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Description of key information

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:
key study
Reliability:
2 (reliable with restrictions)
Justification for type of information:
QSAR prediction: migrated from IUCLID 5.6
Qualifier:
according to guideline
Guideline:
other: As menioned below
Principles of method if other than guideline:
Prediction is done using QSAR Toolbox version 3.3
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
- Source: Bred on the premises of the testing laboratory
- Age at study initiation: 3 to 4 months
- Weight at study initiation: Males: 2.33 kg; Females: 2.06 kg
- Housing: Caged singly
- Diet: A commercial irradiated diet (Styles-Oxoid), ad libitum
- Water: Sterile filtered water, ad libitum
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature: 20 ± 1°C
- Humidity: 50-70 %
- Photoperiod: Animals were exposed to artificial light for 10 h daily from 08.00 - 18.00 h
Type of coverage:
occlusive
Preparation of test site:
other: both abraded and intact skin areas lateral to the midline of the back
Vehicle:
water
Controls:
not specified
Amount / concentration applied:
Concentration (if solution): 66.66 %
Duration of treatment / exposure:
24 h
Observation period:
Up to 72 h (The skin reactions were assessed at 24 and 72 h)
Number of animals:
6
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 24 and 72 hours
Score:
0
Reversibility:
fully reversible
Remarks on result:
other: not irritating





Estimation method: Takes mode value from the 6 nearest neighbours
Domain  logical expression:Result: In Domain

((((("a" or "b" or "c" or "d" or "e" or "f" or "g" )  and ("h" and ( not "i") )  )  and ("j" and ( not "k") )  )  and "l" )  and ("m" and "n" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Moderate reactive AND Moderate reactive >> Activated 1,3,5-triazine derivatives AND Not possible to classify according to these rules by DPRA Cysteine peptide depletion

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as SN1 AND SN1 >> Nitrenium Ion formation AND SN1 >> Nitrenium Ion formation >> Aromatic phenylureas by DNA binding by OECD

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Moderate reactive AND Moderate reactive >> Activated 1,3,5-triazine derivatives by DPRA Cysteine peptide depletion

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as High reactive AND High reactive >> Activated 1,3,5-triazine derivatives by DPRA Lysine peptide depletion

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Michael addition AND Michael addition >> Michael addition on polarised Alkenes AND Michael addition >> Michael addition on polarised Alkenes >> Polarised Alkenes - sulfones  AND SNAr AND SNAr >> Nucleophilic aromatic substitution on activated aryl and heteroaryl compounds AND SNAr >> Nucleophilic aromatic substitution on activated aryl and heteroaryl compounds >> Activated aryl and heteroaryl compounds by Protein binding by OASIS v1.4

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Michael addition AND Michael addition >> Polarised Alkenes AND Michael addition >> Polarised Alkenes >> Polarised alkene - sulfinyl AND Michael addition >> Polarised Alkenes >> Polarised alkene - sulfone AND SNAr AND SNAr >> Nucleophilic aromatic substitution AND SNAr >> Nucleophilic aromatic substitution >> Halo-triazines by Protein binding by OECD

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Highly reactive (GSH) AND Highly reactive (GSH) >> Phenyl vinyl sulfone (MA) by Protein binding potency

Domain logical expression index: "h"

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

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Non binder, without OH or NH2 group by Estrogen Receptor Binding

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Michael addition AND Michael addition >> Michael addition on polarised Alkenes AND Michael addition >> Michael addition on polarised Alkenes >> Polarised Alkenes - sulfones  AND SNAr AND SNAr >> Nucleophilic aromatic substitution on activated aryl and heteroaryl compounds AND SNAr >> Nucleophilic aromatic substitution on activated aryl and heteroaryl compounds >> Activated aryl and heteroaryl compounds by Protein binding by OASIS v1.4

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Michael-type addition to quinoid structures  OR AN2 >> Michael-type addition to quinoid structures  >> Quinoneimine OR AN2 >> Michael-type addition to quinoid structures  >> Substituted Anilines OR Nucleophilic addition OR Nucleophilic addition >> Addition to carbon-hetero double bonds OR Nucleophilic addition >> Addition to carbon-hetero double bonds >> Ketones by Protein binding by OASIS v1.4

Domain logical expression index: "l"

Similarity boundary:Target: C=CS(=O)(=O)c1ccc(Nc2nc(Nc3ccc(N=Nc4cc5c(cc4S(O)(=O)=O)cc(S(O)(=O)=O)cc5S(O)(=O)=O)c(NC(N)=O)c3)nc(Cl)n2)cc1
Threshold=50%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "m"

Parametric boundary:The target chemical should have a value of log Kow which is >= -2.99

Domain logical expression index: "n"

Parametric boundary:The target chemical should have a value of log Kow which is <= 0.624

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test substance 1,3,6-Naphthalenetrisulfonic acid, 7-((2-((aminocarbonyl)amino)-4-((4-chloro-6-((4-(ethenylsulfonyl)phenyl)amino)-1,3,5-triazin-2-yl)amino)phenyl)azo)-, sodium salt is estimated to be not irritating to skin of New Zealand White rabbit.
Executive summary:
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The skin irritation potential for 1,3,6-Naphthalenetrisulfonic acid, 7-((2-((aminocarbonyl)amino)-4 -((4-chloro-6- ((4- (ethenylsulfonyl)phenyl)amino) -1,3,5-triazin-2-yl)amino)phenyl)azo)-, sodium salt is estimated using OECD QSAR toolbox version 3.3. The test substance 1,3,6- Naphthalenetrisulfonic acid, 7-((2-((aminocarbonyl)amino) -4-((4-chloro-6- ((4- (ethenylsulfonyl) phenyl)amino) -1,3,5-triazin-2-yl) amino)phenyl)azo)-, sodium salt is estimated to be not irritating to skin of New Zealand White rabbit.

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:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: data from QSAR prediction
Justification for type of information:
QSAR prediction: migrated from IUCLID 5.6
Qualifier:
equivalent or similar to guideline
Guideline:
other: predicted data
Principles of method if other than guideline:
Prediction is done using QSAR Toolbox version 3.3
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Vehicle:
unchanged (no vehicle)
Amount / concentration applied:
100 mg
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
3
Irritation parameter:
iris score
Basis:
mean
Time point:
other: overall at 24, 48 and 72hours
Score:
0
Remarks on result:
other: max level of irritation
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: overall 24, 48 and 72 hours
Score:
0
Remarks on result:
other: max level of irritation
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: overall 24, 48 and 72 hours
Score:
0
Remarks on result:
other: max level of irritation

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

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

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Moderate reactive AND Moderate reactive >> Activated 1,3,5-triazine derivatives AND Not possible to classify according to these rules by DPRA Cysteine peptide depletion

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as SN1 AND SN1 >> Nitrenium Ion formation AND SN1 >> Nitrenium Ion formation >> Aromatic phenylureas by DNA binding by OECD

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Moderate reactive AND Moderate reactive >> Activated 1,3,5-triazine derivatives by DPRA Cysteine peptide depletion

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as High reactive AND High reactive >> Activated 1,3,5-triazine derivatives by DPRA Lysine peptide depletion

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Michael addition AND Michael addition >> Michael addition on polarised Alkenes AND Michael addition >> Michael addition on polarised Alkenes >> Polarised Alkenes - sulfones  AND SNAr AND SNAr >> Nucleophilic aromatic substitution on activated aryl and heteroaryl compounds AND SNAr >> Nucleophilic aromatic substitution on activated aryl and heteroaryl compounds >> Activated aryl and heteroaryl compounds by Protein binding by OASIS v1.4

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Michael addition AND Michael addition >> Polarised Alkenes AND Michael addition >> Polarised Alkenes >> Polarised alkene - sulfinyl AND Michael addition >> Polarised Alkenes >> Polarised alkene - sulfone AND SNAr AND SNAr >> Nucleophilic aromatic substitution AND SNAr >> Nucleophilic aromatic substitution >> Halo-triazines by Protein binding by OECD

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Highly reactive (GSH) AND Highly reactive (GSH) >> Phenyl vinyl sulfone (MA) by Protein binding potency

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.4

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >>  Michael-type addition, quinoid structures OR AN2 >>  Michael-type addition, quinoid structures >> Quinoneimines OR AN2 >> Schiff base formation by aldehyde formed after metabolic activation OR AN2 >> Schiff base formation by aldehyde formed after metabolic activation >> Geminal Polyhaloalkane Derivatives OR Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> Fused-Ring Primary Aromatic Amines OR Radical OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Fused-Ring Primary Aromatic Amines OR Radical >> Radical mechanism via ROS formation (indirect) >> Geminal Polyhaloalkane Derivatives OR Radical >> ROS formation after GSH depletion (indirect) OR Radical >> ROS formation after GSH depletion (indirect) >> Quinoneimines OR SN1 OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Fused-Ring Primary Aromatic Amines OR SN2 OR SN2 >> Acylation involving a leaving group after metabolic activation OR SN2 >> Acylation involving a leaving group after metabolic activation >> Geminal Polyhaloalkane Derivatives OR SN2 >> Nucleophilic substitution at sp3 carbon atom after thiol (glutathione) conjugation OR SN2 >> Nucleophilic substitution at sp3 carbon atom after thiol (glutathione) conjugation >> Geminal Polyhaloalkane Derivatives by DNA binding by OASIS v.1.4

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Moderate reactive AND Moderate reactive >> Activated 1,3,5-triazine derivatives by DPRA Cysteine peptide depletion

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Not possible to classify according to these rules by DPRA Cysteine peptide depletion

Domain logical expression index: "l"

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

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Alkali Earth OR Transition Metals by Groups of elements

Domain logical expression index: "n"

Similarity boundary:Target: C=CS(=O)(=O)c1ccc(Nc2nc(Nc3ccc(N=Nc4cc5c(cc4S(O)(=O)=O)cc(S(O)(=O)=O)cc5S(O)(=O)=O)c(NC(N)=O)c3)nc(Cl)n2)cc1
Threshold=60%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "o"

Parametric boundary:The target chemical should have a value of log Kow which is >= -1.93

Domain logical expression index: "p"

Parametric boundary:The target chemical should have a value of log Kow which is <= 3.25

Interpretation of results:
not irritating
Conclusions:
The substance, 1,3,6-naphthalenetrisulfonic acid, 7-[[2-[(aminocarbonyl)amino]-4-[[4-chloro-6-[[4-(ethenylsulfonyl)phenyl]amino]-1,3,5-triazin-2-yl]amin o]phenyl]azo]-, sodium salt was estimated to be non- irritating to rabbit eyes.
Executive summary:

The ocular irritation potential of 1,3,6-naphthalenetrisulfonic acid, 7-[[2-[(aminocarbonyl)amino]-4-[[4-chloro-6-[[4-(ethenylsulfonyl)phenyl]amino]-1,3,5-triazin-2-yl]amin o]phenyl]azo]-, sodium salt was predicted using OECD QSAR toolbox version 3.3

The substance, 1,3,6-naphthalenetrisulfonic acid, 7-[[2-[(aminocarbonyl)amino]-4-[[4-chloro-6-[[4-(ethenylsulfonyl)phenyl]amino]-1,3,5-triazin-2-yl]amin o]phenyl]azo]-, sodium salt was estimated to be non- irritating to rabbit eyes.

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 for 1,3,6-Naphthalenetrisulfonic acid, 7-((2-((aminocarbonyl)amino)-4 -((4-chloro-6- ((4- (ethenylsulfonyl)phenyl)amino) -1,3,5-triazin-2-yl)amino)phenyl)azo)-, sodium salt is estimated using OECD QSAR toolbox version 3.3. The test substance 1,3,6- Naphthalenetrisulfonic acid, 7-((2-((aminocarbonyl)amino) -4-((4-chloro-6- ((4- (ethenylsulfonyl) phenyl)amino) -1,3,5-triazin-2-yl) amino)phenyl)azo)-, sodium salt is estimated to be not irritating to skin of New Zealand White rabbit.

 

 

Based on the QSAR prediction done using the Danish (Q)SAR Database, the skin irritation was estimated to be negative on rabbits for 7-[[2-[(aminocarbonyl)amino]-4-[[4-chloro-6-[[4-[vinylsulphonyl]phenyl]amino]-1,3,5-triazin-2-yl]amino]phenyl]azo]naphthalene-1,3,6-trisulphonic acid, sodium salt. Thus it can be concluded that the substance 7-[[2-[(aminocarbonyl) amino]-4-[[4-chloro-6-[[4 -[vinylsulphonyl]phenyl]amino]- 1,3,5- triazin-2-yl]amino]phenyl]azo]naphthalene-1,3,6-trisulphonic acid, sodium salt has negative skin irritation effects and it can be classified as not irritant to skin.

On the basis of available information for the target and applying weight of evidence approach, the test substance can be considered as not irritating to the skin.

Eye Irritation:

The ocular irritation potential of 1,3,6-naphthalenetrisulfonic acid,7-[[2-[(aminocarbonyl)amino]- 4-[[4-chloro-6-[[4-(ethenylsulfonyl) phenyl]amino]-1,3,5-triazin-2-yl] amin o]phenyl]azo]-, sodium salt was predicted using OECD QSAR toolbox version 3.3The substance, 1,3,6-naphthalenetrisulfonic acid, 7-[[2-[(aminocarbonyl)amino]-4-[[4-chloro-6-[[4-(ethenylsulfonyl)phenyl]amino]-1,3,5-triazin-2-yl]amin o]phenyl]azo]-, sodium salt was estimated to be non- irritating to rabbit eyes.

On the basis of available information for the target, the test substance can be considered as not irritating to the eye

Justification for selection of skin irritation / corrosion endpoint:

The skin irritation potential for 1,3,6-Naphthalenetrisulfonic acid, 7-((2-((aminocarbonyl)amino)-4 -((4-chloro-6- ((4- (ethenylsulfonyl)phenyl)amino) -1,3,5-triazin-2-yl)amino)phenyl)azo)-, sodium salt is estimated using OECD QSAR toolbox version 3.3. The test substance 1,3,6- Naphthalenetrisulfonic acid, 7-((2-((aminocarbonyl)amino) -4-((4-chloro-6- ((4- (ethenylsulfonyl) phenyl)amino) -1,3,5-triazin-2-yl) amino)phenyl)azo)-, sodium salt is estimated to be not irritating to skin of New Zealand White rabbit.

Justification for selection of eye irritation endpoint:

The ocular irritation potential of 1,3,6-naphthalenetrisulfonic acid, 7-[[2-[(aminocarbonyl)amino]-4-[[4-chloro-6-[[4-(ethenylsulfonyl)phenyl]amino]-1,3,5-triazin-2-yl]amin o]phenyl]azo]-, sodium salt was predicted using OECD QSAR toolbox version 3.3.

The substance, 1,3,6-naphthalenetrisulfonic acid, 7-[[2-[(aminocarbonyl)amino]-4-[[4-chloro-6-[[4-(ethenylsulfonyl)phenyl]amino]-1,3,5-triazin-2-yl]amin o]phenyl]azo]-, sodium salt was estimated to be non- irritating to rabbit eyes.

Justification for classification or non-classification

The test substance1,3,6-Naphthalenetrisulfonic acid, 7-((2-((aminocarbonyl)amino)-4-((4-chloro-6-((4- (ethenylsulfonyl)phenyl)amino) -1,3,5- triazin-2-yl) amino)phenyl)azo)-, sodium saltcan be classified as non- irritant to both skin and eye.