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

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 201 (Alga, Growth Inhibition Test)

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):

Raphidocelis subcapitata (previous names: Pseudokirchneriella subcapitata, Selenastrum capricornutum)

Test type:

static

Water media type:

freshwater

Total exposure duration:

72 h

Key result

Duration:

72 h

Dose descriptor:

EC50

Effect conc.:

156.792 mg/L

Nominal / measured:

estimated

Conc. based on:

test mat.

Basis for effect:

growth rate

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 6 nearest neighbours
Domain  logical expression:Result: In Domain

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

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 Michael addition AND Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals AND Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Arenes AND SN1 AND SN1 >> Iminium Ion Formation AND SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines AND SN1 >> Nitrenium Ion formation AND SN1 >> Nitrenium Ion formation >> Aromatic azo AND SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine AND SN1 >> Nitrenium Ion formation >> Unsaturated heterocyclic azo by DNA binding by OECD ONLY

Domain logical expression index: "e"

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

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Non binder, impaired OH or NH2 group OR Non binder, MW>500 OR Non binder, non cyclic structure by Estrogen Receptor Binding

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as No alert found by Carcinogenicity (genotox and nongenotox) alerts by ISS

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Alkyl carbamate and thiocarbamate (Genotox) OR Aromatic mono-and dialkylamine (Genotox) OR Structural alert for genotoxic carcinogenicity OR Structural alert for nongenotoxic carcinogenicity OR Thiocarbonyl (Nongenotox) by Carcinogenicity (genotox and nongenotox) alerts by ISS

Domain logical expression index: "i"

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

Domain logical expression index: "j"

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

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Ester aminolysis OR Acylation >> Ester aminolysis >> Amides OR Acylation >> Ring opening acylation OR Acylation >> Ring opening acylation >> beta-Lactams  by Protein binding by OASIS v1.3

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as No superfragment by Superfragments ONLY

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Amidine AND Ammonium salt AND Aromatic amine AND Aryl AND Azo AND Benzyl AND Unsaturated heterocyclic amine AND Unsaturated heterocyclic fragment by Organic Functional groups

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Alkyl arenes OR Alkyne by Organic Functional groups

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Amidine AND Ammonium salt AND Aromatic amine AND Aryl AND Azo AND Benzyl AND Unsaturated heterocyclic amine AND Unsaturated heterocyclic fragment by Organic Functional groups

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Alkane, branched with tertiary carbon by Organic Functional groups

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Amidine AND Ammonium salt AND Aromatic amine AND Aryl AND Azo AND Benzyl AND Unsaturated heterocyclic amine AND Unsaturated heterocyclic fragment by Organic Functional groups

Domain logical expression index: "r"

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

Domain logical expression index: "s"

Parametric boundary:The target chemical should have a value of log Kow which is >= -0.382

Domain logical expression index: "t"

Parametric boundary:The target chemical should have a value of log Kow which is <= 1.99

Validity criteria fulfilled:

not specified

Conclusions:

When test chemical 5-[[p-(benzylmethylamino)phenyl]azo]-1,4-dimethyl-1H-1,2,4-triazolium chloride was exposed for 72 hrs on Pseudokirchneriella subcapitata (previous names: Raphidocelis subcapitata, Selenastrum capricornutum) alga, EC50 value was estimated to be 156.792 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:

Toxicity of test chemical 5-[[p-(benzylmethylamino)phenyl]azo]-1,4-dimethyl-1H-1,2,4-triazolium chloride (CAS no. 29508-47-2) 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 5-[[p-(benzylmethylamino)phenyl]azo]-1,4-dimethyl-1H-1,2,4-triazolium chloride was exposed for 72 hrs on Pseudokirchneriella subcapitata (previous names: Raphidocelis subcapitata, Selenastrum capricornutum) alga, EC50 value was estimated to be 156.792 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

Toxicity of test chemical 5-[[p-(benzylmethylamino)phenyl]azo]-1,4-dimethyl-1H-1,2,4-triazolium chloride (CAS no. 29508-47-2) 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 5-[[p-(benzylmethylamino)phenyl]azo]-1,4-dimethyl-1H-1,2,4-triazolium chloride was exposed for 72 hrs on Pseudokirchneriella subcapitata (previous names: Raphidocelis subcapitata, Selenastrum capricornutum) alga, EC50 value was estimated to be 156.792 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 for freshwater algae:

156.792 mg/L

Additional information

Results of predicted data study for target chemical 5-[[p-(benzylmethylamino)phenyl]azo]-1,4-dimethyl-1H-1,2,4-triazolium chloride (CAS no. 29508-47-2) and experimental studies for read across chemical have been conducted to determine toxicity to aquatic algae and cyanobacteria endpoint are summarized below.

In first weight of evidence study the toxicity of test chemical 5-[[p-(benzylmethylamino)phenyl]azo]-1,4-dimethyl-1H-1,2,4-triazolium chloride (CAS no. 29508-47-2) 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 5-[[p-(benzylmethylamino)phenyl]azo]-1,4-dimethyl-1H-1,2,4-triazolium chloride was exposed for 72 hrs on Pseudokirchneriella subcapitata (previous names: Raphidocelis subcapitata, Selenastrum capricornutum) alga, EC50 value was estimated to be 156.792 mg/L.

Another weight of evidence study was done by using authoritative database HSDB (2017) for read across chemical in this study the toxicity of read across chemical Benzenemethanol on Haematococcus pluvialis algae was determined on the basis of inhibition of Photosynthesis for 24 hrs. EC50 value was determined to be 2600 mg/L when read across chemical benzenemethanol was exposed to Haematococcus pluvialis (Algae) for 24 hrs.

Next weight of evidence study was done from same source and for same read across chemical as mentioned above (HSDB, 2017) in this study the toxicity of read across chemical Benzenemethanol on Anabaena inaequalis algae was determined on the basis of effect on population (decreased Photosynthesis) for 3 hrs. EC50 value was determined to be greater than 100 mg/L on the basis of effect on population (decreased photosysnthesis ) when read across chemical benzenemethanol was exposed to Anabaena inaequalis (Blue-Green Algae) for 3 hrs.

Last weight of evidence study was done from authoritative database (J Check, 2017) for same read across chemical as mentioned in above both the studies. This study was conducted to determine the toxic nature of read across chemical chemical Benzyl alcohol on the growth of aquatic green algae. Test was performed according to the OECD Guideline 201 (Alga, Growth Inhibition Test). Green algae exposed for 72hrs with the chemical. Test conducted by the static system. After the exposure of chemical, the effect concentration and no observed effect concentration was measured. Based on the growth rate inhibition of green algae the EC50 and NOEC was 770 mg/l and 310 mg/l. Based on the Area under the growth curved (AUG), the EC50 and NOEC was 500 and 310 mg/l by the exposure of chemical Benzyl alcohol for 72hrs. Thus it was concluded that the chemical was nontoxic and can be consider to be not classified as per the CLP classification criteria.

Thus based on the effect concentrations it is concluded 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 not 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.