5-[[p-(benzylmethylamino)phenyl]azo]-1,4-dimethyl-1H-1,2,4-triazolium 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:

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

Specific details on test material used for the study:

- Name of the test material: 5-[[p-(benzylmethylamino)phenyl]azo]-1,4-dimethyl-1H-1,2,4-triazolium chloride
- IUPAC name: 5-[[p-(benzylmethylamino)phenyl]azo]-1,4-dimethyl-1H-1,2,4-triazolium chloride
- Molecular formula: C18H21N6Cl
- Molecular weight: 356.8589 g/mol
- Substance type: Organic
- Smiles: Cc1cn[n+](n1/N=N/c2ccc(cc2)N(C)Cc3ccccc3)C.[Cl-]
- Inchi: 1S/C18H21N6.ClH/c1-15-13-19-23(3)24(15)21-20-17-9-11-18(12-10-17)22(2)14-16-7-5-4-6-8-16;/h4-13H,14H2,1-3H3;1H/q+1;/p-1/b21-20+;

Analytical monitoring:

not specified

Vehicle:

not specified

Test organisms (species):

Daphnia magna

Test type:

static

Water media type:

freshwater

Total exposure duration:

48 h

Key result

Duration:

48 h

Dose descriptor:

EC50

Effect conc.:

154.304 mg/L

Nominal / measured:

estimated

Conc. based on:

test mat.

Basis for effect:

other: Intoxication

Remarks on result:

other: not classified

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" )  and "c" )  and ("d" and ( not "e") )  )  and ("f" and ( not "g") )  )  and "h" )  and ("i" and ( not "j") )  )  and ("k" and ( not "l") )  )  and "m" )  and "n" )  and ("o" and "p" )  )

Domain logical expression index: "a"

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 SN1 OR SN1 >> Iminium Ion Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines OR SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >> Aromatic azo OR SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine OR SN1 >> Nitrenium Ion formation >> Unsaturated heterocyclic azo by DNA binding by OECD ONLY

Domain logical expression index: "b"

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

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.3 ONLY

Domain logical expression index: "d"

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

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Direct acylation involving a leaving group OR Acylation >> Direct acylation involving a leaving group >> (Thio)Acetates  OR Acylation >> Direct acylation involving a leaving group >> Azlactones and unsaturated lactone derivatives  OR Acylation >> Direct acylation involving a leaving group >> Carbamates  OR Acylation >> Direct acylation involving a leaving group >> N-Acylated heteroaromatic amines  OR Acylation >> Direct acylation involving a leaving group >> N-Acylsulfonamides  OR Acylation >> Ester aminolysis OR Acylation >> Ester aminolysis >> Amides OR Acylation >> Ester aminolysis >> Dithiocarbamates OR Acylation >> Ring opening acylation OR Acylation >> Ring opening acylation >> beta-Lactams  OR Ionic interaction OR Ionic interaction >> Substituted guanidines OR Ionic interaction >> Substituted guanidines >> Guanidines 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 Michael Addition >> Quinone type chemicals OR Michael Addition >> Quinone type chemicals >> Pyranones, Pyridones (and related nitrogen chemicals)  OR Nucleophilic addition OR Nucleophilic addition >> Addition to carbon-hetero double bonds OR Nucleophilic addition >> Addition to carbon-hetero double bonds >> Ketones OR Schiff base formation OR Schiff base formation >> Direct acting Schiff base formers OR Schiff base formation >> Direct acting Schiff base formers >> 1,2-Dicarbonyls and 1,3-Dicarbonyls  OR Schiff base formation >> Pyrazolones and Pyrazolidinones derivatives OR Schiff base formation >> Pyrazolones and Pyrazolidinones derivatives >> Pyrazolones and Pyrazolidinones  OR Schiff base formation >> Schiff base formation with carbonyl compounds OR Schiff base formation >> Schiff base formation with carbonyl compounds >> Aldehydes 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 >> alpha-Activated haloalkanes  OR SN2 >> Nucleophilic substitution on benzilyc carbon atom OR SN2 >> Nucleophilic substitution on benzilyc carbon atom >> alpha-Activated benzyls  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 OR SNVinyl OR SNVinyl >> SNVinyl at a vinylic (sp2) carbon atom OR SNVinyl >> SNVinyl at a vinylic (sp2) carbon atom >> Vinyl type compounds with electron withdrawing groups  by Protein binding by OASIS v1.3

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as No alert found by Protein binding by OECD

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Direct Acylation Involving a Leaving group OR Acylation >> Direct Acylation Involving a Leaving group >> Acetates OR Michael addition OR Michael addition >> Quinones and Quinone-type Chemicals OR Michael addition >> Quinones and Quinone-type Chemicals >> Pyranones (and related nitrogen chemicals) OR SN2 OR SN2 >> SN2 reaction at a sp2 carbon atom OR SN2 >> SN2 reaction at a sp2 carbon atom >> Polarised alkenes with a halogen leaving group OR SN2 >> SN2 reaction at sp3 carbon atom OR SN2 >> SN2 reaction at sp3 carbon atom >> Allyl acetates and related chemicals by Protein binding by OECD

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Class 3 (unspecific reactivity) by Acute aquatic toxicity classification by Verhaar (Modified) ONLY

Domain logical expression index: "i"

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

Domain logical expression index: "j"

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

Domain logical expression index: "k"

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

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Phenol Amines OR Phenols OR Pyrazoles/Pyrroles OR Substituted Ureas OR Triazines, Aromatic OR Triazoles (Non-Fused) OR Vinyl/Allyl Ethers by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "m"

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

Domain logical expression index: "n"

Similarity boundary:Target: CN{+}1(.Cl{-})C(N=Nc2ccc(N(C)Cc3ccccc3)cc2)N(C)C=N1
Threshold=30%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "o"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.559

Domain logical expression index: "p"

Parametric boundary:The target chemical should have a value of log Kow which is <= 1.08

Validity criteria fulfilled:

not specified

Conclusions:

The EC50 value was estimated to be 154.304 mg/L when test chemical 5-[[p-(benzylmethylamino)phenyl]azo]-1,4-dimethyl-1H-1,2,4-triazolium chloride was exposed to daphnia magna for 48 hrs

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 five closest read across substances, toxicity on daphnia magna predicted for test chemical 5-[[p-(benzylmethylamino)phenyl]azo]-1,4-dimethyl-1H-1,2,4-triazolium chloride (CAS no.29508-47-2). The EC50 value was estimated to be 154.304 mg/L when test chemical5-[[p-(benzylmethylamino)phenyl]azo]-1,4-dimethyl-1H-1,2,4-triazolium chloride was exposed to daphnia magna for 48 hrs. On the basis of EC 50 value it is concluded that this test chemical in non toxic to aquatic invertebrates and considered as not classified as per CLP regulation.

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 five closest read across substances, toxicity on daphnia magna predicted for test chemical 5-[[p-(benzylmethylamino)phenyl]azo]-1,4-dimethyl-1H-1,2,4-triazolium chloride (CAS no.29508-47-2). The EC50 value was estimated to be 154.304 mg/L when test chemical5-[[p-(benzylmethylamino)phenyl]azo]-1,4-dimethyl-1H-1,2,4-triazolium chloride was exposed to daphnia magna for 48 hrs. On the basis of EC 50 value it is concluded that this test chemical in non toxic to aquatic invertebrates and considered as not classified as per CLP regulation.

Key value for chemical safety assessment

Fresh water invertebrates

Fresh water invertebrates

Effect concentration:

154.304 mg/L

Additional information

Following studies include the predicted data study for the target chemical and experimental studies for read across chemicals with log Kow as primary descriptor to conclude the toxicity extent of 5-[[p-(benzylmethylamino)phenyl]azo]-1,4-dimethyl-1H-1,2,4-triazolium chloride (CAS no.29508-47-2)towards aquatic invertebrate are summarized as follows:

First weight of study was based on the prediction done by using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the five closest read across substances, toxicity on daphnia magna predicted for test chemical 5-[[p-(benzylmethylamino)phenyl]azo]-1,4-dimethyl-1H-1,2,4-triazolium chloride (CAS no. 29508-47-2). The EC50 value was estimated to be 154.304 mg/L when test chemical 5-[[p-(benzylmethylamino)phenyl]azo]-1,4-dimethyl-1H-1,2,4-triazolium chloride was exposed to daphnia magna for 48 hrs.

Another weight of evidence study was experimental study done from Environment International vol. 33 (2007) pg 370–375 in this study short term toxicity to daphnia magna was determined by using test guideline as mentioned in USEPA 2002. The culture water used in test was moderately hard water and daphnia magna were kept in 6L glass jar, fed daily on YTC and photoperiod applied during test was 16L:8D . Temperature during the test was maintained at 20 oC. The EC50 value of read across chemical (Z)-2-cyano-1-methyl-3-(2-{[(5-methyl-1H-imidazol-4-yl)methyl]sulfanyl}ethyl)guanidine was determined to be 379.7 in 48 hrs and 271.3 in 96 hrs in daphnia magna. On the basis of these EC 50 values it is concluded that this read across chemical is non toxic to aquatic invertebrate and can be considered in not classified category as per the CLP regulation.

Last weight of evidence stud was done from Ecotox database (2017) in this study the Short term toxicity to aquatic invertebrate Daphnia Magna was determined by exposing it to read across chemical (E)-1-(6-Chloro-3-pyridinylmethyl)-N-nitroimidazolidin-2- ylideneamine (CAS no. 138261-41-3). ET 50 value was determined to be 158 mg/L at 20 oC. Since ET 50 value is greater than 100 mg/L  read across chemical (E)-1-(6-Chloro-3-pyridinylmethyl)-N-nitroimidazolidin-2- ylideneamine is considered as not classified according to CLP classification criteria.

Thus based on the effect concentrations which is in the range 154.304 – 271.3 mg/L give the conclusion that test substance 5-[[p-(benzylmethylamino)phenyl]azo]-1,4-dimethyl-1H-1,2,4-triazolium chloride (CAS no.29508-47-2) was likely to be toxic to aquatic invertebrate at environmentally relevant concentrations and applying weight of evidence approach it can be considered to be “not Classified” as per the CLP classification criteria.