Cinnamonitrile

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:

Data is predicted using 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

Details on sampling:

no data available

Vehicle:

not specified

Details on test solutions:

no data available

Test organisms (species):

Daphnia magna

Details on test organisms:

no data available

Test type:

static

Water media type:

freshwater

Limit test:

no

Total exposure duration:

48 h

Reference substance (positive control):

not specified

Duration:

48 h

Dose descriptor:

EC50

Effect conc.:

441.73 mg/L

Nominal / measured:

estimated

Conc. based on:

test mat.

Basis for effect:

other: Intoxication

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 6 nearest neighbours
Domain  logical expression:Result: In Domain

((((((((((((((((("a" or "b" or "c" or "d" )  and ("e" and ( not "f") )  )  and "g" )  and ("h" and ( not "i") )  )  and "j" )  and ("k" and ( not "l") )  )  and ("m" and ( not "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 "ah" )  )

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 >> Flavonoids 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 after aldehyde release OR AN2 >> Shiff base formation after aldehyde release >> Specific Acetate Esters OR AN2 >> Shiff base formation for aldehydes OR AN2 >> Shiff base formation for aldehydes >> Geminal Polyhaloalkane Derivatives OR AN2 >> Shiff base formation for aldehydes >> Haloalkane Derivatives with Labile Halogen OR AN2 >> Thioacylation via nucleophilic addition after cysteine-mediated thioketene formation OR AN2 >> Thioacylation via nucleophilic addition after cysteine-mediated thioketene formation >> Haloalkenes with Electron-Withdrawing Groups OR Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> Amino Anthraquinones OR Non-covalent interaction >> DNA intercalation >> Coumarins OR Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide Side Chain OR Non-covalent interaction >> DNA intercalation >> Quinones OR Non-specific OR Non-specific >> Incorporation into DNA/RNA, due to structural analogy with  nucleoside bases    OR Non-specific >> Incorporation into DNA/RNA, due to structural analogy with  nucleoside bases    >> Specific Imine and Thione Derivatives OR Radical OR Radical >> Generation of reactive oxygen species OR Radical >> Generation of reactive oxygen species >> Thiols OR Radical >> Generation of ROS by glutathione depletion (indirect) OR Radical >> Generation of ROS by glutathione depletion (indirect) >> Haloalkanes Containing Heteroatom OR Radical >> Radical mechanism by ROS formation OR Radical >> Radical mechanism by ROS formation >> Polynitroarenes OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Amino Anthraquinones OR Radical >> Radical mechanism via ROS formation (indirect) >> Conjugated Nitro Compounds OR Radical >> Radical mechanism via ROS formation (indirect) >> Coumarins OR Radical >> Radical mechanism via ROS formation (indirect) >> Flavonoids OR Radical >> Radical mechanism via ROS formation (indirect) >> Geminal Polyhaloalkane Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> Hydrazine 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) >> p-Aminobiphenyl Analogs OR Radical >> Radical mechanism via ROS formation (indirect) >> p-Substituted Mononitrobenzenes 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 >> Radical mechanism via ROS formation (indirect) >> Specific Imine and Thione Derivatives OR SN1 OR SN1 >> Alkylation after metabolically formed carbenium ion species OR SN1 >> Alkylation after metabolically formed carbenium ion species >> Polycyclic Aromatic Hydrocarbon Derivatives 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 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 >> Amino Anthraquinones OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> p-Aminobiphenyl Analogs 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 >> Conjugated Nitro Compounds 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 >> Nitrobiphenyls and Bridged Nitrobiphenyls OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Polynitroarenes OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> p-Substituted Mononitrobenzenes OR SN1 >> Nucleophilic substitution on diazonium ions OR SN1 >> Nucleophilic substitution on diazonium ions >> Specific Imine and Thione Derivatives OR SN2 OR SN2 >> Acylation OR SN2 >> Acylation >> Specific Acetate Esters OR SN2 >> Acylation involving a leaving group  OR SN2 >> Acylation involving a leaving group  >> Geminal Polyhaloalkane Derivatives OR SN2 >> Acylation involving a leaving group  >> Haloalkane Derivatives with Labile Halogen 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 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation OR SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation >> Haloalkenes with Electron-Withdrawing Groups OR SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation >> Polycyclic Aromatic Hydrocarbon Derivatives OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom >> Haloalkane Derivatives with Labile Halogen OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom >> Sulfonates and Sulfates OR SN2 >> Direct acting epoxides formed after metabolic activation OR SN2 >> Direct acting epoxides formed after metabolic activation >> Coumarins OR SN2 >> Direct acting epoxides formed after metabolic activation >> Quinoline Derivatives OR SN2 >> DNA alkylation OR SN2 >> DNA alkylation >> Alkylphosphates, Alkylthiophosphates and Alkylphosphonates OR SN2 >> DNA alkylation >> Vicinal Dihaloalkanes OR SN2 >> Internal SN2 reaction with aziridinium and/or cyclic sulfonium ion formation (enzymatic) OR SN2 >> Internal SN2 reaction with aziridinium and/or cyclic sulfonium ion formation (enzymatic) >> Vicinal Dihaloalkanes OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Haloalkanes Containing Heteroatom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Specific Acetate Esters 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 Reactive unspecified by Acute aquatic toxicity MOA by OASIS ONLY

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Non-Metals by Groups of elements

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Alkali Earth OR Halogens OR Metalloids OR Metals OR Transition Metals by Groups of elements

Domain logical expression index: "j"

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

Domain logical expression index: "k"

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

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Acetal OR Acrylamide OR Acrylate OR Alcohol OR Aliphatic Amine, primary OR Aliphatic Amine, secondary OR Alkane branched with quaternary carbon by Organic Functional groups

Domain logical expression index: "m"

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

Domain logical expression index: "n"

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

Domain logical expression index: "o"

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

Domain logical expression index: "p"

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

Domain logical expression index: "q"

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

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as Carbamic acid ester (uretane) by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "s"

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

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as Cation OR CO2 derivative (general) by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "u"

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

Domain logical expression index: "v"

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

Domain logical expression index: "w"

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

Domain logical expression index: "x"

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

Domain logical expression index: "y"

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

Domain logical expression index: "z"

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

Domain logical expression index: "aa"

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

Domain logical expression index: "ab"

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

Domain logical expression index: "ac"

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

Domain logical expression index: "ad"

Referential boundary: The target chemical should be classified as Phosphoric acid derivative OR Phosphoric acid ester OR Sulfenic acid derivative by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "ae"

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: "af"

Referential boundary: The target chemical should be classified as Pyridine, non fused rings  OR Sym-Triazine ring  by Organic functional groups (US EPA)

Domain logical expression index: "ag"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.728

Domain logical expression index: "ah"

Parametric boundary:The target chemical should have a value of log Kow which is <= 2.6

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 six closest read across substances, the toxicity to aquatic invertebrate was predicted for target substance (E)-3-phenylprop-2-enenitrile (CAS: 1885-38-7). EC50 Intoxication value was estimated to be 441.73 mg/l for Daphnia magna for 48 hrs duration. It was concluded that (E)-3-phenylprop-2-enenitrile (CAS: 1885-38-7) was likely to be not toxic to aquatic invertebrate.

Executive summary:

Using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the six closest read across substances, the short term toxicity on aquatic invertebrates was predicted for target substance (E)-3-phenylprop-2-enenitrile (CAS: 1885-38-7). EC50 value was estimated to be 441.73 mg/l for Daphnia magna for 48 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 six closest read across substances, the toxicity to aquatic invertebrate was predicted for target substance (E)-3-phenylprop-2-enenitrile (CAS: 1885-38-7). EC50 Intoxication value was estimated to be 441.73 mg/l for Daphnia magna for 48 hrs duration. It was concluded that (E)-3-phenylprop-2-enenitrile (CAS: 1885-38-7) was likely to be not toxic to aquatic invertebrate.

Key value for chemical safety assessment

Fresh water invertebrates

Fresh water invertebrates

Effect concentration:

441.73 mg/L

Additional information

Short term toxicity on aquatic invertebrate:

In Short term toxicity study of aquatic invertebrate, 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 benzoic acid(65-85-0) and for Benzonitrile(100-47-0). Studies included predicted as well as experimental data to conclude the toxicity extent of (E)-3-phenylprop-2-enenitrile (1885-38-7) towards aquatic invertebrate 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 six closest read across substances, the toxicity to aquatic invertebrate was predicted for target substance (E)-3-phenylprop-2-enenitrile (CAS: 1885-38-7). EC50 Intoxication value was estimated to be 441.73 mg/l for Daphnia magna for 48 hrs duration. It was concluded that (E)-3-phenylprop-2-enenitrile (CAS: 1885-38-7) was likely to be not toxic to aquatic invertebrate.

The above study was further supported by Yasushi Kamaya et. al. (Chemosphere 59 (2005) 255–261); IFA GESTIS (Gestis Substance Database ,2017) and U. S. Environmental Protection Agency (ECOTOX database, U. S. Environmental Protection Agency, 2017) for the structurally similar read across substance benzoic acid(65-85-0). Short term toxicity to aquatic invertebrates was performed in Daphnia magna for 48 hrs. The young daphnids were obtained from continuous cultures in 1 liter glass beakers at 21 ± 0.3 degree C, in dechlorinated and conditioned tap water, the medium was renewed in three weeks and daphnids were fed daily with the green alga Selenastrum capricornutum. The pH of test solution was adjusted to 7.45 ± 0.05 with HCL and NaOH. The concentrations of the resultant solutions were checked before and after (48 h) exposure using a UV–visible spectrophotometer. As the experiment starts neonate were placed in 50 ml of beaker with 40 ml of test solution. All experiment was made in four replicates and performed at 21 ± 0.3 degree C under 16 h light: 8 h dark photoperiod. Immobility was observed after 24 and 48 hrs and EC 50 value was calculated. After the experiment the EC 50 value of Benzoic acid (65-85-0) for Daphnia magna was determined to be 860 mg/l in 48 hrs.Based on the CLP regulation the benzoic acid is considered to be not toxic to aquatic invertebrates and can be concluded to be not classified.

This is further supported by U. S. National Library of Medicine (HSDB (Hazardous Substances Data Bank); US national Library of Medicine reviewed by SRC, 2017.) and U.S. Environment protection agency (U.S. Environment protection agency, 2017) for the structurally similar read across substance Benzonitrile(100-47-0). Determination of short term toxicity of Benzonitrile on the growth of aquatic invertebrates. Test was performed in the static system with the total exposure period of 24 hrs. <=24 h old daphnia magna were used in the study.After the exposure of 24hrs LC50 was determine on the basis of intoxication. Based on the intoxication of daphnia magna due to the exposure of chemical benzonitrile for 24hrs, the LC50 was 200 mg/l.Based on the LC50, it can be 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 which is in the range 200 mg/l to 860 mg/l give the conclusion that test substance (E)-3-phenylprop-2-enenitrile (1885-38-7) was likely to be not toxic to aquatic invertebrate at environmentally relevant concentrations and can be considered to be “not classified” as per the CLP classification criteria.