2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride

Toxicity to aquatic algae and cyanobacteria

Link to relevant study record(s)

Reference

Endpoint:

toxicity to aquatic algae and cyanobacteria

Type of information:

(Q)SAR

Adequacy of study:

key study

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

Guideline:

other: as mentioned below

Principles of method if other than guideline:

Prediction is done using OECD QSAR Toolbox version 3.4 with logKow as the primary descriptor.

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material : 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride
- Molecular formula : C24H30Cl2N2
- Molecular weight : 417.421 g/mol
- Smiles notation : C1(=[N+](c2ccccc2C1(C)C)C)\C=C/c1c(cc(N(CCCl)CC)cc1)C.[ClH-]
- InChl : 1S/C24H30ClN2.ClH/c1-6-27(16-15-25)20-13-11-19(18(2)17-20)12-14-23-24(3,4)21-9-7-8-10-22(21)26(23)5;/h7-14,17H,6,15-16H2,1-5H3;1H/q+1;/p-1
- Substance type: Organic
- Physical state: Solid

Analytical monitoring:

not specified

Vehicle:

not specified

Test organisms (species):

Desmodesmus subspicatus (previous name: Scenedesmus subspicatus)

Test type:

static

Water media type:

freshwater

Total exposure duration:

72 h

Test temperature:

21 °C

pH:

5.3 - 7.3

Reference substance (positive control):

not specified

Key result

Duration:

72 h

Dose descriptor:

EC50

Effect conc.:

11.592 mg/L

Nominal / measured:

estimated

Conc. based on:

test mat.

Basis for effect:

growth rate

The prediction was based on dataset comprised from the following descriptors: EC50
Estimation method: Takes average value from the 5 nearest neighbours
Domain  logical expression:Result: In Domain

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

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Radical OR Radical >> Generation of ROS by glutathione depletion (indirect) OR Radical >> Generation of ROS by glutathione depletion (indirect) >> Haloalkanes Containing Heteroatom OR SN2 OR SN2 >> Alkylation, direct acting epoxides and related after cyclization OR SN2 >> Alkylation, direct acting epoxides and related after cyclization >> Nitrogen and Sulfur Mustards OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom >> Haloalkanes Containing Heteroatom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Haloalkanes Containing Heteroatom by DNA binding by OASIS v.1.4 ONLY

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as SN1 OR SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine OR SN2 OR SN2 >> Episulfonium Ion Formation OR SN2 >> Episulfonium Ion Formation >> Mustards by DNA binding by OECD ONLY

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as SN2 OR SN2 >> Nucleophilic substitution at sp3 carbon atom OR SN2 >> Nucleophilic substitution at sp3 carbon atom >> Alkyl halides  OR SN2 >> Ring opening SN2 reaction OR SN2 >> Ring opening SN2 reaction >> Mustard compounds  by Protein binding by OASIS v1.4 ONLY

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as SN1 AND SN1 >> Nitrenium Ion formation AND SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine AND SN2 AND SN2 >> Episulfonium Ion Formation AND SN2 >> Episulfonium Ion Formation >> Mustards by DNA binding by OECD

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as SN2 >> SN2 at an sp3 Carbon atom OR SN2 >> SN2 at an sp3 Carbon atom >> Aliphatic halides by DNA binding by OECD

Domain logical expression index: "f"

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

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Weak binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Class 5 (Not possible to classify according to these rules) by Acute aquatic toxicity classification by Verhaar (Modified) ONLY

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Reactive unspecified by Acute aquatic toxicity MOA by OASIS ONLY

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Reactive unspecified by Acute aquatic toxicity MOA by OASIS ONLY

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Alkene AND Alkyl arenes AND Alkyl halide AND Ammonium salt AND Aromatic amine AND Aryl AND Indole/ Isoindole by Organic Functional groups

Domain logical expression index: "l"

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

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Alkene AND Alkyl arenes AND Alkyl halide AND Ammonium salt AND Aromatic amine AND Aryl AND Indole/ Isoindole by Organic Functional groups

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Aromatic heterocyclic halide by Organic Functional groups

Domain logical expression index: "o"

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: "p"

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

Domain logical expression index: "q"

Parametric boundary:The target chemical should have a value of log Kow which is >= -1.36

Domain logical expression index: "r"

Parametric boundary:The target chemical should have a value of log Kow which is <= 9.29

Validity criteria fulfilled:

not specified

Conclusions:

The median Effective concentration (EC50) value for 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3- trimethyl-3H-indolium chloride on Desmodesmus subspicatus in a 72 hour study was estimated to be 11.6 mg/L on the basis of effects on growth rate.

Executive summary:

Using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the five closest read across substances, the short term toxicity on aquatic algae and cyanobacteria was predicted for target substance 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3- trimethyl-3H-indolium chloride (CAS no. 6441 -82 -3). EC50 value was estimated to be 11.6 mg/l for Desmodesmus subspicatus for 72 h duration. Based on this value it can be concluded that the substance 2 -[2 -[4 -[(2 -chloroethyl)ethylamino] -o-tolyl]vinyl]-1,3,3 - trimethyl-3H-indolium chloride is considered to be toxic to aquatic environment and can be considered to be classified in aquatic chronic category 3 as per the CLP classification criteria.

Description of key information

Using the OECD QSAR toolbox version 3.4 (2018) with log kow as the primary descriptor and considering the five closest read across substances, the short term toxicity on aquatic algae and cyanobacteria was predicted for target substance 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3- trimethyl-3H-indolium chloride (CAS no. 6441 -82 -3). EC50 value was estimated to be 11.6 mg/l for Desmodesmus subspicatus for 72 h duration. Based on this value it can be concluded that the substance 2 -[2 -[4 -[(2 -chloroethyl)ethylamino] -o-tolyl]vinyl]-1,3,3 - trimethyl-3H-indolium chloride is considered to be toxic to aquatic environment and can be considered to be classified in aquatic chronic category 3 as per the CLP classification criteria.

Key value for chemical safety assessment

EC50 for freshwater algae:

11.6 mg/L

Additional information

Predicted data for the target chemical 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3- trimethyl-3H-indolium chloride (CAS No. 6441-82-3) and supporting weight of evidence study for its closest read across substances with logKow as the primary descriptorwere reviewed for toxicity to aquatic algae and cyanobacteria endpoint to summarize the following information:

 

Short term toxicity on aquatic algae and cyanobacteria of target chemical 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3- trimethyl-3H-indolium chloride (CAS No. 6441-82-3) is predicted using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the five closest read across substances (2018).On the basis of effects observed in a static freshwater system, the effect concentration EC50 value for the substance is estimated to be 11.6 mg/l for Desmodesmus subspicatus for 72 duration.

 

In a supporting weight of evidence study from authoritative database (J-CHECK, 2017) of the read across chemical disodium 4,4'-bis[(4 -anilino-6 -morpholino-1,3,5 -triazin-2 -yl)amino]stilbene-2,2'-disulphonate (CAS no. 16090-02-1),short term toxicity to green algae study was carried out for 72 hrs. The study was based on the effects of the read across compound disodium 4,4'-bis[(4 -anilino-6 -morpholino-1,3,5 -triazin-2 -yl)amino]stilbene-2,2'-disulphonate (CAS no. 16090 -02 -1) on green algae in a static fresh water system. Based on effect on growth rate of the test organism green algae, the 72 hr EC50 and NOEC value was determined to be > 65 and 6.3 mg/l, respectively and on the basis of AUG, the 72 hr EC50 and NOEC value was determined to be 20 and 3.3 mg/l, respectively.

 

Thus, based on the overall reported results for target chemical 2 -[2 -[4 -[(2 -chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3 - trimethyl-3H-indolium chloride (OECD QSAR toolbox version 3.4, 2017) and for its read across substance (from authoritative database J-CHECK),it can be concluded that the test substance 2 -[2 -[4 -[(2 -chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3 - trimethyl-3H-indolium chloride can be considered as toxic to aquatic algae and cyanobacteria and can be considered to be classifiedin aquatic chronic category 3 as per the CLP classification criteria.