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Short-term toxicity to aquatic invertebrates

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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:
The supporting QMRF report has been attached.
Reference:
Composition 1
Qualifier:
according to
Guideline:
other: Estimated data
Principles of method if other than guideline:
The prediction was done by using OECD QSAR tool box v3.3
GLP compliance:
not specified
Test material information:
Composition 1
Specific details on test material used for the study:
- Name of test material: C.I. Basic Violet 2 / (4-[(4-amino-m-tolyl)(4-imino-3-methylcyclohexa-2,5-dien-1-ylidene)methyl]-o-toluidine monohydrochloride)
- IUPAC name: 4-[(4-amino-3-methylphenyl)(4-imino-3-methylcyclohexa-2,5-dien-1-ylidene)methyl]-2-methylaniline hydrochloride
- Molecular formula: C22H24ClN3
- Molecular weight: 365.906 g/mole
- Smiles :C(\c1cc(c(N)cc1)C)(c1cc(c(N)cc1)C)=C1\C=C(C(=[NH+])C=C1)C.[ClH-]
- Inchl: 1S/C22H23N3.ClH/c1-13-10-16(4-7-19(13)23)22(17-5-8-20(24)14(2)11-17)18-6-9-21(25)15(3)12-18;/h4-12,23H,24-25H2,1-3H3;1H
- Substance type: Organic
- Physical state: Solid Green crystalline powder
Vehicle:
not specified
Test organisms (species):
Daphnia magna
Key result
Duration:
48 h
Dose descriptor:
EC50
Effect conc.:
508.66 mg/L
Conc. based on:
test mat.
Basis for effect:
other: Intoxication
Remarks on result:
other: other details not 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" or "e" )  and ("f" and ( not "g") )  )  and ("h" and ( not "i") )  )  and ("j" and ( not "k") )  )  and ("l" and ( not "m") )  )  and ("n" and ( not "o") )  )  and ("p" and ( not "q") )  )  and ("r" and ( not "s") )  )  and "t" )  and ("u" and ( not "v") )  )  and ("w" and ( not "x") )  )  and ("y" and "z" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Anilines (Acute toxicity) AND Dianilines AND Not categorized AND Triarylmethane Pigments/Dyes with Non-solubilizing Groups by US-EPA New Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Amine OR Aromatic compound OR No functional group found OR Primary amine OR Primary aromatic amine by Organic functional groups, Norbert Haider (checkmol) ONLY

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Aliphatic Carbon [CH] OR Aliphatic Carbon [-CH2-] OR Aliphatic Carbon [-CH3] OR Aliphatic Nitrogen, one aromatic attach [-N] OR Aromatic Carbon [C] OR No functional group found OR Olefinic carbon [=CH- or =C<] by Organic functional groups (US EPA) ONLY

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Alkene OR Alkyl arenes OR Allyl OR Dianilines OR Ketimine OR No functional group found OR Overlapping groups OR Precursors quinoid compounds by Organic Functional groups (nested) ONLY

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Alkene OR Alkyl arenes OR Allyl OR Aniline OR Aryl OR Dianilines OR Ketimine OR No functional group found OR Precursors quinoid compounds by Organic Functional groups ONLY

Domain logical expression index: "f"

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: "g"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Carbamoylation after isocyanate formation OR AN2 >> Carbamoylation after isocyanate formation >> N-Hydroxylamines OR AN2 >> Nucleophilic addition to alpha, beta-unsaturated carbonyl compounds OR AN2 >> Nucleophilic addition to alpha, beta-unsaturated carbonyl compounds >> alpha, beta-Unsaturated Aldehydes OR AN2 >> Schiff base formation OR AN2 >> Schiff base formation >> alpha, beta-Unsaturated Aldehydes OR Radical >> Radical mechanism via ROS formation (indirect) >> N-Hydroxylamines OR Radical >> Radical mechanism via ROS formation (indirect) >> p-Aminobiphenyl Analogs OR Radical >> Radical mechanism via ROS formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines OR SN1 >> Alkylation after metabolically formed carbenium ion species OR SN1 >> Alkylation after metabolically formed carbenium ion species >> Polycyclic Aromatic Hydrocarbon Derivatives OR SN1 >> Nucleophilic attack after carbenium ion formation OR SN1 >> Nucleophilic attack after carbenium ion formation >> N-Nitroso Compounds OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> N-Hydroxylamines OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> p-Aminobiphenyl Analogs OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Single-Ring Substituted Primary Aromatic Amines OR SN1 >> Nucleophilic attack after nitrenium and/or carbenium ion formation OR SN1 >> Nucleophilic attack after nitrenium and/or carbenium ion formation >> N-Nitroso Compounds OR SN2 OR SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation OR SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation >> Polycyclic Aromatic Hydrocarbon Derivatives OR SN2 >> Direct acting epoxides formed after metabolic activation OR SN2 >> Direct acting epoxides formed after metabolic activation >> Quinoline Derivatives OR SN2 >> SN2 at an activated carbon atom OR SN2 >> SN2 at an activated carbon atom >> Quinoline Derivatives by DNA binding by OASIS v.1.3

Domain logical expression index: "h"

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

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Michael addition OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Alkyl phenols OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Arenes OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Hydroquinones OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Polycyclic (PAHs) and heterocyclic (HACs) aromatic hydrocarbons-Michael addition OR SN1 >> Carbenium Ion Formation OR SN1 >> Carbenium Ion Formation >> Allyl benzenes OR SN1 >> Iminium Ion Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines by DNA binding by OECD

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Non binder, non cyclic structure AND Strong binder, NH2 group by Estrogen Receptor Binding

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Moderate binder, NH2 group OR Non binder, impaired OH or NH2 group OR Non binder, MW>500 OR Non binder, without OH or NH2 group OR Weak binder, NH2 group OR Weak binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Alkyl substituent on aromatic ring AND Aromatic amine   [-NH2  or  -NH-] AND Aromatic-CH3 AND Aromatic-H AND Benzene AND -C=CH  [alkenyl hydrogen] AND Methyl  [-CH3] AND No alert found by Bioaccumulation - metabolism alerts

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as -CH2-  [linear] OR Cyanide / Nitriles   [-C#N] OR Fluorine  [-F] OR Linear C4 terminal chain  [CCC-CH3] OR N-Alkane (linear) ... < C22 OR Number of fused acyclic rings OR Quaternary amine OR Tin  [Sn] by Bioaccumulation - metabolism alerts

Domain logical expression index: "n"

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

Domain logical expression index: "o"

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

Domain logical expression index: "p"

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

Domain logical expression index: "q"

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

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as ECHA PR AND EINECS AND NICNAS AND REACH ECB AND TSCA by Inventory Affiliation

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as COSING by Inventory Affiliation

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as Mixture by Substance Type ONLY

Domain logical expression index: "u"

Referential boundary: The target chemical should be classified as (N/A) by Database Affiliation

Domain logical expression index: "v"

Referential boundary: The target chemical should be classified as Bacterial mutagenicity ISSSTY by Database Affiliation

Domain logical expression index: "w"

Referential boundary: The target chemical should be classified as (N/A) by Database Affiliation

Domain logical expression index: "x"

Referential boundary: The target chemical should be classified as Experimental pKa OR Micronucleus ISSMIC OR Phys-chem EPISUITE by Database Affiliation

Domain logical expression index: "y"

Parametric boundary:The target chemical should have a value of log Kow which is >= -0.877

Domain logical expression index: "z"

Parametric boundary:The target chemical should have a value of log Kow which is <= 6.24

Validity criteria fulfilled:
not specified
Conclusions:
Short term toxicity of test chemical 4-[(4-amino-3-methylphenyl)(4-imino-3-methylcyclohexa-2,5-dien-1-ylidene)methyl]-2-methylaniline hydrochloride was estimated when test chemical was exposed for 48 hrs on Daphnia magna and EC50 value was estimated to be 508.66 mg/L. Since EC50 value is greater than 100 mg/L it is concluded that this test chemical can be considered to be not classified according to CLP classification criteria.
Executive summary:

Short term toxicity of test chemical 4-[(4-amino-3-methylphenyl)(4-imino-3-methylcyclohexa-2,5-dien-1-ylidene)methyl]-2-methylaniline hydrochloride (CASno. 3248-91-7)  was estimated by using OECD QSAR tool box v3.3 with log Kow as primary descriptor and considering the six closest read across substances. When test chemical was exposed for 48 hrs on Daphnia magna EC50 value was estimated to be 508.66 mg/L. Since EC50 value is greater than 100 mg/L it is concluded that this test chemical can be considered to be not classified according to CLP classification criteria.

Description of key information

Short term toxicity of test chemical 4-[(4-amino-3-methylphenyl)(4-imino-3-methylcyclohexa-2,5-dien-1-ylidene)methyl]-2-methylaniline hydrochloride (CASno. 3248-91-7)  was estimated by using OECD QSAR tool box v3.3 with log Kow as primary descriptor and considering the six closest read across substances. When test chemical was exposed for 48 hrs on Daphnia magna EC50 value was estimated to be 508.66 mg/L. Since EC50 value is greater than 100 mg/L it is concluded that this test chemical can be considered to be not classified according to CLP classification criteria.

Key value for chemical safety assessment

EC50/LC50 for freshwater invertebrates:
508.66 mg/L

Additional information

Two different predicted data studies have been conducted for target chemical

4-[(4-amino-3-methylphenyl)(4-imino-3-methylcyclohexa-2,5-dien-1-ylidene)methyl]-2-methylaniline hydrochloride (CASno. 3248-91-7) and one experimental study conducted for its read across chemical to determine short term toxicity to aquatic invetebrate endpoint and their results are summarized below.

In first weight of evidence predicted data study the short term toxicity of test chemical 4-[(4-amino-3-methylphenyl)(4-imino-3-methylcyclohexa-2,5-dien-1-ylidene)methyl]-2-methylaniline hydrochloride (CASno. 3248-91-7)  was estimated by using OECD QSAR tool box v3.3 with log Kow as primary descriptor and considering the six closest read across substances. When test chemical was exposed for 48 hrs on Daphnia magna EC50 value was estimated to be 508.66 mg/L. Since EC50 value is greater than 100 mg/L it is concluded that this test chemical can be considered to be not classified according to CLP classification criteria.

Another weight of evidence predicted data study done by EPI suite, ECOSAR version 1.1, on the basis of similarity of structure to chemicals for which the aquatic toxicity has been previously measured by structure-activity relationships (SARs) program, the LC 50 value for short term toxicity to aquatic invertebrates was predicted.

On the basis of this program, the LC 50 value for short term toxicity to aquatic invertebrates was predicted to be 385.045 mg/l for test chemical 4-[(4-amino-3-methylphenyl)(4-imino-3-methylcyclohexa-2,5-dien-1-ylidene)methyl]-2-methylaniline hydrochloride (CAS no. 3248-91-7) in 48 hrs.

Based on this value it can be concluded that the substance is considered to be not toxic to aquatic environment and can not be classified in category as per the criteria mentioned in CLP regulation.

Last study was done from authoritative database ( Ecotox. 2017) in this study short term toxicity to Litopenaeus schmitti (Southern white shrimp) was determined for 48 hrs.The study was based on the effects of the read across compound 4 -[(4 -dimethylamino phenyl)-phenylmethylidene]cyclohexa-2,5-dien-1-ylidene]-dimethylazanium chloride (CAS no. 569-64-2) on Litopenaeus schmitti in a static salt water system. Litopenaeus schmitti (Southern white shrimp) was used as a test organism. Based on effect on mortality of the test organism Litopenaeus schmitti, the 48 hr LC50 value was determined to be 77170 mg/L (LC50 value ranges from 60470 to 109120 mg/l).Thus, based on the LC50 value, it can be concluded that the substance 4 -[(4 -dimethylaminophenyl)-phenylmethyli dene]cyclohexa-2,5-dien-1-ylidene]-dimethylazanium chloride can be considered as non-toxic to aquatic organisms and thus can be considered to be not classified as per the CLP classification criteria.

Based on the results of all the studies from different sources mentioned above for target chemical

4-[(4-amino-3-methylphenyl)(4-imino-3-methylcyclohexa-2,5-dien-1-ylidene)methyl]-2-methylaniline hydrochloride (CASno. 3248-91-7) and its read across chemical EC50 value falls in range of 385.045 - 508.66 mg/L and by this range value it is concluded that that test chemical can be considered as not classified according to CLP classification criteria.