N-(4-chlorobenzhydryl)piperazine

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:

Data is from OECD QSAR toolbox version.3.3 and QMRF report has been attached.

Qualifier:

according to guideline

Guideline:

other: Predicted data

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.3 with log kow as the primary discriptors.

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of the test material: 1-[(4-chlorophenyl)(phenyl)methyl]piperazine
- Common Name: Norchlorcyclizine
- IUPAC name: 1-[(4-chlorophenyl)(phenyl)methyl]piperazine
- Molecular weight: 286.804 g/mol
- Molecular formula: C17H19ClN2
- Substance type: Organic
- SMILES Notation: c1([C@@H](c2ccccc2)N2CCNCC2)ccc(Cl)cc1
- InChI: 1S/C17H19ClN2/c18-16-8-6-15(7-9-16)17(14-4-2-1-3-5-14)20-12-10-19-11-13-20/h1-9,17,19H,10-13H2
- Physical State: Solid (white to pale yellow)

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.:

112.764 mg/L

Nominal / measured:

estimated

Conc. based on:

test mat.

Basis for effect:

growth rate

Remarks on result:

other: not toxic

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" or "d" or "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" )  and ("p" and ( not "q") )  )  and ("r" and "s" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Secondary amines by OECD HPV Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Aliphatic Amines by US-EPA New Chemical Categories

Domain logical expression index: "c"

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 by DNA binding by OECD

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Narcotic Amine by Acute aquatic toxicity MOA by OASIS

Domain logical expression index: "e"

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

Domain logical expression index: "f"

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

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Carbamoylation after isocyanate formation OR AN2 >> Carbamoylation after isocyanate formation >> N-Hydroxylamines OR AN2 >> Shiff base formation after aldehyde release OR AN2 >> Shiff base formation after aldehyde release >> Specific Acetate Esters OR Radical OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> N-Hydroxylamines OR SN1 OR SN1 >> Carbenium ion formation OR SN1 >> Carbenium ion formation >> Alpha-Haloethers OR SN1 >> Nucleophilic attack after carbenium ion formation OR SN1 >> Nucleophilic attack after carbenium ion formation >> Specific Acetate Esters OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> N-Hydroxylamines OR SN2 OR SN2 >> Acylation OR SN2 >> Acylation >> Specific Acetate Esters OR SN2 >> Alkylation, direct acting epoxides and related OR SN2 >> Alkylation, direct acting epoxides and related >> Epoxides and Aziridines OR SN2 >> Direct acting epoxides formed after metabolic activation OR SN2 >> Direct acting epoxides formed after metabolic activation >> Quinoline Derivatives OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Specific Acetate Esters OR SN2 >> SN2 at an activated carbon atom OR SN2 >> SN2 at an activated carbon atom >> Quinoline Derivatives OR SN2 >> SN2 at sp3-carbon atom OR SN2 >> SN2 at sp3-carbon atom >> Alpha-Haloethers by DNA binding by OASIS v.1.3

Domain logical expression index: "h"

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

Domain logical expression index: "i"

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: "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 >> Direct acylation involving a leaving group OR Acylation >> Direct acylation involving a leaving group >> Carbamates  OR Acylation >> Ester aminolysis OR Acylation >> Ester aminolysis >> Amides OR Schiff base formation OR Schiff base formation >> Schiff base formation with carbonyl compounds OR Schiff base formation >> Schiff base formation with carbonyl compounds >> Aldehydes by Protein binding by OASIS v1.3

Domain logical expression index: "l"

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

Domain logical expression index: "m"

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 by Protein binding by OECD

Domain logical expression index: "n"

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: "o"

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

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Inclusion rules not met by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Primary and secondary aliphatic amines by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "r"

Parametric boundary:The target chemical should have a value of log Kow which is >= -0.386

Domain logical expression index: "s"

Parametric boundary:The target chemical should have a value of log Kow which is <= 5.72

Conclusions:

Based on the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the closest read across substances, the toxicity to aquatic algae was predicted 1-[(4-chlorophenyl)(phenyl)methyl]piperazine (CAS: 303-26-4). EC50 growth rate value was estimated to be 112.764 mg/l for Pseudokirchneriella subcapitata for 72 hrs duration. It was concluded that 1-[(4-chlorophenyl)(phenyl)methyl]piperazine (CAS: 303-26-4) was likely to be not toxic to aquatic algae.

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 closest read across substances, the toxicity to aquatic algae was predicted 1-[(4-chlorophenyl)(phenyl)methyl]piperazine (CAS: 303-26-4). EC50 growth rate value was estimated to be 112.764 mg/l for Pseudokirchneriella subcapitata for 72 hrs duration. It was concluded that 1-[(4-chlorophenyl)(phenyl)methyl]piperazine (CAS: 303-26-4) was likely to be not toxic to aquatic algae.

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 closest read across substances, the toxicity to aquatic algae was predicted 1-[(4-chlorophenyl)(phenyl)methyl]piperazine (CAS: 303-26-4). EC50 growth rate value was estimated to be 112.764 mg/l for Pseudokirchneriella subcapitata for 72 hrs duration. It was concluded that 1-[(4-chlorophenyl)(phenyl)methyl]piperazine (CAS: 303-26-4) was likely to be not toxic to aquatic algae.

Key value for chemical safety assessment

EC50 for freshwater algae:

112.764 mg/L

Additional information

Following studies of target chemical and structurally similar read across includes predicted data and experimental data to conclude the toxicity extent of 1-[(4-chlorophenyl)(phenyl)methyl]piperazine (CAS: 303-26-4) towards aquatic algae is summarized as follows:

Based on the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the closest read across substances, the toxicity to aquatic algae was predicted 1-[(4-chlorophenyl)(phenyl)methyl]piperazine (CAS: 303-26-4). EC50 growth rate value was estimated to be 112.764 mg/l for Pseudokirchneriella subcapitata for 72 hrs duration. It was concluded that 1-[(4-chlorophenyl)(phenyl)methyl]piperazine (CAS: 303-26-4) was likely to be not toxic to aquatic algae.

The above predicted data of target chemical is supported by the experimental study of structurally similar read across piperazine (CAS: 110-85-0) from the J-CHeck, suggests that the Short term toxicity to algae study was carried out for 72 hrs. The study was performed according to OECD Guideline 201 (Alga, Growth Inhibition Test). On the basis of growth rate and AUG of the test organism algae,the 72 hrs EC50 values was determined to be 130 and 91 mg/l, respectively and NOEC values was determined to be 34 and 46 mg/l, respectively.Thus, based on the EC50 value (91 mg/l), it can be concluded that the piperazine (CAS: 110-85-0) can be considered as toxic to aquatic organisms and thus can be classified as aquatic chronic category 3 but since the read across substance is readily biodegradable, it can be considered as non-hazardous to aquatic organisms as per the CLP criteria.

Thus based on the effect concentrations which is in the range 110 mg/l to 116.794 mg/l give the conclusion that test substance 1-[(4-chlorophenyl)(phenyl)methyl]piperazine (CAS: 303-26-4) was likely to be not toxic to aquatic algae at environmentally relevant concentrations and can be considered to be “not classified” as per the CLP classification criteria.