Registration Dossier

Administrative data

Description of key information

Skin irritation:

The dermal irritation potential of4-hydroxy-7-[(5-hydroxy-7-sulfonaphthalen-2-yl)amino]naphthalene-2-sulfonic acid (CAS No: 87-03-6) was estimated using OECD QSAR toolbox version 3.4 with logPow as the primary descriptor. The substance 4-hydroxy-7-[(5-hydroxy-7-sulfonaphthalen-2-yl)amino]naphthalene-2-sulfonic acid (CAS No: 87-03-6) was estimated to be not irritating to the skin of New Zealand White rabbits. Based on the estimated result 4-hydroxy-7-[(5-hydroxy-7-sulfonaphthalen-2-yl)amino]naphthalene-2-sulfonic acid (CAS No: 87-03-6) can be considered to be not irritating to skin and can be classified under the category ˋ Not Classified’ as per CLP regulation.

Eye irritation:

The ocular irritation potential of 4-hydroxy-7-[(5-hydroxy-7-sulfonaphthalen-2-yl)amino]naphthalene-2-sulfonic acid (CAS No: 87-03-6) was estimated using OECD QSAR toolbox version 3.4 with logPow as the primary descriptor. The substance 4-hydroxy-7-[(5-hydroxy-7-sulfonaphthalen-2-yl)amino]naphthalene-2-sulfonic acid (CAS No: 87-03-6) was estimated to be not irritating into the eyes of New Zealand White rabbits. Based on the estimated result 4-hydroxy-7-[(5-hydroxy-7-sulfonaphthalen-2-yl)amino]naphthalene-2-sulfonic acid (CAS No: 87-03-6) can be considered to be not irritating to eye and can be classified under the category ˋ Not Classified’ as per CLP regulation.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
(Q)SAR
Adequacy of study:
other information
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification
Justification for type of information:
Data is from OECD QSAR toolbox version 3.4 and QMRF report has been attachedData is from OECD QSAR toolbox version 3.4 and QMRF report has been attached
Qualifier:
according to
Guideline:
other: estimated data
Principles of method if other than guideline:
Prediction is done using QSAR Toolbox version 3.4
GLP compliance:
not specified
Specific details on test material used for the study:
- Name of test material: 4-hydroxy-7-[(5-hydroxy-7-sulfonaphthalen-2-yl)amino]naphthalene-2-sulfonic acid
- Molecular formula: C20H15NO8S2
- Molecular weight: 461.47 g/mol
- Smiles notation: O=S(=O)(O)c1cc(O)c2c(cc(Nc3ccc4c(cc(S(=O)(=O)O)cc4O)c3)cc2)c1
- InChl: 1S/C20H15NO8S2/c22-19-9-15(30(24,25)26)7-11-5-13(1-3-17(11)19)21-14-2-4-18-12(6-14)8-16(10-20(18)23)31(27,28)29/h1-10,21-23H,(H,24,25,26)(H,27,28,29)
- Substance type: Organic
- Physical state: Solid
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
No data available
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
not specified
Controls:
not specified
Amount / concentration applied:
No data available
Duration of treatment / exposure:
4 hours
Observation period:
72 hours
Number of animals:
3
Details on study design:
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 skin irritation was observed.

Estimation method: Takes mode value from the 5 nearest neighbours
Domain  logical expression:Result: In Domain

((((((((((((("a" or "b" or "c" or "d" )  and ("e" and ( not "f") )  )  and ("g" and ( not "h") )  )  and ("i" and ( not "j") )  )  and ("k" and ( not "l") )  )  and ("m" and ( not "n") )  )  and ("o" and ( not "p") )  )  and ("q" and ( not "r") )  )  and ("s" and ( not "t") )  )  and "u" )  and ("v" and ( not "w") )  )  and ("x" and ( not "y") )  )  and ("z" and "aa" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Very strong binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as AN2 AND AN2 >> Michael-type addition to quinoid structures  AND AN2 >> Michael-type addition to quinoid structures  >> N-Substituted Aromatic Amines AND AN2 >> Michael-type addition to quinoid structures  >> Substituted Phenols by Protein binding by OASIS v1.4

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Class 2 (less inert compounds) by Acute aquatic toxicity classification by Verhaar (Modified)

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Acid moiety AND Phenols, Poly by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Very strong binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Non binder, MW>500 by Estrogen Receptor Binding

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Very strong binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Weak binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Very strong binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Weak binder, NH2 group by Estrogen Receptor Binding

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Very strong binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Strong binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Very strong binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Non binder, non cyclic structure by Estrogen Receptor Binding

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Very strong binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Non binder, impaired OH or NH2 group by Estrogen Receptor Binding

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Very strong binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as Strong binder, NH2 group by Estrogen Receptor Binding

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as Phenols by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as Activated N-heterocycles OR Aromatic amines OR Inclusion rules not met OR Ketones by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "u"

Referential boundary: The target chemical should be classified as Bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "v"

Referential boundary: The target chemical should be classified as Aromatic amine AND Aryl AND Fused carbocyclic aromatic AND Naphtalene AND Phenol AND Sulfonic acid by Organic Functional groups

Domain logical expression index: "w"

Referential boundary: The target chemical should be classified as Alkane, branched with tertiary carbon OR Alkoxy by Organic Functional groups

Domain logical expression index: "x"

Referential boundary: The target chemical should be classified as Aromatic amine AND Aryl AND Fused carbocyclic aromatic AND Naphtalene AND Phenol AND Sulfonic acid by Organic Functional groups

Domain logical expression index: "y"

Referential boundary: The target chemical should be classified as Biphenyl by Organic Functional groups

Domain logical expression index: "z"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.0575

Domain logical expression index: "aa"

Parametric boundary:The target chemical should have a value of log Kow which is <= 2.52

Interpretation of results:
other: not irritating
Conclusions:
The substance 4-hydroxy-7-[(5-hydroxy-7-sulfonaphthalen-2-yl)amino]naphthalene-2-sulfonic acid (CAS No: 87-03-6) was estimated to be not irritating to the skin of New Zealand White rabbits. Based on the estimated result 4-hydroxy-7-[(5-hydroxy-7-sulfonaphthalen-2-yl)amino]naphthalene-2-sulfonic acid (CAS No: 87-03-6) can be considered to be not irritating to skin.
Executive summary:

The dermal irritation potential of4-hydroxy-7-[(5-hydroxy-7-sulfonaphthalen-2-yl)amino]naphthalene-2-sulfonic acid (CAS No: 87-03-6) was estimated using OECD QSAR toolbox version 3.4 with logPow as the primary descriptor. The substance 4-hydroxy-7-[(5-hydroxy-7-sulfonaphthalen-2-yl)amino]naphthalene-2-sulfonic acid (CAS No: 87-03-6) was estimated to be not irritating to the skin of New Zealand White rabbits. Based on the estimated result 4-hydroxy-7-[(5-hydroxy-7-sulfonaphthalen-2-yl)amino]naphthalene-2-sulfonic acid (CAS No: 87-03-6) can be considered to be not irritating to skin and can be classified under the category ˋ Not Classified’ as per CLP regulation.

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:
(Q)SAR
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification
Justification for type of information:
Data is from OECD QSAR toolbox version 3.4 and QMRF report has been attached
Qualifier:
according to
Guideline:
other: Estimated data
Principles of method if other than guideline:
Prediction is done using QSAR Toolbox version 3.4
GLP compliance:
not specified
Specific details on test material used for the study:
- Name of test material: 4-hydroxy-7-[(5-hydroxy-7-sulfonaphthalen-2-yl)amino]naphthalene-2-sulfonic acid
- Molecular formula: C20H15NO8S2
- Molecular weight: 461.47 g/mol
- Smiles notation: O=S(=O)(O)c1cc(O)c2c(cc(Nc3ccc4c(cc(S(=O)(=O)O)cc4O)c3)cc2)c1
- InChl: 1S/C20H15NO8S2/c22-19-9-15(30(24,25)26)7-11-5-13(1-3-17(11)19)21-14-2-4-18-12(6-14)8-16(10-20(18)23)31(27,28)29/h1-10,21-23H,(H,24,25,26)(H,27,28,29)
- Substance type: Organic
- Physical state: Solid
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
No data available
Vehicle:
not specified
Controls:
not specified
Amount / concentration applied:
No data available
Duration of treatment / exposure:
72 hours
Observation period (in vivo):
72 hours
Duration of post- treatment incubation (in vitro):
No data available
Number of animals or in vitro replicates:
3
Details on study design:
No data available
Irritation parameter:
overall irritation score
Basis:
mean
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
No eye irritation was observed.

Estimation method: Takes mode value from the 5 nearest neighbours
Domain  logical expression:Result: In Domain

(((((((((("a" or "b" or "c" or "d" )  and ("e" and ( not "f") )  )  and ("g" and ( not "h") )  )  and ("i" and ( not "j") )  )  and ("k" and ( not "l") )  )  and "m" )  and ("n" and ( not "o") )  )  and ("p" and ( not "q") )  )  and ("r" and ( not "s") )  )  and ("t" and "u" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Very strong binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as AN2 AND AN2 >> Michael-type addition to quinoid structures  AND AN2 >> Michael-type addition to quinoid structures  >> N-Substituted Aromatic Amines AND AN2 >> Michael-type addition to quinoid structures  >> Substituted Phenols by Protein binding by OASIS v1.4

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Class 2 (less inert compounds) by Acute aquatic toxicity classification by Verhaar (Modified)

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Acid moiety AND Phenols, Poly by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as No alert found by in vivo mutagenicity (Micronucleus) alerts by ISS

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as 1,3-dialkoxy-benzene OR 1-phenoxy-benzene OR Aliphatic halogen OR alpha,beta-unsaturated carbonyls OR Aromatic diazo OR Aromatic mono- and dialkylamine OR Aromatic N-acyl amine OR Epoxides and aziridines OR H-acceptor-path3-H-acceptor OR Nitro-aromatic OR Primary aromatic amine, hydroxyl amine and its derived esters OR Simple aldehyde by in vivo mutagenicity (Micronucleus) alerts by ISS

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Aromatic Amine Type Compounds AND Phenol Type Compounds by Oncologic Primary Classification

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Halogenated Aromatic Hydrocarbon Type Compounds OR Not classified by Oncologic Primary Classification

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as No alert found by Protein binding alerts for Chromosomal aberration by OASIS v.1.2

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Acylation involving an activated (glucuronidated) ester group OR Acylation >> Acylation involving an activated (glucuronidated) ester group >> Arenecarboxylic Acid Esters OR AN2 OR AN2 >> Michael addition to the quinoid type structures OR AN2 >> Michael addition to the quinoid type structures >> Hydroxylated Phenols OR AN2 >> Michael addition to the quinoid type structures >> Substituted Phenols by Protein binding alerts for Chromosomal aberration by OASIS v.1.2

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Non-Metals by Groups of elements

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Halogens by Groups of elements

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Not categorized by Repeated dose (HESS)

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as p-Alkylphenols (Hepatotoxicity) Rank A by Repeated dose (HESS)

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Not categorized by Repeated dose (HESS)

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Methyldopa (Hepatotoxicity) Alert by Repeated dose (HESS)

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as Phenols by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as Aromatic amines by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "t"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.0488

Domain logical expression index: "u"

Parametric boundary:The target chemical should have a value of log Kow which is <= 1.28

Interpretation of results:
other: not irritating
Conclusions:
he substance 4-hydroxy-7-[(5-hydroxy-7-sulfonaphthalen-2-yl)amino]naphthalene-2-sulfonic acid (CAS No: 87-03-6) was estimated to be not irritating into the eyes of New Zealand White rabbits. Based on the estimated result 4-hydroxy-7-[(5-hydroxy-7-sulfonaphthalen-2-yl)amino]naphthalene-2-sulfonic acid (CAS No: 87-03-6) can be considered to be not irritating to eye.
Executive summary:

The ocular irritation potential of4-hydroxy-7-[(5-hydroxy-7-sulfonaphthalen-2-yl)amino]naphthalene-2-sulfonic acid (CAS No: 87-03-6) was estimated using OECD QSAR toolbox version 3.4 with logPow as the primary descriptor. The substance 4-hydroxy-7-[(5-hydroxy-7-sulfonaphthalen-2-yl)amino]naphthalene-2-sulfonic acid (CAS No: 87-03-6) was estimated to be not irritating into the eyes of New Zealand White rabbits. Based on the estimated result 4-hydroxy-7-[(5-hydroxy-7-sulfonaphthalen-2-yl)amino]naphthalene-2-sulfonic acid (CAS No: 87-03-6) can be considered to be not irritating to eye and can be classified under the category ˋ Not Classified’ as per CLP regulation.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation:

Various studieshas been investigated for the test chemical4-hydroxy-7-[(5-hydroxy-7-sulfonaphthalen-2-yl)amino]naphthalene-2-sulfonic acid (CAS No: 87-03-6)to observe the potential for dermal irritation to a greater or lesser extent. The studies are based on in vivo experiments in rabbits for target chemical4-hydroxy-7-[(5-hydroxy-7-sulfonaphthalen-2-yl)amino]naphthalene-2-sulfonic acid (CAS No: 87-03-6) and its structurally similar read across substancesResorcinol (CAS No: 108-46-3)and 4,4'-sulphonyldiphenol (CAS No: 80-09-1) .The predicted data using the OECD QSAR toolbox has also been compared with the experimental data and summarized as below;

 

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the skin irritation potential was estimated for test chemical4-hydroxy-7-[(5-hydroxy-7-sulfonaphthalen-2-yl)amino]naphthalene-2-sulfonic acid (CAS No: 87-03-6) .The chemical 4-hydroxy-7-[(5-hydroxy-7-sulfonaphthalen-2-yl)amino]naphthalene-2-sulfonic acid (CAS No: 87-03-6) is estimated to be not irritating to skin of New Zealand White rabbits.

 

The G. K. LLOYO et.al. ( Food and Cosmetics Toxicology Vol. 15, pp. 607-610. Pergamon Press ,1977) conducted skin irritation study for read across substance Resorcinol (CAS No: 108-46-3) on intact and abraded skin of three New Zealand White rabbits according to the United States Code of Federal Regulations (Federal Hazardous Substances Act Regulations 16: Section 1500.41, Method of testing primary irritant substances).The test involved the dermal application of a 2.5% (w/v) solution of resorcinol to intact or abraded skin and the dermal reactions were evaluated over period of 72 hours. The chemical caused no dermal effects with primary irritation index of 0.0.Thereforethe chemical Resorcinol (CAS No: 108-46-3) wasconsidered to be not irritating torabbits’ skin.

 

 

Another dermal irritation study was reported for the same read across substance Resorcinol (CAS No: 108-46-3) by United Nations Environmental Programme (UNEP) {(Resorcinol - SIDS Dossier ; OECD HPV Chemicals Programme, SIDS Dossier, approved at SIAM 27 (14-16 October 2008)} on rabbits in accordance with OECD Guideline404 "Acute Dermal Irritation/Corrosion" and EC Directive No 92/69/EEC.B.4In this test,Resorcinol was used at the concentration of 2.5%. The dosage was first evaluated in a single animal. The duration of exposure was 3 minutes in the anterior left flank, 1 hour in the anterior right flank, and four hours on the posterior right flank. Since the dosage was not an irritant on this first animal, it was applied for 4 hours to two other animals. Doses of 0.5 mL of the dosage from preparations were placed on a dry gauze pad which was then applied to the anterior and posterior right flanks (application for 1 and 4 hours, respectively) on the left flank (application 3 minutes) of the animals. The gauze pad was held in contact with the skin by means of a hypoallergenic adhesive aerated semi-occlusive dressing and a restraining bandage. Untreated skin served as the control. No residual test substance was observed on removal of the dressing. Evaluation at 1, 24, 48 and 72 hours post treatment. No cutaneous reactions were observed during the study. Thus the study was ended on day 4 in the absence of persistent irritation reactions.Hencethe chemical Resorcinol (CAS No: 108-46-3) was considered to be not irritating to rabbits’ skin.

The above results were further supported by the skin irritation study carried out by OECD SIDS {SIDS Dossier OECD HPV Chemical Programme, SIDS Dossier, approved at CoCAM 4 (16/04/2013)} for read across substance 4,4'-sulphonyldiphenol (CAS No: 80-09-1) in New Zealand White rabbits in accordance with OECD Guideline 404 (Acute Dermal Irritation / Corrosion) under occlusive condition.In this test, 24 hours before treatment the back of the experimental animal was shaven of at least 6 cm2, by means of an electric clipper. A gauze patch bearing 500mg (0.5 g) of4,4'-sulphonyldiphenolwas applied to the skin and loosely held in place by adhesive but non irritating tape. The substance was water moistened before application. After removal of the dressings the skin reaction was assessed on the basis of an evaluation scheme, after 1, 24, 48, 72 hours and during the following observation period. The score obtained is defined as the "index of primary cutaneous irritation". The animals showed normal body weight development.The treated rabbits were free of findings at the 1 hour scoring thus the test was finished after 3 observation days. Therefore the chemical4,4'-sulphonyldiphenol (CAS No: 80-09-1) wasconsidered to be not irritating toskin of New Zealand White rabbits.

 

Thus on the basis of available data for thetarget chemical4-hydroxy-7-[(5-hydroxy-7-sulfonaphthalen-2-yl)amino]naphthalene-2-sulfonic acid (CAS No: 87-03-6) and its structurally similar read across substancesResorcinol (CAS No: 108-46-3)and 4,4'-sulphonyldiphenol (CAS No: 80-09-1),it can be concluded thatchemical 4-hydroxy-7-[(5-hydroxy-7-sulfonaphthalen-2-yl)amino]naphthalene-2-sulfonic acid (CAS No: 87-03-6) is unable to cause skin irritation and 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:

In different studies,the test chemical4-hydroxy-7-[(5-hydroxy-7-sulfonaphthalen-2-yl)amino]naphthalene-2-sulfonic acid (CAS No: 87-03-6) has been investigated for potential for ocular irritationto a greater or lesser extent. The studies are based on in vivo experiments in rabbits for target chemical4-hydroxy-7-[(5-hydroxy-7-sulfonaphthalen-2-yl)amino]naphthalene-2-sulfonic acid (CAS No: 87-03-6)its structurally similar read across substancesResorcinol (CAS No: 108-46-3)and 4,4'-sulphonyldiphenol (CAS No: 80-09-1).The predicted data using the OECD QSAR toolbox has also been compared with the experimental data and summarized as below;

 

 

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the eye irritation potential was estimated for test chemical4-hydroxy-7-[(5-hydroxy-7-sulfonaphthalen-2-yl)amino]naphthalene-2-sulfonic acid (CAS No: 87-03-6) .The chemical 4-hydroxy-7-[(5-hydroxy-7-sulfonaphthalen-2-yl)amino]naphthalene-2-sulfonic acid (CAS No: 87-03-6) is estimated to be not irritating to eye of New Zealand White rabbits.

 

The G. K. LLOYO et.al. ( Food and Cosmetics Toxicology Vol. 15, pp. 607-610. Pergamon Press ,1977) conducted an eye irritation study for read across substance Resorcinol (CAS No: 108-46-3) on three New Zealand White rabbits according to the United States Code of Federal Regulations (Federal Hazardous Substances Act Regulations 16: Section 1500.42, Test for eye irritants).The installation of 2.5% (w/v) solution of resorcinol into the eyes (rinsing 10 s after application) produced only mild conjunctival inflammation which was disappeared within 24 h post-application. Since the ocular lesions were not persisted, the chemical Resorcinol (CAS No: 108-46-3) wasconsidered to be not irritating to eyes of three New Zealand White rabbits.

 

Another ocular irritation study was reported for the same read across substance Resorcinol (CAS No: 108-46-3) by United Nations Environmental Programme (UNEP) {(Resorcinol - SIDS Dossier ; OECD HPV Chemicals Programme, SIDS Dossier, approved at SIAM 27 (14-16 October 2008)} on rabbits in accordance with OECD Guideline 405 (Acute Eye Irritation / Corrosion)and EC Directive 92/69/EEC B.5.In this test,Resorcinol was used at the concentration of 2.5% and placed into the conjunctival sac of the left eye of each animal, after gently pulling away the lower lid from the eyeball. The lids were then held together for about one second in order to prevent loss of the test material. The right eye remained untreated and served as a control.The ocular reactions were examined 1, 24, 48 and 72 hours after substance instillation anddaily for evaluating conjunctival reactions, iritis and corneal opacification. Mean scores calculated for each animal over 24, 48 and 72 hours were 0.0, 0.0, and 0.0 for chemosis, iris lesions and corneal opacity, respectively. In the case of redness of the conjunctiva, scores were 0.0, 0.0 and 0.3, respectively. Except for the very slight redness of the conjunctiva (grade 1) noted in 2/3 animals on day 1 or 2, no ocular reactions were observed during the study. Hencethe chemical Resorcinol (CAS No: 108-46-3) was considered to be not irritating to rabbits’ eye.

 

The above results were further supported by the eye irritation study carried out by OECD SIDS {SIDS Dossier OECD HPV Chemical Programme, SIDS Dossier, approved at CoCAM 4 (16/04/2013)} for read across substance 4,4'-sulphonyldiphenol (CAS No: 80-09-1) in New Zealand White rabbits in accordance with OECD Guideline 405 (Acute Eye Irritation / Corrosion).In this test, 0.1 g of 4,4`-sulphonyldipenol was placed into the conjunctival sac of the right eye of each animal, after gently pulling away the lower lid from the eyeball. The lids were then held together for about one second in order to prevent loss of the test material. The left eye remained untreated and served as a control.The ocular reactions were examined 1, 24, 48 and 72 hours after substance instillation and again during the following observation period by means of a slit-lamp.Slight lesions were observed but did not persist upto 7 days.Since the animals had recovered at the end of the observation period of 7 days,the chemical4,4'-sulphonyldiphenol (CAS No: 80-09-1) wasconsidered to be not irritating toeyes of New Zealand White rabbits.

 

Thus on the basis of available data for thetarget chemical4-hydroxy-7-[(5-hydroxy-7-sulfonaphthalen-2-yl)amino]naphthalene-2-sulfonic acid (CAS No: 87-03-6) and its structurally similar read across substancesResorcinol (CAS No: 108-46-3)and 4,4'-sulphonyldiphenol (CAS No: 80-09-1),it can be concluded thatchemical 4-hydroxy-7-[(5-hydroxy-7-sulfonaphthalen-2-yl)amino]naphthalene-2-sulfonic acid (CAS No: 87-03-6) is unable to cause eye irritation and considered as not irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

 

 

Justification for classification or non-classification

The skin and eye irritation potential of test chemical 4-hydroxy-7-[(5-hydroxy-7-sulfonaphthalen-2-yl)amino]naphthalene-2-sulfonic acid (CAS No: 87-03-6) and its structurally similar read across substanceswere observed in various studies. The results obtained from these studies indicate that the chemical 4-hydroxy-7-[(5-hydroxy-7-sulfonaphthalen-2-yl)amino]naphthalene-2-sulfonic acid is unlikely to cause skin and eye irritation. Hence 4-hydroxy-7-[(5-hydroxy-7-sulfonaphthalen-2-yl)amino]naphthalene-2-sulfonic acid (CAS No: 87-03-6) can be classified under the category “Not Classified” for skin and eye as per CLP.