4'-cyanoacetophenone

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

Qualifier:

according to guideline

Guideline:

other: As mention below

Principles of method if other than guideline:

Prediction was done using the OECD QSAR toolbox version 3.3.

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material : 4'-Cyanoacetophenone
- Molecular formula : C9H7NO
- Molecular weight : 145.16 g/mol
- Smiles notation : CC(=O)c1ccc(C#N)cc1
- InChl : 1S/C9H7NO/c1-7(11)9-4-2-8(6-10)3-5-9/h2-5H,1H3
- Substance type: Organic
- Physical state: Solid

Analytical monitoring:

not specified

Vehicle:

not specified

Test organisms (species):

Daphnia magna

Details on test organisms:

- Common name: Water flea

Test type:

static

Water media type:

freshwater

Total exposure duration:

48 h

Hardness:

132 mg/L as CaCO3

Test temperature:

20 +/- degrees celcius

pH:

8.2 to 8.6

Dissolved oxygen:

exceeded 60%

Nominal and measured concentrations:

Estimated data

Reference substance (positive control):

not specified

Key result

Duration:

48 h

Dose descriptor:

EC50

Effect conc.:

635.737 mg/L

Nominal / measured:

estimated

Conc. based on:

test mat.

Basis for effect:

other: Intoxication

Remarks on result:

other: Nontoxic

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 ( not "h") )  )  and ("i" and ( not "j") )  )  and ("k" and ( not "l") )  )  and "m" )  and ("n" and ( not "o") )  )  and "p" )  and "q" )  and "r" )  and "s" )  and "t" )  and ("u" and ( not "v") )  )  and "w" )  and "x" )  and ("y" and "z" )  )

Domain logical expression index: "a"

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

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Acetylenic Carbon [#C] OR Aliphatic Carbon [CH] OR Aliphatic Carbon [-CH2-] OR Aliphatic Carbon [-CH3] OR Aromatic Carbon [C] OR Carbonyl, aliphatic attach [-C(=O)-] OR Carbonyl, olefinic attach [-C(=O)-] OR Carbonyl, one aromatic attach [-C(=O)-] OR Cyano, aromatic attach [-C#N] OR Miscellaneous sulfide (=S) or oxide (=O) OR Olefinic carbon [=CH- or =C<] by Organic functional groups (US EPA) ONLY

Domain logical expression index: "c"

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

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Aryl OR Ketone OR Nitrile by Organic Functional groups ONLY

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 >> 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 SN1 OR SN1 >> Alkylation after metabolically formed carbenium ion species OR SN1 >> Alkylation after metabolically formed carbenium ion species >> Polycyclic Aromatic Hydrocarbon Derivatives OR SN2 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 >> Polycyclic Aromatic Hydrocarbon Derivatives OR SN2 >> Direct acting epoxides formed after metabolic activation OR SN2 >> Direct acting epoxides formed after metabolic activation >> Quinoline Derivatives OR SN2 >> SN2 at an activated carbon atom OR SN2 >> SN2 at an activated carbon atom >> Quinoline Derivatives 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 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 Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Polycyclic (PAHs) and heterocyclic (HACs) aromatic hydrocarbons-Michael addition 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 >> Primary aromatic amine by DNA binding by OECD

Domain logical expression index: "i"

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

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Non binder, impaired OH or NH2 group by Estrogen Receptor Binding

Domain logical expression index: "k"

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

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as 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  by Protein binding by OASIS v1.3

Domain logical expression index: "m"

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

Domain logical expression index: "n"

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

Domain logical expression index: "o"

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

Domain logical expression index: "p"

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

Domain logical expression index: "q"

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

Domain logical expression index: "r"

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

Domain logical expression index: "s"

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

Domain logical expression index: "t"

Similarity boundary:Target: CC(=O)c1ccc(C#N)cc1
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "u"

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

Domain logical expression index: "v"

Referential boundary: The target chemical should be classified as Valproic acid (Hepatotoxicity) Alert by Repeated dose (HESS)

Domain logical expression index: "w"

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

Domain logical expression index: "x"

Referential boundary: The target chemical should be classified as days - weeks by Biodeg primary (Biowin 4) ONLY

Domain logical expression index: "y"

Parametric boundary:The target chemical should have a value of log Kow which is >= -0.244

Domain logical expression index: "z"

Parametric boundary:The target chemical should have a value of log Kow which is <= 3.45

Validity criteria fulfilled:

not specified

Conclusions:

The EC50 value was estimated to be 635.7371 mg/l when 4'-Cyanoacetophenone exposed to Daphnia magna for 48hrs. 

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 six closest read across substances, toxicity on Daphnia magna was predicted for 4'-Cyanoacetophenone (1443-80-7). The EC50 value was estimated to be 635.7371 mg/l when 4'-Cyanoacetophenone exposed to Daphnia magna for 48hrs.  Based on this value it can be concluded that the substance is considered to not toxic to aquatic environment as per the criteria mentioned in 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 six closest read across substances, toxicity on Daphnia magna was predicted for 4'-Cyanoacetophenone (1443-80-7). The EC50 value was estimated to be 635.7371 mg/l when 4'-Cyanoacetophenone exposed to Daphnia magna for 48hrs.  Based on this value it can be concluded that the substance is considered to not toxic to aquatic environment as per the criteria mentioned in CLP regulation. 

Key value for chemical safety assessment

Fresh water invertebrates

Fresh water invertebrates

Effect concentration:

635.737 mg/L

Additional information

Based on the various predicted data for target chemical 4'-Cyanoacetophenone (1443-80-7) and experimental data for read across chemical studyhave been reviewed to determine the toxic nature of target chemical 4'-Cyanoacetophenone the studies are as mentioned below:

 

In the first predicted weight of evidence report for the 4'-Cyanoacetophenone (1443-80-7) from SSS (QSAR, 2017) toxicity study was carried out. 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, toxicity on Daphnia magna was predicted for 4'-Cyanoacetophenone (1443-80-7). The EC50 value was estimated to be 635.7371 mg/l when 4'-Cyanoacetophenone exposed to Daphnia magna for 48hrs.  Based on this value it can be concluded that the substance is considered to not toxic to aquatic environment as per the criteria mentioned in CLP regulation. 

 

In the second predicted weight of evidence report for the 4'-Cyanoacetophenone (1443-80-7) from EPIsuite, Based on the prediction done by EPI suite, ECOSAR version 1.1, on the basis of similarity of structure to chemicals for which the aquatic toxicity has been previously measured by structure-activity relationships (SARs) program, the LC 50 value for short term toxicity to aquatic invertebrates was predicted. On the basis of EPI suite, ECOSAR version 1.1, the LC 50 value for short term toxicity to aquatic invertebrates was predicted to be 315.775 mg/l for 4'-Cyanoacetophenone in 48 hrs. Based on this value it can be concluded that the 4'-Cyanoacetophenone is considered to be not toxic to aquatic environment and cannot be classified as per the criteria mentioned in CLP regulation.

 

Similarly in the third weight of evidence study for the RA chemical (586-37-8) from ABITEC lab, 2016, Determination of the inhibition of the mobility of daphnids was carried out with the substance 1-(3-methoxyphenyl)ethanone according to OECD Guideline 202. The test substance was tested at the concentrations 0, 3, 6, 12, 24, 50, and 100 mg/L. Effects on immobilisation were observed for 48 hours. The median effective concentration (EC50) for the test substance, 1-(3-methoxyphenyl)ethanone, in Daphnia magna was determined to be 21.4 mg/L for immobilisation effects. This value indicates that the substance 1-(3-methoxyphenyl)ethanone is likely to be hazardous to aquatic invertebrates and can be classified as aquatic chronic 3 as per the CLP criteria. But as the chemical 1-(3-methoxyphenyl)ethanone was readily biodegradable in water, so that the chemical was consider as nontoxic and can be consider to be not classified as per the CLP classification criteria.

 

Similarly fourth study was conducted for the read across chemical (100-47-0) from HSDB, ECOTOX, 2017. 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.

 

Similarly fifth weight of evidence study was conducted for the read across chemical (98-86-2) from GSBL, 2017. Study was conducted to determine the toxic effect of chemical 1-phenylethanone on the growth of daphnia magna. Also on tissue concentrations of different, narcotic active contaminants. Test was performed in the static system for 48hrs. Test medium used was US-APHA 1989. Static exposure in closed 20 ml injection vials was used in which 15 daphnia per vial incorporated with 8 replicates per test concentration added. 2 functional controls simultaneously run in the test. Chemical exposure at 23 °C with 16 h light and 8 h dark photoperiod. After the exposure of 48hrs effect concentration was measured. Based on the effect on the buoyancy of daphnia magna due to the exposure of chemical 1-phenylethanone, the EC0 was 528 mg/l.

 

Thus based on the above data sources for target chemical 4'-Cyanoacetophenone (1443-80-7) from various experimental studies and predicted studies from QSAR, ABITEC lab, HSDB, ECOTOX, GSBL, it was summarized that the chemical was nontoxic and can be consider to be not classified as toxic as per the CLP classification criteria.