(4-(4-aminophenyl)(4-iminocyclohexa-2,5-dienylidene)methyl)-2-methylaniline hydrochloride

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:

The supporting QMRF report has been attached

Qualifier:

according to

Guideline:

other: as mentioned below

Principles of method if other than guideline:

Prediction is done using OECD QSAR Toolbox version 3.3 with logKow as the primary descriptor.

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material (IUPAC name): (4-(4-aminophenyl)(4-iminocyclohexa-2,5-dienylidene)methyl)-2-methylaniline hydrochloride
- Common name: Fuschine
- Molecular formula: C20H19N3.HCl
- Molecular weight: 337.852
- Smiles notation: C(\c1cc(c(N)cc1)C)(c1ccc(N)cc1)=C1/C=CC(=N)C=C1.Cl
- InChl: 1S/C20H19N3.ClH/c1-13-12-16(6-11-19(13)23)20(14-2-7-17(21)8-3-14)15-4-9-18(22)10-5-15;/h2-12,21H,22-23H2,1H3;1H/b20-14-,21-17?;
- Substance type: Organic
- Physical state: Solid

Analytical monitoring:

not specified

Vehicle:

not specified

Test organisms (species):

Daphnia magna

Test type:

static

Water media type:

freshwater

Total exposure duration:

48 h

Test temperature:

21-21.2°C

pH:

7.9

Reference substance (positive control):

not specified

Key result

Duration:

48 h

Dose descriptor:

EC50

Effect conc.:

222.81 mg/L

Nominal / measured:

estimated

Conc. based on:

test mat.

Basis for effect:

other: Intoxication

The prediction was based on dataset comprised from the following descriptors: EC50
Estimation method: Takes average value from the 7 nearest neighbours
Domain  logical expression:Result: In Domain

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

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 Alkene OR Allyl OR Aniline OR Aryl OR Dianilines OR Ketimine OR No functional group found by Organic Functional groups ONLY

Domain logical expression index: "c"

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

Domain logical expression index: "d"

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: "e"

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: "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 ONLY

Domain logical expression index: "g"

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: "h"

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 >> Arenes OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Polycyclic (PAHs) and heterocyclic (HACs) aromatic hydrocarbons-Michael addition OR SN1 >> Iminium Ion Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines by DNA binding by OECD

Domain logical expression index: "i"

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: "j"

Referential boundary: The target chemical should be classified as 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 by Estrogen Receptor Binding

Domain logical expression index: "k"

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

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 Alkaline Earth OR Metalloids OR Metals OR Rare Earth OR Transition Metals by Groups of elements

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Group 14 - Carbon C AND Group 15 - Nitrogen N AND Group 17 - Halogens Cl AND Group 17 - Halogens F,Cl,Br,I,At by Chemical elements

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Group 15 - Phosphorus P OR Group 16 - Oxygen O OR Group 17 - Halogens Br OR Group 17 - Halogens I by Chemical elements

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Anilines (Unhindered) AND Inorganic Compound by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Vinyl/Allyl Nitriles by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "r"

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

Domain logical expression index: "s"

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

Domain logical expression index: "t"

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

Domain logical expression index: "u"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.226

Domain logical expression index: "v"

Parametric boundary:The target chemical should have a value of log Kow which is <= 4.13

Validity criteria fulfilled:

not specified

Conclusions:

The median Effective concentration (EC50) value for (4-(4-aminophenyl)(4-iminocyclohexa-2,5-dienylidene)methyl)-2-methylaniline hydrochloride on Daphnia magna in a 48 hour study was estimated to be 223 mg/L on the basis of effects on intoxication

Executive summary:

Using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the five closest read across substances, the short term toxicity on aquatic invertebrates was predicted for target substance (4-(4-aminophenyl)(4-iminocyclohexa-2,5-dienylidene)methyl)-2-methylaniline hydrochloride (CAS no. 632 -99 -5). EC50 value was estimated to be 223 mg/l for Daphnia magna for 48 h duration. Based on this value it can be concluded that the substance (4 -(4 -aminophenyl)(4 -iminocyclo hexa-2,5 -dienylidene)methyl)-2 -methylaniline hydrochloride is considered to be non-toxic to aquatic environment and can be considered to be not classified as per the CLP classification criteria.

Description of key information

Using the OECD QSAR toolbox version 3.3 (2017) with log kow as the primary descriptor and considering the five closest read across substances, the short term toxicity on aquatic invertebrates was predicted for target substance (4-(4-aminophenyl)(4-iminocyclohexa-2,5-dienylidene)methyl)-2-methylaniline hydrochloride (CAS no. 632 -99 -5). EC50 value was estimated to be 223 mg/l for Daphnia magna for 48 h duration. Based on this value it can be concluded that the substance (4 -(4 -aminophenyl)(4 -iminocyclo hexa-2,5 -dienylidene)methyl)-2 -methylaniline hydrochloride is considered to be non-toxic to aquatic environment and can be considered to be not classified as per the CLP classification criteria.

Key value for chemical safety assessment

EC50/LC50 for freshwater invertebrates:

223 mg/L

Additional information

Various predicted data for the target chemical (4-(4-aminophenyl)(4-iminocyclohexa-2,5-dienylidene)methyl)-2-methylaniline hydrochloride (CAS No. 632-99-5) and various supporting weight of evidence studies for its closest read across substances with logKow as the primary descriptorwere reviewed to summarize the following information:

 

Short term toxicity on aquatic invertebrate of target chemical(4-(4-aminophenyl)(4-iminocyclohexa-2,5-dienylidene)methyl)-2-methylaniline hydrochloride (CAS No. 632-99-5) is predicted using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the five closest read across substances (2017). On the basis of effects observed in a static freshwater system, the effect concentration EC50 value for the substance is estimated to be 233 mg/l for Daphnia magna for 48 hr duration.Based on this value it can be concluded that the substance (4 -(4 -aminophenyl)(4 -iminocyclo hexa-2,5 -dienylidene)methyl)-2 -methylaniline hydrochloride is considered to be non-toxic to aquatic environment and can be considered to be not classified as per the CLP classification criteria.

 

In another prediction done using the EPI Suite ECOSAR version 1.10 (EPI Suite, 2017), the short term toxicity on aquatic invertebrates was predicted for test substance(4-(4-aminophenyl)(4-iminocyclohexa-2,5-dienylidene)methyl)-2-methylaniline hydrochloride (CAS No. 632-99-5).On the basis of effects observed in a static freshwater system, the effect concentration EC50 value for the substance is estimated to be 1186.437 mg/l for Daphnia magna for 48 h duration.Based on this value it can be concluded that the substance (4-(4-aminophenyl)(4-iminocyclohexa-2,5-dienylidene)methyl)-2-methylaniline hydrochloride is considered to be not toxic to aquatic environment and can be not classified as per the criteria mentioned in CLP regulation.

 

In a weight of evidencestudy from authoritative database (ECOTOX database, 2017) of the read across chemical 4-[(4-dimethylaminophenyl)-phenylmethylidene]cyclohexa-2,5-dien-1-ylidene]-dimethylazanium chloride (CAS no. 569-64-2),Short term toxicity to Litopenaeus schmitti (Southern white shrimp) study was carried out 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 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), respectively. 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.

 

Another short term toxicity to Daphnia magna (Water flea) studyof the read across chemical 1-Hexene (CAS no. 592-41-6)was carried out for 48 hrs(ECOTOX database, 2017). The study was based on the effects of the read across compound 1-Hexene on Daphnia magna in a static fresh water system at a temperature of 20⁰C, hardness of water was approx. 210 mg/l CaCO3, dissolved oxygen ≥ 70%and pH range of 8.0 to 8.2, respectively. Daphnia magna (Water flea) of < 24 h old was used as a test organism. Study was performed using synthetic medium in glass stopped conical flask. Based on effect on intoxication of the test organism Daphnia magna, the 48 hr EC50 value was determined to be 30 mg/l. Thus, based on the EC50 value, it can be concluded that the substance 1-Hexenecan be considered as toxic to aquatic organisms. Since the test chemical 1-Hexene is readily biodegradable in nature, chemical 1-Hexene can be considered as non-toxic to aquatic organism and thus cannot be classified as hazardous as per the CLP classification criteria.

 

For the same read across chemical 1-Hexene(CAS no. 592-41-6) from authoritative database (ECOTOX database, 2017), short term toxicity to Daphnia magna (Water flea) study was carried out for 48 hrs. The study was based on the effects of the test compound1-Hexene(CAS no. 592-41-6) on Daphnia magna in a static fresh water system at a temperature of 20⁰C, hardness of water was approx. 210 mg/l CaCO3, dissolved oxygen ≥ 70% and pH range of 8.0 to 8.2, respectively. Daphnia magna (Water flea) of< 24 h old was used as a test organism. Study was performed using synthetic medium in glass beaker covered with a watch glass. Based on effect on intoxication of the test organism Daphnia magna, the 48 hr EC50 value was determined to be 60 mg/l (EC50 value ranges from > 32 to < 100 mg/l, respectively).Thus, based on the EC50 value, it can be concluded that the substance 1-Hexene can be considered as toxic to aquatic organisms. Since the test chemical 1-Hexene is readily biodegradable in nature, chemical 1-Hexene can be considered as non-toxic to aquatic organism and thus cannot be classified as hazardous as per the CLP classification criteria.

 

In a supporting weight of evidence study from secondary source (OECD SIDS, 2001), short term toxicity to Daphnia magna (Water flea) study was carried out for 48 hrs. The study was based on the effects of the read compound 1-Hexene (CAS no. 592-41-6) on Daphnia magna in a static fresh water system. The 24 and 48 hrs EC50 value was determined to be 540 and 230 mg/l, respectively. Thus, based on the EC50 value, it can be concluded that the substance 1-Hexene can be considered as non-toxic to aquatic organism and thus cannot be classified as hazardous as per the CLP classification criteria.

 

Thus, based on the overall reported results for target chemical(4-(4-aminophenyl)(4-iminocyclohexa-2,5-dienylidene)methyl)-2-methylaniline hydrochloride(OECD QSAR toolbox version 3.3 and EPI suite, 2017) and for its read across substance (fromauthoritative database ECOTOX and secondary source OECD SIDS),it can be concluded that the test substance (4-(4-aminophenyl)(4-iminocyclohexa-2,5-dienylidene)methyl)-2-methylaniline hydrochloride can be considered as non-toxic to aquatic environment and can be considered to be not classified as per the CLP classification criteria.