Dihydrogen (ethyl)[4-[4-[ethyl(3-sulphonatobenzyl)amino](4-hydroxy-2-sulphonatobenzhydrylidene]cyclohexa-2,5-dien-1-ylidene](3-sulphonatobenzyl)ammonium, disodium salt

Endpoint summary

Description of key information

Acute toxicity: Oral 
The median lethal dose (LD50) value for dihydrogen (ethyl)[4-[4-[ethyl(3-sulphonatobenzyl)amino](4-hydroxy-2-sulphonatobenzhydrylidene]cyclohexa-2,5-dien-1-ylidene](3-sulphonatobenzyl)ammonium, disodium salt is estimated to be 5404.28 mg/kg in rats by oral administration. This value indicates that the substance is not likely to be toxic by oral route as per the CLP criteria.
Acute toxicity: Dermal 
The median lethal dose (LD50) value for dihydrogen (ethyl)[4-[4-[ethyl(3-sulphonatobenzyl)amino](4-hydroxy-2-sulphonatobenzhydrylidene]cyclohexa-2,5-dien-1-ylidene](3-sulphonatobenzyl)ammonium, disodium salt is estimated to be 2166.13 mg/kg in rats by dermal exposure. This value indicates that the substance is not likely to be toxic by dermal route as per the CLP criteria. 

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

(Q)SAR

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Data is from OECD recommended QSAR toolbox

Justification for type of information:

QSAR prediction: migrated from IUCLID 5.6

Qualifier:

according to guideline

Guideline:

other: as below

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.3

GLP compliance:

no

Test type:

other: estimation

Limit test:

no

Species:

rat

Strain:

other: Tif:RAif (SPF)

Sex:

male/female

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Remarks:

400

Doses:

No data available

No. of animals per sex per dose:

5 animals/sex

Control animals:

not specified

Sex:

male/female

Dose descriptor:

LD50

Effect level:

5 404.288 mg/kg bw

Based on:

test mat.

The prediction was based on dataset comprised from the following descriptors: LD50
Estimation method: Takes average value from the 5 nearest neighbours
Domain  logical expression:Result: In Domain

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

Domain logical expression index: "a"

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

Domain logical expression index: "b"

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

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as No alert found by Protein binding by OECD

Domain logical expression index: "d"

Similarity boundary:Target: CCN(Cc1cccc(S(=O)(=O)O{-}.[Na]{+})c1)c1ccc(C(=C2C=CC(=N{+}(CC)Cc3cccc(S(=O)(=O)O{-})c3)C=C2)c2ccc(O)cc2S(=O)(=O)O{-}.[Na]{+})cc1
Threshold=10%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Not bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "f"

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

Domain logical expression index: "g"

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

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.3

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 >> Quinones OR Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> Amino Anthraquinones OR Non-covalent interaction >> DNA intercalation >> Fused-Ring Primary Aromatic Amines OR Non-covalent interaction >> DNA intercalation >> Quinones OR Non-specific OR Non-specific >> Incorporation into DNA/RNA, due to structural analogy with  nucleoside bases    OR Non-specific >> Incorporation into DNA/RNA, due to structural analogy with  nucleoside bases    >> Specific Imine and Thione Derivatives OR Radical OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Amino Anthraquinones OR Radical >> Radical mechanism via ROS formation (indirect) >> Fused-Ring Primary Aromatic Amines OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitro Azoarenes OR Radical >> Radical mechanism via ROS formation (indirect) >> Quinones OR Radical >> Radical mechanism via ROS formation (indirect) >> Specific Imine and Thione Derivatives OR SN1 OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Amino Anthraquinones OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Fused-Ring Primary Aromatic Amines OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitro Azoarenes OR SN1 >> Nucleophilic substitution on diazonium ions OR SN1 >> Nucleophilic substitution on diazonium ions >> Specific Imine and Thione Derivatives by DNA binding by OASIS v.1.3

Domain logical expression index: "j"

Parametric boundary:The target chemical should have a value of log Kow which is >= -4.52

Domain logical expression index: "k"

Parametric boundary:The target chemical should have a value of log Kow which is <= -1.58

Interpretation of results:

not classified

Remarks:

Migrated informationCriteria used for interpretation of results: EU

Conclusions:

The median lethal dose (LD50) value for dihydrogen (ethyl)[4-[4-[ethyl(3-sulphonatobenzyl)amino](4-hydroxy-2-sulphonatobenzhydrylidene]cyclohexa-2,5-dien-1-ylidene](3-sulphonatobenzyl)ammonium, disodium salt is estimated to be 5404.28 mg/kg in rats.

Executive summary:

The median lethal dose (LD50) value for dihydrogen (ethyl)[4-[4-[ethyl(3-sulphonatobenzyl)amino](4-hydroxy-2-sulphonatobenzhydrylidene]cyclohexa-2,5-dien-1-ylidene](3-sulphonatobenzyl)ammonium, disodium salt is estimated to be 5404.28 mg/kg in rats by oral administration. This value indicates that the substance is not likely to be toxic by oral route as per the CLP criteria.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 404.28 mg/kg bw

Quality of whole database:

Data is from OECD recommended QSAR toolbox

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

(Q)SAR

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Data is from OECD recommended QSAR toolbox

Justification for type of information:

QSAR prediction: migrated from IUCLID 5.6

Qualifier:

according to guideline

Guideline:

other: as below

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.3

GLP compliance:

no

Test type:

other: estimation

Limit test:

no

Species:

rat

Strain:

not specified

Sex:

male/female

Type of coverage:

occlusive

Vehicle:

other: fresh suspension with gum arabic 1% / tap water

Duration of exposure:

24 hours

Doses:

no data

No. of animals per sex per dose:

3 males and 3 females.

Control animals:

not specified

Sex:

male/female

Dose descriptor:

LD50

Effect level:

2 166.131 mg/kg bw

Based on:

test mat.

The prediction was based on dataset comprised from the following descriptors: LD50
Estimation method: Takes average value from the 5 nearest neighbours
Domain  logical expression:Result: In Domain

((((((((("a" or "b" or "c" )  and "d" )  and ("e" and ( not "f") )  )  and ("g" and ( not "h") )  )  and "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 SN1 AND SN1 >> Nitrenium Ion formation AND SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine by DNA binding by OECD

Domain logical expression index: "b"

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

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as No alert found by Protein binding by OECD

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Not bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "e"

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

Domain logical expression index: "f"

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

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Group 1 - Alkali Earth Li,Na,K,Rb,Cs,Fr AND Group 14 - Carbon C AND Group 15 - Nitrogen N AND Group 16 - Oxygen O AND Group 16 - Sulfur S by Chemical elements

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Group 15 - Phosphorus P by Chemical elements

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as High (Class III) by Toxic hazard classification by Cramer (original) ONLY

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.3

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Shiff base formation after aldehyde release OR AN2 >> Shiff base formation after aldehyde release >> Specific Acetate Esters OR Radical OR Radical >> Generation of reactive oxygen species OR Radical >> Generation of reactive oxygen species >> Thiols OR Radical >> Radical mechanism by ROS formation (indirect) or direct radical attack on DNA OR Radical >> Radical mechanism by ROS formation (indirect) or direct radical attack on DNA >> Organic Peroxy Compounds OR SN1 OR SN1 >> Nucleophilic attack after carbenium ion formation OR SN1 >> Nucleophilic attack after carbenium ion formation >> Specific Acetate Esters OR SN2 OR SN2 >> Acylation OR SN2 >> Acylation >> Specific Acetate Esters OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Specific Acetate Esters by DNA binding by OASIS v.1.3

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Not categorized by OECD HPV Chemical Categories

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as C.I. Fluorescent Brightener 28 113 OR Chelants OR Naphthalene sulfonic acids, condensates OR Propylene glycol ethers by OECD HPV Chemical Categories

Domain logical expression index: "n"

Similarity boundary:Target: CCN(Cc1cccc(S(=O)(=O)O{-}.[Na]{+})c1)c1ccc(C(=C2C=CC(=N{+}(CC)Cc3cccc(S(=O)(=O)O{-})c3)C=C2)c2ccc(O)cc2S(=O)(=O)O{-}.[Na]{+})cc1
Threshold=10%,
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 >= -5.64

Domain logical expression index: "p"

Parametric boundary:The target chemical should have a value of log Kow which is <= -0.104

Interpretation of results:

not classified

Remarks:

Migrated informationCriteria used for interpretation of results: EU

Conclusions:

The median lethal dose (LD50) value for dihydrogen (ethyl)[4-[4-[ethyl(3-sulphonatobenzyl)amino](4-hydroxy-2-sulphonatobenzhydrylidene]cyclohexa-2,5-dien-1-ylidene](3-sulphonatobenzyl)ammonium, disodium salt is estimated to be 2166.13 mg/kg in rats by dermal exposure.

Executive summary:

The median lethal dose (LD50) value for dihydrogen (ethyl)[4-[4-[ethyl(3-sulphonatobenzyl)amino](4-hydroxy-2-sulphonatobenzhydrylidene]cyclohexa-2,5-dien-1-ylidene](3-sulphonatobenzyl)ammonium, disodium salt is estimated to be 2166.13 mg/kg in rats by dermal exposure. This value indicates that the substance is not likely to be toxic by dermal route as per the CLP criteria.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 166.13 mg/kg bw

Quality of whole database:

Data is from OECD recommended QSAR toolbox

Additional information

Acute toxicity: Oral

The median lethal dose (LD50) value for dihydrogen (ethyl)[4-[4-[ethyl(3-sulphonatobenzyl)amino](4-hydroxy-2-sulphonatobenzhydrylidene]cyclohexa-2,5-dien-1-ylidene](3-sulphonatobenzyl)ammonium, disodium salt is estimated to be 5404.28 mg/kg in rats by oral administration. This value indicates that the substance is not likely to be toxic by oral route as per the CLP criteria.

Acute toxicity: Inhalation

This end point was considered for waiver since exposure of humans via inhalation to the chemical FD&C Green is highly unlikely taking into account the extremely low vapour pressure of 1.7E-43 mm Hg at 25 deg C. In addition, the possibility of exposure to inhalable particles is also negligible given the particle size distribution of the chemical which have larger particle size than which can be inhaled. Thus, acute toxicity by the inhalation route appears highly unlikely.

Acute toxicity: Dermal

The median lethal dose (LD50) value for dihydrogen (ethyl)[4-[4-[ethyl(3-sulphonatobenzyl)amino](4-hydroxy-2-sulphonatobenzhydrylidene]cyclohexa-2,5-dien-1-ylidene](3-sulphonatobenzyl)ammonium, disodium salt is estimated to be 2166.13 mg/kg in rats by dermal exposure. This value indicates that the substance is not likely to be toxic by dermal route as per the CLP criteria.

Justification for selection of acute toxicity – oral endpoint
The median lethal dose (LD50) value for dihydrogen (ethyl)[4-[4-[ethyl(3-sulphonatobenzyl)amino](4-hydroxy-2-sulphonatobenzhydrylidene]cyclohexa-2,5-dien-1-ylidene](3-sulphonatobenzyl)ammonium, disodium salt is estimated to be 5404.28 mg/kg in rats by oral administration. This value indicates that the substance is not likely to be toxic by oral route as per the CLP criteria.

Justification for selection of acute toxicity – inhalation endpoint
This end point was considered for waiver since exposure of humans via inhalation to the chemical FD&C Green is highly unlikely taking into account the extremely low vapour pressure of 1.7E-43 mm Hg at 25 deg C. In addition, the possibility of exposure to inhalable particles is also negligible given the particle size distribution of the chemical which have larger particle size than which can be inhaled. Thus, acute toxicity by the inhalation route appears highly unlikely.

Justification for selection of acute toxicity – dermal endpoint
The median lethal dose (LD50) value for dihydrogen (ethyl)[4-[4-[ethyl(3-sulphonatobenzyl)amino](4-hydroxy-2-sulphonatobenzhydrylidene]cyclohexa-2,5-dien-1-ylidene](3-sulphonatobenzyl)ammonium, disodium salt is estimated to be 2166.13 mg/kg in rats by dermal exposure. This value indicates that the substance is not likely to be toxic by dermal route as per the CLP criteria.

Justification for classification or non-classification

From the data available for the target chemical dihydrogen (ethyl)[4-[4-[ethyl(3-sulphonatobenzyl)amino](4-hydroxy-2-sulphonatobenzhydrylidene]cyclohexa-2,5-dien-1-ylidene](3-sulphonatobenzyl)ammonium, disodium salt, it is concluded that the chemical is not likely to exhibit acute toxicity by the oral, inhalation and dermal route of exposure. Thus, the chemical is not classified for acute toxicity by either of the 3 routes of exposure.