Registration Dossier

Administrative data

Description of key information

Skin Irritation:

No cutaneous reactions were observed after 72 hours in the rabbits.

Hence, N-methyl-p-aminophenol sulphate can be considered not irritating to rabbit skin.

Eye Irritation:

Very slight chemosis and redness of the conjunctiva were noted in 1/3 animals 1 hour after ocular instillation only. No other signs of ocular irritation were observed during the study.

Since the effects observed were reversible by 72 hours, n-methyl-p-aminophenol sulphate can be considered 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
Reference:
Composition 0
Composition 0
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Principles of method if other than guideline:
To assess the skin irritation potential of N-methyl-p-aminophenol sulphate in rabbits
GLP compliance:
not specified
Test material information:
Composition 1
Specific details on test material used for the study:
- Name of test material: p-Methylaminophenol sulfate- IUPAC name: Bis(4-hydroxy-N-methylanilinium) sulphate- Molecular formula: C14H20N2O6S- Molecular weight: 344.386 g/mole- Smiles:CNc1ccc(cc1)O.CNc1ccc(cc1)O.OS(=O)(=O)O- Inchl: 1S/2C7H9NO.H2O4S/c2*1-8-6-2-4-7(9)5-3-6;1-5(2,3)4/h2*2-5,8-9H,1H3;(H2,1,2,3,4)- Substance type: Organic- Physical state: Solid crystalline (off white - white- Batch: F1058599- Purity: 99.8%
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
sex: male
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
other: 0.5% aqueous Carboxymethylcellulose
Controls:
yes
Amount / concentration applied:
0.5 ml of 3% N-methyl p-aminophenol sulphate in 0.5% aqueous Carboxymethylcellulose
Duration of treatment / exposure:
4 hours
Observation period:
1, 24, 48 and 72 hours after removal of the dressing
Number of animals:
3 male rabbits
Details on study design:
TEST SITE- Area of exposure: left flank (3 minutes), the anterior right flank (1 hour) and the posterior right flank (4 hours) of one animal- Type of wrap if used: semi-occlusive dressing and a restraining bandage.
Other effects / acceptance of results:
no data available
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
72 h
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
No cutaneous reactions were observed
Interpretation of results:
other: not irritating
Conclusions:
No cutaneous reactions were observed after 72 hours in the rabbits. Hence, N-methyl-p-aminophenol sulphate can be considered not irritating to rabbit skin.
Executive summary:

The dermal irritation potential of N-methyl-p-aminophenol sulphate was assessed in rabbits.The study was performed as per OECD 404 Guidelines. Doses of 0.5 ml of N-methyl-p-aminophenol sulphate at a concentration of 3% were placed on gauze pads and successively applied to a clipped area on the left flank (3 minutes), the anterior right flank (1 hour) and the posterior right flank (4 hours) of one New Zealand White male rabbit. Untreated skin served as a control. Because the dosage form was not irritating in the first animal, it was applied for 4 hours to the two additional animals. The treated sites were observed for signs of irritation at1, 24, 48 and 72 hours after removal of the dressing.

No cutaneous reactions were observed after 72 hours in the rabbits.

Hence,N-methyl-p-aminophenol sulphate can be considered not irritating to 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
Reference:
Composition 0
Composition 0
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Principles of method if other than guideline:
To assess the eye irritation potential of N-methyl-p-aminophenol sulphate in rabbits
GLP compliance:
not specified
Test material information:
Composition 1
Specific details on test material used for the study:
- Name of test material: p-Methylaminophenol sulfate- IUPAC name: Bis(4-hydroxy-N-methylanilinium) sulphate- Molecular formula: C14H20N2O6S- Molecular weight: 344.386 g/mole- Smiles:CNc1ccc(cc1)O.CNc1ccc(cc1)O.OS(=O)(=O)O- Inchl: 1S/2C7H9NO.H2O4S/c2*1-8-6-2-4-7(9)5-3-6;1-5(2,3)4/h2*2-5,8-9H,1H3;(H2,1,2,3,4)- Substance type: Organic- Physical state: Solid crystalline (off white - white)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
sex: male
Vehicle:
other: 0.5% aqueous Carboxymethylcellulose
Controls:
yes
Amount / concentration applied:
0.1 ml of 3% N-methyl p-aminophenol sulphate in 0.5% aqueous Carboxymethylcellulose
Duration of treatment / exposure:
single exposure, The upper and lower lids were held closed for about 1 second to avoid any loss of test substance.
Observation period (in vivo):
1 hour after compound administration, and 24, 48 and 72 hours thereafter.
Duration of post- treatment incubation (in vitro):
no data available
Number of animals or in vitro replicates:
3 male rabbits
Details on study design:
TEST SITE- Area of exposure: conjunctival sac of the left eye of the animals.REMOVAL OF TEST SUBSTANCE- Washing (if done): not washed
Other effects / acceptance of results:
no data available
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
72 h
Reversibility:
fully reversible within: 72 hours
Remarks on result:
probability of weak irritation
Irritant / corrosive response data:
Very slight chemosis and redness of the conjunctiva were noted in 1/3 animals 1 hour after ocular instillation only. No other signs of ocular irritation were observed during the study.
Interpretation of results:
other: not irritating
Conclusions:
Very slight chemosis and redness of the conjunctiva were noted in 1/3 animals 1 hour after ocular instillation only. No other signs of ocular irritation were observed during the study.Since the effects observed were reversible by 72 hours, n-methyl-p-aminophenol sulphate can be considered not irritating to eyes.
Executive summary:

The ocular irritation potential of N-methyl-p-aminophenol sulphate was assessed in rabbits.

The study was performed as per OECD 405 Guidelines. 0.1 ml of 3% N-methyl p-aminophenol sulphate in 0.5% aqueous Carboxymethylcellulose was instilled in the left eye of 3 male New Zealand White rabbits.The upper and lower lids were held closed for about 1 second to avoid any loss of test substance.The untreated right eye of each animal served as a control. The treated eyes remained unwashed throughout the study. The rabbits were observed for signs of irritation1 hour after compound administration, and 24, 48 and 72 hours thereafter.

Very slight chemosis and redness of the conjunctiva were noted in 1/3 animals 1 hour after ocular instillation only. No other signs of ocular irritation were observed during the study.

Since the effects observed were reversible by 72 hours, n-methyl-p-aminophenol sulphate can be considered 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 different studies,p-Methylaminophenol sulfatehas been investigated for potential for dermal irritation to a greater or lesser extent. The studies are based on in vivo experiments in rabbits and guinea pigs.

The dermal irritation potential of N-methyl-p-aminophenol sulphate was assessed (Cosmetic Ingredient Review, 2007) in rabbits. The study was performed as per OECD 404 Guidelines. Doses of 0.5 ml of N-methyl-p-aminophenol sulphate at a concentration of 3% were placed on gauze pads and successively applied to a clipped area on the left flank (3 minutes), the anterior right flank (1 hour) and the posterior right flank (4 hours) of one New Zealand White male rabbit. Untreated skin served as a control. Because the dosage form was not irritating in the first animal, it was applied for 4 hours to the two additional animals. The treated sites were observed for signs of irritation at1, 24, 48 and 72 hours after removal of the dressing.

No cutaneous reactions were observed after 72 hours in the rabbits.

Hence, N-methyl-p-aminophenol sulphate can be considered not irritating to rabbit skin.

 

This result is supported by the experimental study conducted on guinea pigs summarized in OTS0570966, NTRL, dated 082892. Undiluted N-methyl-p-aminophenol sulphate was applied to the depilated abdomen skin of guinea pigs under occlusion. The guinea pigs were observed for signs of irritation from 24 hours of application till 7 days. Slight erythema and edema was observed on the depilated skin after 24 hours. The effects were reversible within 1 week.

Hence, N-methyl-p-aminophenol sulphate can be considered not irritating to guinea pig skin.

The above results are further supported by the experimental study summarized in REPORTS OF THE SCIENTIFIC COMMITTEE ON COSMETOLOGY (NINTH SERIES), Scientific Committee on Cosmetology - SCC; European Commission, 2000. 0.5 ml aqueous solution of 2% sulphate was applied to the intact (left flank) and abraded (right flank) skin of 3 male and 3 female albino Bouscat rabbits under occlusion for 24 hours. The skin readings were scored at 24 or 72 hours.

Slight skin irritation (primary skin irritation index = 0.74/8 at 24 hours exposure and 48 hours after the application ceased) was observed. The Primary Irritation Index was 0.74/8

Hence, N-methyl-p-aminophenol sulphate can be considered not irritating to rabbit skin.

The results of all these studies lead to a conclusion that N-methyl-p-aminophenol sulphate is indeed not irritating to skin.Comparing the above annotations with the criteria of CLP regulation, test chemical can be classified under the category “Not Classified”.

Eye Irritation:

In various studies,p-Methylaminophenol sulfatehas been investigated for potential for ocular irritation to a greater or lesser extent. The studies are based on in vivo experiments in rabbits for the target and its closely related read across substance, 2-Hydroxy-4-methoxybenzophenone [CAS: 131-57-7].

The ocular irritation potential of N-methyl-p-aminophenol sulphate was assessedCosmetic Ingredient Review, 2007)in rabbits. The study was performed as per OECD 405 Guidelines. 0.1 ml of 3% N-methyl p-aminophenol sulphate in 0.5% aqueous Carboxymethylcellulose was instilled in the left eye of 3 male New Zealand White rabbits. The upper and lower lids were held closed for about 1 second to avoid any loss of test substance. The untreated right eye of each animal served as a control. The treated eyes remained unwashed throughout the study. The rabbits were observed for signs of irritation1 hour after compound administration, and 24, 48 and 72 hours thereafter.

Very slight chemosis and redness of the conjunctiva were noted in 1/3 animals 1 hour after ocular instillation only. No other signs of ocular irritation were observed during the study.

Since the effects observed were reversible by 72 hours, n-methyl-p-aminophenol sulphate can be considered not irritating to eyes.

This result is supported by the experimental study summarized in OF THE SCIENTIFIC COMMITTEE ON COSMETOLOGY (NINTH SERIES), Scientific Committee on Cosmetology - SCC; European Commission, 2000. 0.1 ml 2% aqueous solution of p-methylaminophenol sulfate was instilled in the conjunctival sac of 6 male albino rabbits. The treated eyes remained unwashed throughout the study. The reactions were read and scored at1 day, 2, 3, 4 and 7 days after treatment. No signs of irritation were observed when 2% aqueous solution of p-methylaminophenol sulfate was exposed to eyes of rabbits.

Hence, p-methylaminophenol sulfate can be considered not irritating to eyes.

The above studies are supported by the experimental study summarized in JOURNAL OF THE AMERICAN COLLEGE OF TOXICOLOGY, Volume 2, Number 5, 1983; for the closely related read across substance, 2-Hydroxy-4-methoxybenzophenone [CAS: 131-57-7]. The study was performed as per Draize method. 100 mg of the undiluted test chemical was instilled in to the eyes of 6 rabbits. The eyes remained unwashed throughout the test. The rabbits were observed for signs of irritation and scored at 1,2,3,4 and 7 days.

The average scores per day till 7 days of observation were 0.0. Hence, 2-Hydroxy-4-methoxybenzophenone can be considered to be not irritating to rabbit eyes.

Based on the available data for the target and its closely related read across substance,p-Methylaminophenol sulfate was considered not irritating to eyes.Comparing the above annotations with the criteria of CLP regulation, test chemical can be classified under the category “Not Classified

Justification for classification or non-classification

Available studies for p-Methylaminophenol sulfate indicate that it is not likely to cause irritation to skin and eyes.

Hence, p-Methylaminophenol sulfate can be considered as “Not Irritating” to skin and eyes and can be classified under the category “Not Classified” as per CLP regulation.