclusions:
None of the rabbits treated with the test chemical showed any signs of irritation during the 72 hours observation period. The Primary Irritation Index was 0.0.
Based on the scores and observations, the test chemical was considered to be not irritating to albino New Zealand White rabbit skin.
Executive summary:

The dermal irritancy potential of the test chemical was evaluated in rabbits. The study was conducted as per Consumer Product Safety Commission of the USA (Code of Federal Regulations, Title 16, Sec. 1500.41).2.5% (w/v) Suspension of the test chemical in 0.5% aqueous gum tragacanth, containing 0.05% Na2SO3was applied to the intact and abraded skin of 3 New Zealand White albino rabbits. The rabbits were observed for signs of irritation till 72 hours and the reactions were scored based on the definition of skin irritation given in the Code of Federal Regulations, Title 16, Sec.1500.41.

None of the rabbits treated with the test chemical showed any signs of irritation during the 72 hours observation period. The Primary Irritation Index was 0.0.

Based on the scores and observations, the test chemical was considered to be not irritating to albino New Zealand White rabbit skin.

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:
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: Code of Federal Regulations, Test for Eye Irritants (Title 16, Sec. 1500.42).
Principles of method if other than guideline:
To assess the ocular irritancy potential of the test chemical in rabbits
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Vehicle:
other: Suspension in 0.5% aqueous gum tragacanth, containing 0.05% Na2SO3.
Controls:
yes, concurrent no treatment
Amount / concentration applied:
2.5%(w/v) Suspension in 0.5% aqueous gum tragacanth, containing 0.05% Na2SO3.
Duration of treatment / exposure:
single exposure
Observation period (in vivo):
1, 24 hours
Duration of post- treatment incubation (in vitro):
no data available
Number of animals or in vitro replicates:
3
Details on study design:
SCORING SYSTEM: Categorized as + or - according to whether extrapolation of the result would be expected to give a positive or negative test for eye irritation based on the definition in the Code of Federal Regulations, Test for Eye Irritants (Title 16, Sec. 1500.42).

REMOVAL OF TEST SUBSTANCE
Washing (if done): 50 ml of lukewarm water (37°C)
Time after start of exposure: 10 seconds after instillation
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 1 hours
Reversibility:
fully reversible within: 24 hours
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
Treatment with the test chemical gave rise to a yellow coloration of the cornea 1 hr after instillation, but the cornea was clear by the 24-hr reading, and there was no observable irritant response in any of the animals in this group.
According to the Code of Federal Regulations, Test for Eye Irritants, the test chemical was scored as ± ,.

Table: Results of the skin and eye irritancy studies on rabbits

Compound

Skin Irritation

(Primary Irritation Index)

Eye Irritation **

99 -57 -0

0

±

**Categorized as + or - according to whether extrapolation of the result would be expected to give a positive or negative in the Code of Federal Regulations, Test for Eye Irritants (Title 16, Sec. 1500.42).

                                                  

Interpretation of results:
other: not irritating
Conclusions:
The irritant effects on rabbit eye mucosa, was assessed for the test chemical.Treatment with the test chemical gave rise to a yellow coloration of the cornea 1 hr after instillation, but the cornea was clear by the 24-hr reading, and there was no observable irritant response in any of the animals in this group.
According to the Code of Federal Regulations, Test for Eye Irritants, the test chemical was scored as ± .
Based on the scores and observations, the test chemical can be considered to be not irritating to eyes.
Executive summary:

The irritant effects on rabbit eye mucosa, was assessed for the test chemical.

 

The procedure for the eye tests was also based on that prescribed in the Code of Federal Regulations (Title 16, Sec. 1500.42).The test chemical was prepared as a 2.5% (w/v) solution or suspension. (Suspension in 0.5% aqueous gum tragacanth, containing 0.05% Na2SO3). Eleven groups of three rabbits were used to test solutions, each of which was instilled into one eye of each of three rabbits. The eyes of all the rabbits were irrigated with 50 ml of lukewarm (37°C) water, 10 sec after instillation of the test material.

Treatment with the test chemical gave rise to a yellow coloration of the cornea 1 hr after instillation, but the cornea was clear by the 24-hr reading, and there was no observable irritant response in any of the animals in this group.

According to the Code of Federal Regulations, Test for Eye Irritants, the test chemical was scored as ± .

Based on the scores and observations, the test chemical can be considered to be not irritating to eyes.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin Irritation

In various studies, the test chemical been investigated for potential to cause dermal irritation to a greater or lesser extent. The studies are based on in vivo experiments in rabbits for the test chemicals. The results are summarized as follows:

The dermal irritancy potential of the test chemical was evaluated in rabbits. The study was conducted as per Consumer Product Safety Commission of the USA (Code of Federal Regulations, Title 16, Sec. 1500.41).2.5% (w/v) Suspension of 2-amino-4-nitrophenol in 0.5% aqueous gum tragacanth, containing 0.05% Na2SO3was applied to the intact and abraded skin of 3 New Zealand White albino rabbits. The rabbits were observed for signs of irritation till 72 hours and the reactions were scored based on the definition of skin irritation given in the  Code of Federal Regulations, Title 16, Sec.1500.41.

None of the rabbits treated with the test chemical showed any signs of irritation during the 72 hours observation period. The Primary Irritation Index was 0.0.

Based on the scores and observations, the test chemical was considered to be not irritating to albino New Zealand White rabbit skin.

This is supported by the results of a similar study performed as per Consumer Product Safety Commission of the USA (Code of Federal Regulations, Title 16, Sec. 1500.41) to evaluate the irritation potential of the test chemical.2.5% (w/v) Suspension of the test chemical in 0.5% aqueous gum tragacanth, containing 0.05% Na2SO3was applied to the intact and abraded skin of 3 New Zealand White albino rabbits. The rabbits were observed for signs of irritation till 72 hours and the reactions were scored based on the definition of skin irritation given in the  (Code of Federal Regulations, Title 16, Sec.1500.41).

None of the rabbits treated with the test chemical showed any signs of irritation during the 72 hours observation period. The Primary Irritation Index was 0.0.

Based on the scores and observations, the test chemical was considered to be not irritating to albino New Zealand White rabbit skin.

The above results are further supported by a similar study performed as per Consumer Product Safety Commission of the USA (Code of Federal Regulations, Title 16, Sec. 1500.41) to determine the irritation potential of the test chemical.2.5% (w/v) Suspension of the test chemical in 0.5% aqueous gum tragacanth, containing 0.05% Na2SO3was applied to the intact and abraded skin of 3 New Zealand White albino rabbits. The rabbits were observed for signs of irritation till 72 hours and the reactions were scored based on the definition of skin irritation given in the Code of Federal Regulations, Title 16, Sec.1500.41.

None of the rabbits treated with the test chemical showed any signs of irritation during the 72 hours observation period. The Primary Irritation Index was 0.0.

Based on the scores and observations, the test chemical was considered to be not irritating to albino New Zealand White rabbit skin.

Considering the results of the in vivo studies, the test chemical 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

Various studies have been summarized to determine the extent of ocular damage caused by the test chemical in living organisms. These results include in vivo experimental studies on rabbits for the test chemicals.

The irritant effects on rabbit eye mucosa, was assessed for the test chemical.

The procedure for the eye tests was also based on that prescribed in the Code of Federal Regulations (Title 16, Sec. 1500.42).The test chemical was prepared as a 2.5% (w/v) solution or suspension. (Suspension in 0.5% aqueous gum tragacanth, containing 0.05% Na2SO3). Eleven groups of three rabbits were used to test solutions, each of which was instilled into one eye of each of three rabbits. The eyes of all the rabbits were irrigated with 50 ml of lukewarm (37°C) water, 10 sec after instillation of the test material. Treatment with the test chemical gave rise to a yellow coloration of the cornea 1 hr after instillation, but the cornea was clear by the 24-hr reading, and there was no observable irritant response in any of the animals in this group.

According to the Code of Federal Regulations, Test for Eye Irritants, the test chemical was scored as ± .

Based on the scores and observations, the test chemical can be considered to be not irritating to eyes.

This is supported by the results of a Standard Draize test performed to evaluate the irritation potential of the test chemical. 100 mg of the test chemical was instilled into the eyes and observed for effects till 24 hours. Moderate irritation effects were observed after 24 hours of observation [No other details mentioned].

Based on these observations, the test chemical was considered to be moderately irritating to eyes.

In another study conducted according the procedure based on that prescribed in the Code of Federal Regulations (Title 16, Sec. 1500.42), the irritation potential of the test chemical was assessed in rabbits. The test chemical was prepared as a 2.5% (w/v) solution or suspension. (Suspension in 0.5% aqueous gum tragacanth, containing 0.05% Na2SO3). Eleven groups of three rabbits were used to test solutions, each of which was instilled into one eye of each of three rabbits. The eyes of all the rabbits were irrigated with 50 ml of lukewarm (37°C) water, 10 sec after instillation of the test material.

None of the three animals treated with the test material showed any response to treatment, and although occasional transient mild conjunctival inflammation was observed. The reactions did not persist for more than 24 hr.

Thus, the substance was considered to be non irritating to eyes.

The above results are supported by a similar study performed according to assess the ocular irritancy potential of the test chemical in rabbits.2.5% (w/v) Suspension of the test chemical in 0.5% aqueous gum tragacanth, (containing 0.05% Na2SO3 pH adjusted to 7) was instilled into the eyes of 3 rabbits. The treated eyes were rinsed with 50 ml of lukewarm water (37°C) 10 seconds after instillation of the test chemical. The eyes were observed for signs of irritation till 24 hours.

Occasional, transient mild conjunctival inflammation was observed in the rabbit eyes that did not persist for more than 24 hours.

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

Even though results of one study claim that the test chemical can cause moderate irritation to rabbit eyes, but the study fails to mention regarding the reversibility of the effects. These details are fulfilled in the key study where the corneal effects got cleared by the end of 24 hours and no other significant signs of ocular irritation were noted. Taking all this into consideration, the test chemical 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”.

Justification for classification or non-classification

Available studies for the test chemical indicate that the test chemical lacks the potential to cause any irritation to eyes and skin. Hence, the test chemical can be considered to be not irritating to eyes and skin. It can further be classified under the category "Not Classified” as per CLP regulation.