Cinnamonitrile

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: as mentioned below

Principles of method if other than guideline:

Prediction was done by using OECD QSAR toolbox v3.3,2017

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material (IUPAC name): (E)-3-phenylprop-2-enenitrile
- Common name: Cinnamyl nitrile
- Molecular formula: C9H7N
- Molecular weight: 129.161 g/mol
- Smiles notation: N#C\C=C\c1ccccc1
- InChl: 1S/C9H7N/c10-8-4-7-9-5-2-1-3-6-9/h1-7H/b7-4+
- Substance type: Organic

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:

22.4 - 23.1°C

pH:

7.92 - 8.10

Duration:

72 h

Dose descriptor:

EC50

Effect conc.:

197.96 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" )  and ("e" and ( not "f") )  )  and ("g" and ( not "h") )  )  and ("i" and ( not "j") )  )  and ("k" and ( not "l") )  )  and "m" )  and "n" )  and ("o" and ( not "p") )  )  and ("q" and ( not "r") )  )  and ("s" and ( not "t") )  )  and ("u" and ( not "v") )  )  and ("w" and ( not "x") )  )  and ("y" and ( not "z") )  )  and ("aa" and ( not "ab") )  )  and ("ac" and ( not "ad") )  )  and ("ae" and ( not "af") )  )  and ("ag" and ( not "ah") )  )  and ("ai" and "aj" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Alkene AND Aryl AND Nitrile by Organic Functional groups

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Alkene AND Aryl AND Nitrile AND Overlapping groups by Organic Functional groups (nested)

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Acetylenic Carbon [#C] AND Aromatic Carbon [C] AND Olefinic carbon [=CH- or =C<] by Organic functional groups (US EPA)

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Aromatic compound by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "e"

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

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >>  Michael-type addition, quinoid structures OR AN2 >>  Michael-type addition, quinoid structures >> Quinoneimines OR AN2 >>  Michael-type addition, quinoid structures >> Quinones OR AN2 >> Nucleophilic addition to alpha, beta-unsaturated carbonyl compounds OR AN2 >> Nucleophilic addition to alpha, beta-unsaturated carbonyl compounds >> alpha, beta-Unsaturated Aldehydes OR AN2 >> Schiff base formation OR AN2 >> Schiff base formation >> alpha, beta-Unsaturated Aldehydes OR AN2 >> Schiff base formation by aldehyde formed after metabolic activation OR AN2 >> Schiff base formation by aldehyde formed after metabolic activation >> Geminal Polyhaloalkane Derivatives OR AN2 >> Shiff base formation for aldehydes OR AN2 >> Shiff base formation for aldehydes >> Geminal Polyhaloalkane Derivatives OR Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> Acridone, Thioxanthone, Xanthone and Phenazine Derivatives OR Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide Side Chain OR Non-covalent interaction >> DNA intercalation >> Fused-Ring Nitroaromatics OR Non-covalent interaction >> DNA intercalation >> Quinones OR Radical OR Radical >> Radical mechanism by ROS formation OR Radical >> Radical mechanism by ROS formation >> Acridone, Thioxanthone, Xanthone and Phenazine Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Fused-Ring Nitroaromatics OR Radical >> Radical mechanism via ROS formation (indirect) >> Geminal Polyhaloalkane Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitroaniline Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitroarenes with Other Active Groups OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR Radical >> Radical mechanism via ROS formation (indirect) >> Quinones OR Radical >> Radical mechanism via ROS formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines OR Radical >> ROS formation after GSH depletion (indirect) OR Radical >> ROS formation after GSH depletion (indirect) >> Quinoneimines OR SN1 OR SN1 >> Carbenium ion formation OR SN1 >> Carbenium ion formation >> Alpha-Haloethers OR SN1 >> Nucleophilic attack after diazonium or carbenium ion formation OR SN1 >> Nucleophilic attack after diazonium or carbenium ion formation >> Nitroarenes with Other Active Groups OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Single-Ring Substituted Primary Aromatic Amines OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Fused-Ring Nitroaromatics OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitroaniline Derivatives OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitroarenes with Other Active Groups OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR SN2 OR SN2 >> Acylation involving a leaving group  OR SN2 >> Acylation involving a leaving group  >> Geminal Polyhaloalkane Derivatives OR SN2 >> Acylation involving a leaving group after metabolic activation OR SN2 >> Acylation involving a leaving group after metabolic activation >> Geminal Polyhaloalkane Derivatives OR SN2 >> Alkylation, direct acting epoxides and related OR SN2 >> Alkylation, direct acting epoxides and related >> Epoxides and Aziridines OR SN2 >> Alkylation, direct acting epoxides and related after cyclization OR SN2 >> Alkylation, direct acting epoxides and related after cyclization >> Nitrogen Mustards 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 after thiol (glutathione) conjugation OR SN2 >> Nucleophilic substitution at sp3 carbon atom after thiol (glutathione) conjugation >> Geminal Polyhaloalkane Derivatives 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 OR SN2 >> SN2 attack on activated carbon Csp3 or Csp2 OR SN2 >> SN2 attack on activated carbon Csp3 or Csp2 >> Nitroarenes with Other Active Groups by DNA binding by OASIS v.1.3

Domain logical expression index: "g"

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

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates >> Benzylamines-Acylation OR 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 >> Alkyl phenols OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Arenes OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Hydroquinones OR Michael addition >> Polarised Alkenes-Michael addition OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated esters OR Schiff base formers OR Schiff base formers >> Chemicals Activated by P450 to Mono-aldehydes OR Schiff base formers >> Chemicals Activated by P450 to Mono-aldehydes >> Benzylamines-Schiff base OR Schiff base formers >> Direct Acting Schiff Base Formers OR Schiff base formers >> Direct Acting Schiff Base Formers >> Mono aldehydes OR SN1 OR SN1 >> Carbenium Ion Formation OR SN1 >> Carbenium Ion Formation >> Allyl benzenes 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 >> Aromatic nitro OR SN1 >> Nitrenium Ion formation >> Primary (unsaturated) heterocyclic amine OR SN1 >> Nitrenium Ion formation >> Primary aromatic amine OR SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine OR SN1 >> Nitrenium Ion formation >> Unsaturated heterocyclic azo by DNA binding by OECD

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Not possible to classify according to these rules by DPRA Lysine peptide depletion

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as High reactive OR High reactive >> Activated 1,3,5-triazine derivatives OR Low reactive OR Low reactive >> Activated haloarenes OR Low reactive >> N-substituted aromatic amides by DPRA Lysine peptide depletion

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Not possible to classify according to these rules by DPRA Cysteine peptide depletion

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Low reactive OR Low reactive >> Sulfanilic acid derivatives by DPRA Cysteine peptide depletion

Domain logical expression index: "m"

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

Domain logical expression index: "n"

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

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Vinyl/Allyl Nitriles by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "p"

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

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Vinyl/Allyl Nitriles by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "r"

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

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as Vinyl/Allyl Nitriles by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as Anilines (amino-meta) by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "u"

Referential boundary: The target chemical should be classified as Vinyl/Allyl Nitriles by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "v"

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

Domain logical expression index: "w"

Referential boundary: The target chemical should be classified as Vinyl/Allyl Nitriles by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "x"

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

Domain logical expression index: "y"

Referential boundary: The target chemical should be classified as Vinyl/Allyl Nitriles by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "z"

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: "aa"

Referential boundary: The target chemical should be classified as Vinyl/Allyl Nitriles by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "ab"

Referential boundary: The target chemical should be classified as Phenols, Poly by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "ac"

Referential boundary: The target chemical should be classified as Vinyl/Allyl Nitriles by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "ad"

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

Domain logical expression index: "ae"

Referential boundary: The target chemical should be classified as Vinyl/Allyl Nitriles by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "af"

Referential boundary: The target chemical should be classified as Triazines, Aromatic by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "ag"

Referential boundary: The target chemical should be classified as Not categorized by Repeated dose (HESS)

Domain logical expression index: "ah"

Referential boundary: The target chemical should be classified as Organophosphates (Neurotoxicity) Rank A by Repeated dose (HESS)

Domain logical expression index: "ai"

Parametric boundary:The target chemical should have a value of log Kow which is >= 1.39

Domain logical expression index: "aj"

Parametric boundary:The target chemical should have a value of log Kow which is <= 4.33

Validity criteria fulfilled:

not specified

Conclusions:

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, the toxicity to algae was predicted for the target substance (E)-3-phenylprop-2-enenitrile (CAS: 1885-38-7). EC50 Growth value was estimated to be 197.96 mg/l for Desmodesmus subspicatus for 72 hrs duration. It was concluded that (E)-3-phenylprop-2-enenitrile (CAS: 1885-38-7) likely to be not toxic to aquatic algae.

Executive summary:

Using the OECD QSAR toolbox version 3.3 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(E)-3-phenylprop-2-enenitrile (CAS: 1885-38-7).EC50 value was estimated to be 197.96 mg/l for Desmodesmus subspicatus for 72 h duration. Based on this value it can be concluded that the substance(E)-3-phenylprop-2-enenitrile (CAS: 1885-38-7)is considered to be non-toxic to aquatic environment and can be considered to be not classified as per the CLP classification criteria.

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, the toxicity to algae was predicted for the target substance (E)-3-phenylprop-2-enenitrile (CAS: 1885-38-7). EC50 Growth value was estimated to be 197.96 mg/l for Desmodesmus subspicatus for 72 hrs duration. It was concluded that (E)-3-phenylprop-2-enenitrile (CAS: 1885-38-7) likely to be not toxic to aquatic algae.

Key value for chemical safety assessment

EC50 for freshwater algae:

197.96 mg/L

Additional information

Toxicity to aquatic algae and cyanobacteria:

In Toxicity study of aquatic algae and cyanobacteria, prediction was done based on OECD QSAR toolbox for target substance (E)-3-phenylprop-2-enenitrile (1885-38-7),and for different experimental studies available on the structurally similar read across substance Benzaldehyde (100-52-7) and for benzene carboxylic acid (65-85-0). Studies included predicted as well as experimental data to conclude the toxicity extent of (E)-3-phenylprop-2-enenitrile (1885-38-7) 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 five closest read across substances, the toxicity to algae was predicted for the target substance (E)-3-phenylprop-2-enenitrile (CAS: 1885-38-7). EC50 Growth value was estimated to be 197.96 mg/l for Desmodesmus subspicatus for 72 hrs duration. It was concluded that (E)-3-phenylprop-2-enenitrile (CAS: 1885-38-7) likely to be not toxic to aquatic algae.

The above study was further supported by Stratton.G.W et. al. (Environ. Pollut. A.29(1): 71-80,1982) and U. S. Environmental Protection Agency (ECOTOX database, U. S. Environmental Protection Agency, 2017) for the structurally similar read across substance Benzaldehyde (100-52-7). Freshwater algal growth toxicity test was carried out on Anabaena inaequalis with the substance 100-52-7 (Benzaldehyde).The test substance was dissolved in water and test chemical was tested at a minimum of five concentrations ranging from 0 to 100 mg/l and all treatments were replicated five times. Nitrogenase activity was determined for A. inaequalis. The median effective concentration (EC50) for the test substance Benzaldehyde (100-52-7), in Anabaena inaequalis was determined to be >100 mg/L .This value indicates that the substance is likely to be non-hazardous to aquatic algae and cannot be classified as per the CLP criteria.

This is further supported by U. S. Environmental Protection Agency (ECOTOX database, U. S. Environmental Protection Agency, 2017) for the structurally similar read across substance benzene carboxylic acid (65-85-0).Freshwater algal toxicity test was carried out on Green Algae (Chlorococcales) with the substance carboxylic acid (65-85-0) on the basis of effects of Physiology (Assimilation efficiency) .The median effective concentration (EC50) for the test substance carboxylic acid (65-85-0), in Green Algae (Chlorococcales) was determined to be >100 mg/L .This value indicates that the substance is likely to be non-hazardous to aquatic algae and cannot be classified as per the CLP criteria.

Thus based on the effect concentrations which is in the range >100 mg/l to 197.96 mg/l give the conclusion that test substance (E)-3-phenylprop-2-enenitrile (1885-38-7) was likely to be non toxic to aquatic algae at environmentally relevant concentrations and can be considered to be “not classified” as per the CLP classification criteria.