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

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

Guideline:

OECD Guideline 202 (Daphnia sp. Acute Immobilisation Test)

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):

Daphnia magna

Test type:

static

Water media type:

freshwater

Total exposure duration:

48 h

Hardness:

173 mg CaCO3/l

Test temperature:

22 °C

pH:

7.4-9.4

Dissolved oxygen:

6.5-9.1 mg/l

Reference substance (positive control):

not specified

Key result

Duration:

48 h

Dose descriptor:

EC50

Effect conc.:

10.451 mg/L

Nominal / measured:

estimated

Conc. based on:

test mat.

Basis for effect:

mobility

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 ( not "i") )  )  and ("j" and ( not "k") )  )  and ("l" and ( not "m") )  )  and ("n" and "o" )  )

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 Acylation OR Acylation >> P450 Mediated Activation to Acyl Halides OR Acylation >> P450 Mediated Activation to Acyl Halides >> 1,1-Dihaloalkanes OR 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 Not Related to an Existing ECOSAR Class by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "g"

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

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Not Related to an Existing ECOSAR Class by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "i"

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

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Not Related to an Existing ECOSAR Class by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "k"

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

Domain logical expression index: "l"

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 AND Overlapping groups by Organic Functional groups (nested)

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Alkoxy by Organic Functional groups (nested)

Domain logical expression index: "n"

Parametric boundary:The target chemical should have a value of log Kow which is >= 2.01

Domain logical expression index: "o"

Parametric boundary:The target chemical should have a value of log Kow which is <= 3.23

Validity criteria fulfilled:

not specified

Conclusions:

The median Effective concentration (EC50) value for chemical 2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium chloride on Daphnia magna in a 48 hour study was estimated to be 10.5 mg/L on the basis of effects on mobility.

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 invertebrates 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 10.5 mg/l for Daphnia magna for 48 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 invertebrates was predicted for target substance2-[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 10.5 mg/l for Daphnia magna for 48 h duration. Based on this value it can be concluded that the substance2-[2-[4-[(2-chloroethyl)ethylamino]-o-tolyl]vinyl]-1,3,3- trimethyl-3H-indolium chlorideis 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

Fresh water invertebrates

Fresh water invertebrates

Effect concentration:

10.5 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 various supporting weight of evidence studies for its read across substanceswere reviewed to summarize the following information:

 

Short term toxicity on aquatic invertebrate 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 10.5 mg/l for Daphnia magna for 48 hr duration.

 

In a supportingweight of evidence study from experimental study report (Sustainability Support Services (Europe) AB, Report no. 307/16, 2016) of the read across chemical Diethylaniline (CAS no. 91-66-7),experimental study for inhibition of the mobility of daphnids was carried out with the Diethylaniline (CAS no. 931 -66 -7) according to OECD Guideline 202. The animals used for the test shall be less than 24 h old and should not be of first brood progeny. The stock solution (100 mg/L) was prepared by dissolving clear yellow oily liquid in DMSO. The test solutions of required concentration as were prepared by mixing the stock solution of the test sample in reconstituted test water. The test substance was tested at the concentration of 0, 4, 10, 17, 30, 55 and 100 mg/L, respectively. The test was performed under static conditions in fresh water system at 20±1°C temperature. Effects on immobilisation were observed for 48 hours. EC50 was calculated using non-linear regression by the software Prism 4.0. The median effective concentration (EC50) for the test substance Diethylaniline (CAS no. 91 -66 -7) in Daphnia magna was determined to be 35.2 mg/L (95% CL: 24.8 -50.0 mg/l) for immobilisation effects.

 

Another short term toxicity to Daphnia magna (Water flea) study was carried out for 48 hrs (J-CHECK, 2017). The study was performed according to OECD Guideline 202 (Daphnia sp. Acute Immobilisation Test). The study was based on the effects of the read across compound Diethylaniline (CAS no. 91-66-7) on Daphnia magna in a static fresh water system. Daphnia magna (Water flea) was used as a test organism. Based on effect on mobility of the test organism Daphnia magna (Water flea), the 48 hr EC50 value was determined to be 11 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 experimental study report andauthoritative database J-CHECK),it can be concluded that the test substance 2 -[2 -[4 -[(2 -chloroethyl)ethyl amino]-o-tolyl]vinyl]-1,3,3 - trimethyl-3H-indolium chloride can be considered as toxic to aquatic invertebrates and can be considered to beclassified in aquatic chronic category 3 as per the CLP classification criteria.