9-[2-(ethoxycarbonyl)phenyl]-3,6-bis(ethylamino)-2,7-dimethylxanthylium, salt with 4,5-dihydro-5-oxo-1-(4-sulphophenyl)-4-[(4-sulphophenyl)azo]-1H-pyrazole-3-carboxylic acid (3:1)

Short-term toxicity to aquatic invertebrates

Link to relevant study record(s)

Reference

Endpoint:

short-term toxicity to aquatic invertebrates

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 3.3 and the QMRF report has been attached.

Qualifier:

according to guideline

Guideline:

other: Estimated data

Version / remarks:

No data available

Deviations:

not specified

Principles of method if other than guideline:

Prediction was done using the OECD QSAR toolbox version 3.3.

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material (IUPAC name): 9-[2-(ethoxycarbonyl)phenyl]-3,6-bis(ethylamino)-2,7-dimethylxanthylium
- Molecular formula: C28H31N2O3.1/3C16H9N4O9S2
- Molecular weight: 1796.09 g/mol
- Smiles notation: c1(C)c(cc2[o+]c3c(c(c4c(cccc4)C(OCC)=O)c2c1)cc(C)c(NCC)c3)NCC.C1([C@@H](\N=N/c2ccc(cc2)S([O-])(=O)=O)C(=NN1c1ccc(S([O-])(=O)=O)cc1)C([O-])=O)=O.c1(cc2c([o+]c3c(c2c2ccccc2C(OCC)=O)cc(c(NCC)c3)C)cc1NCC)C.c1(cc2c([o+]c3c(c2c2ccccc2C(OCC)=O)cc(c(NCC)c3)C)cc1NCC)C
- InChl: 1S/3C28H31N2O3.C16H12N4O9S2/c3*1-6-29-23-15-25-21(13-17(23)4)27(19-11-9-10-12-20(19)28(31)32-8-3)22-14-18(5)24(30-7-2)16-26(22)33-25;21-15-13(18-17-9-1-5-11(6-2-9)30(24,25)26)14(16(22)23)19-20(15)10-3-7-12(8-4-10)31(27,28)29/h3*9-16,29-30H,6-8H2,1-5H3;1-8,13H,(H,22,23)(H,24,25,26)(H,27,28,29)/q3*+1;/p-3/b;;;18-17-
- Substance type: Organic
- Physical state: Solid

Analytical monitoring:

not specified

Details on sampling:

No data available

Vehicle:

not specified

Details on test solutions:

No data available

Test organisms (species):

Daphnia magna

Details on test organisms:

- Common name: Water flea

Test type:

static

Water media type:

freshwater

Limit test:

no

Total exposure duration:

48 h

Remarks on exposure duration:

No data available

Post exposure observation period:

No data available

Hardness:

2.502 mmol/L

Test temperature:

20.7 - 22.0°C

pH:

7.95 - 8.28

Dissolved oxygen:

5.5 - 6.2 mg/L

Salinity:

No data available

Conductivity:

No data available

Nominal and measured concentrations:

No data available

Details on test conditions:

No data available

Reference substance (positive control):

not specified

Key result

Duration:

48 h

Dose descriptor:

EC50

Effect conc.:

117.564 mg/L

Nominal / measured:

estimated

Conc. based on:

test mat.

Basis for effect:

mobility

Remarks on result:

other: Non toxic to aquatic invertebrates

Details on results:

No data available

Results with reference substance (positive control):

No data available

Reported statistics and error estimates:

No data available

The prediction was based on dataset comprised from the following descriptors: EC50
Estimation method: Takes average value from the 6 nearest neighbours
Domain  logical expression:Result: In Domain

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

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Esters (Chronic toxicity) AND Not categorized by US-EPA New Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as No alert found AND Non-specific AND Non-specific >> Incorporation into DNA/RNA, due to structural analogy with  nucleoside bases    AND Non-specific >> Incorporation into DNA/RNA, due to structural analogy with  nucleoside bases    >> Specific Imine and Thione Derivatives AND Radical AND Radical >> Radical mechanism via ROS formation (indirect) AND Radical >> Radical mechanism via ROS formation (indirect) >> Specific Imine and Thione Derivatives AND SN1 AND SN1 >> Nucleophilic substitution on diazonium ions AND SN1 >> Nucleophilic substitution on diazonium ions >> Specific Imine and Thione Derivatives by DNA binding by OASIS v.1.3

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as No alert found AND SN1 AND SN1 >> Nitrenium Ion formation AND SN1 >> Nitrenium Ion formation >> Secondary aromatic amine by DNA binding by OECD

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Esters OR Inorganic Compound OR Schiff Bases-Azomethine OR Vinyl/Allyl Ethers by Aquatic toxicity classification by ECOSAR ONLY

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as No alert found by Protein binding by OASIS v1.3

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Ester aminolysis OR Acylation >> Ester aminolysis >> Amides OR Acylation >> Ester aminolysis or thiolysis OR Acylation >> Ester aminolysis or thiolysis >> Activated aryl esters  OR Acylation >> Ring opening acylation OR Acylation >> Ring opening acylation >> Active cyclic agents  OR Michael Addition OR Michael Addition >> Michael addition on conjugated systems with electron withdrawing group OR Michael Addition >> Michael addition on conjugated systems with electron withdrawing group >> alpha,beta-Carbonyl compounds with polarized double bonds  OR Nucleophilic addition OR Nucleophilic addition >> Addition to carbon-hetero double bonds OR Nucleophilic addition >> Addition to carbon-hetero double bonds >> Ketones OR SN2 OR SN2 >> Nucleophilic substitution at sp3 carbon atom OR SN2 >> Nucleophilic substitution at sp3 carbon atom >> Alkyl halides  OR SN2 >> Nucleophilic substitution at sp3 carbon atom >> Sulfates  OR SN2 >> Nucleophilic substitution at sp3 carbon atom >> Sulfonates OR SN2 >> Ring opening SN2 reaction OR SN2 >> Ring opening SN2 reaction >> Sultones OR SN2 >> SN2 Reaction at a sp3 carbon atom OR SN2 >> SN2 Reaction at a sp3 carbon atom >> Activated alkyl esters and thioesters  OR SNAr OR SNAr >> Nucleophilic aromatic substitution on activated aryl and heteroaryl compounds OR SNAr >> Nucleophilic aromatic substitution on activated aryl and heteroaryl compounds >> Activated aryl and heteroaryl compounds by Protein binding by OASIS v1.3

Domain logical expression index: "g"

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

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Alkyl substituent on aromatic ring AND Aromatic amine   [-NH2  or  -NH-] AND Aromatic ether  [-O-aromatic carbon] AND Aromatic-CH AND Aromatic-CH3 AND Aromatic-H AND Benzene AND -CH2-  [linear] AND Ester   [-C(=O)-O-C] AND Methyl  [-CH3] AND Number of fused 6-carbon aromatic rings AND Polycyclic -CH3 (3 fused rings or less) by Bioaccumulation - metabolism alerts

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Linear C4 terminal chain  [CCC-CH3] by Bioaccumulation - metabolism alerts

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Alkyl substituent on aromatic ring AND Aromatic amine   [-NH2  or  -NH-] AND Aromatic ether  [-O-aromatic carbon] AND Aromatic-CH AND Aromatic-CH3 AND Aromatic-H AND Benzene AND -CH2-  [linear] AND Ester   [-C(=O)-O-C] AND Methyl  [-CH3] AND Number of fused 6-carbon aromatic rings AND Polycyclic -CH3 (3 fused rings or less) by Bioaccumulation - metabolism alerts

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Unsubstituted Cycloalkane by Bioaccumulation - metabolism alerts

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Esters by Aquatic toxicity classification by ECOSAR ONLY

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Alkyl substituent on aromatic ring AND Aromatic amine   [-NH2  or  -NH-] AND Aromatic ether  [-O-aromatic carbon] AND Aromatic-CH AND Aromatic-CH3 AND Aromatic-H AND Benzene AND -CH2-  [linear] AND Ester   [-C(=O)-O-C] AND Methyl  [-CH3] AND Number of fused 6-carbon aromatic rings AND Polycyclic -CH3 (3 fused rings or less) by Bioaccumulation - metabolism alerts

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Naphthalene OR No alert found by Bioaccumulation - metabolism alerts

Domain logical expression index: "o"

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

Domain logical expression index: "p"

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

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Alkyl arenes AND Aromatic amine AND Aryl AND Carboxylic acid ester AND Fused carbocyclic aromatic AND Fused saturated heterocycles AND Xanthene by Organic Functional groups

Domain logical expression index: "r"

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

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as Alkyl arenes AND Aromatic amine AND Aryl AND Carboxylic acid ester AND Fused carbocyclic aromatic AND Fused saturated heterocycles AND Xanthene by Organic Functional groups

Domain logical expression index: "t"

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

Domain logical expression index: "u"

Referential boundary: The target chemical should be classified as Alkyl arenes AND Aromatic amine AND Aryl AND Carboxylic acid ester AND Fused carbocyclic aromatic AND Fused saturated heterocycles AND Xanthene by Organic Functional groups

Domain logical expression index: "v"

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

Domain logical expression index: "w"

Referential boundary: The target chemical should be classified as Alkyl arenes AND Aromatic amine AND Aryl AND Carboxylic acid ester AND Fused carbocyclic aromatic AND Fused saturated heterocycles AND Xanthene by Organic Functional groups

Domain logical expression index: "x"

Referential boundary: The target chemical should be classified as tert-Butyl by Organic Functional groups

Domain logical expression index: "y"

Referential boundary: The target chemical should be classified as Alkyl arenes AND Aromatic amine AND Aryl AND Carboxylic acid ester AND Fused carbocyclic aromatic AND Fused saturated heterocycles AND Xanthene by Organic Functional groups

Domain logical expression index: "z"

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

Domain logical expression index: "aa"

Parametric boundary:The target chemical should have a value of log Kow which is >= 2.67

Domain logical expression index: "ab"

Parametric boundary:The target chemical should have a value of log Kow which is <= 8.73

Validity criteria fulfilled:

not specified

Conclusions:

Based on the immobility of daphnia magna due to the exposure of chemical 9-[2-(ethoxycarbonyl)phenyl]-3,6-bis(ethylamino)-2,7-dimethylxanthylium for 48 hrs, the EC50 was 117.563 mg/l.

Executive summary:

Based on the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the six closest read across substances, toxicity on daphnia magna was predicted for 9-[2-(ethoxycarbonyl)phenyl]-3,6-bis(ethylamino) -2,7- dimethylxanthylium.The EC50 value was estimated to be 117.563 mg/l when 9-[2-(ethoxycarbonyl)phenyl]-3,6-bis(ethylamino)-2,7- dimethyl -xanthylium exposed to daphnia magna for 48 hrs.

Description of key information

Based on the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the six closest read across substances, toxicity on daphnia magna was predicted for 9-[2-(ethoxycarbonyl)phenyl]-3,6-bis(ethylamino) -2,7- dimethylxanthylium.The EC50 value was estimated to be 117.563 mg/l when 9-[2-(ethoxycarbonyl)phenyl]-3,6-bis(ethylamino)-2,7- dimethyl -xanthylium exposed to daphnia magna for 48 hrs.

Key value for chemical safety assessment

Fresh water invertebrates

Fresh water invertebrates

Effect concentration:

117.563 mg/L

Additional information

Summarized result of toxicity of the chemical 9-[2-(ethoxycarbonyl)phenyl]-3,6-bis(ethylamino)-2,7-dimethylxanthylium on the growth of aquatic invertebrates are as mention below:

In the first weight of evidence study from QSAR, 2017 for target chemical has been consider,based on the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the six closest read across substances, toxicity on daphnia magna was predicted for 9-[2-(ethoxycarbonyl)phenyl]-3,6-bis(ethylamino)-2,7-dimethylxanthylium.The EC50 value was estimated to be 117.563 mg/l when 9-[2-(ethoxycarbonyl)phenyl]-3,6-bis(ethylamino)-2,7-dimethylxanthylium exposed to daphnia magna for 48 hrs.

 

In the second weight of evidence study for (518-47-8) from ABITEC report 2017, Determination of the inhibition of the mobility of daphnids was carried out with the substance Disodium 2-(3-oxo-6-oxidoxanthen-9-yl) benzoate according to OECD Guideline 202. A limit test at sample concentration of 100 mg/L was performed. Effects on immobilisation were observed for 48 hours. The median effective concentration (EC50) for the test substance, Disodium 2-(3-oxo-6-oxidoxanthen-9-yl)benzoate, in Daphnia magna was determined to be >100 mg/L for immobilisation effects. Based on this EC50 value and after comparing with CLP criteria for aquatic classification of the substance it is concluded that the substance, Disodium 2-(3-oxo-6-oxidoxanthen-9-yl)benzoate does not exhibit short term toxicity to aquatic invertebrate (Daphnia Magna).

 

Similarly in the third weight of evidence study for same RA chemical (518 -47 -8) 1995, Ecological assessments included both acute and chronic effects for the 3 life forms: fish, Cladocera (water flea, daphnia), and algae. The concern levels identified by use of the SAR technique are expressed ad HIGH, MODERATE, LOW. These values are toxicity values, not exposure values. SAR results are generally regarded by EPA as being reliable. Dyes with aquatic toxicity values below 1mg/l received a HIGH concern rating, those with toxicity values ranging from 1-100mg/l received a MODERATE concern rating and those with toxicity values greater than 100mg/l received a LOW concern rating. The Median Lethal Concentration which is estimated to be lethal to 50% of Cladocera (water flea) in 48 hours exposure to the test chemical (LC50) was 165mg/l. Since the LC50 for the test chemical was determined to be 165 mg/l, it falls in the low concern category in the aquatic toxicity ratings. Thus, based on the result according to the CLP regulation it was considered that the test chemical was not classified to short term aquatic invertebrates.

 

 

Similarly in the fourth weight of evidence study for another RA chemical (502-33-4) OECD SIDS 2004, Short term toxicity of Caprolactone on the growth of daphnia magna was studied by the exposure of chemical with the daphnia for 48 hrs. Test was performed according to the OECD guideline. Daphnia expose for 48 hrs under the proper conditions of temperature and ph.500.1 mg epsilon caprolactone was stirred in 500 ml M4 medium for about 10 minutes at 20 degrees C resulting in a stock solution of 1000 mg/l. Then different concentration and control was prepared. 0, 62.5, 125, 250, 500 and 1000 mg/l concentration was prepared for the study. After the exposure of 48 hrs. The various effect concentration was observed EC0 was 125 mg/l, EC50 was 204 mg/l and the EC100 was 500 mg/l. Based on the immobility of daphnia magna due to the exposure of chemical Caprolactone for 48 hrs, the EC50 was 204 mg/l. Thus the chemical was consider as non-toxic and can be consider to be not classified as toxic as per the CLP classification criteria.

 

Thus based on the various studies it was concluded that the chemical 9-[2-(ethoxycarbonyl)phenyl]-3,6-bis(ethylamino)-2,7-dimethylxanthylium (65138-66-1) was consider as non-toxic and can be consider to be not classified as toxic as per the CLP classification criteria.