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Short-term toxicity to aquatic invertebrates

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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 QMRF report has been attached.
Qualifier:
according to
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 test material (IUPAC name): 1-(4-methoxyphenyl)propan-2-one
- Common name: 4-Methoxyphenylacetone
- Molecular formula: C10H12O2
- Molecular weight: 164.203 g/mol
- Smiles notation: c1(ccc(OC)cc1)CC(C)=O
- InChl: 1S/C10H12O2/c1-8(11)7-9-3-5-10(12-2)6-4-9/h3-6H,7H2,1-2H3
- Substance type: Organic
Analytical monitoring:
not specified
Vehicle:
not specified
Test organisms (species):
Daphnia magna
Test type:
static
Water media type:
freshwater
Total exposure duration:
48 h
Key result
Duration:
48 h
Dose descriptor:
EC50
Effect conc.:
233.808 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 5 nearest neighbours
Domain  logical expression:Result: In Domain

(((((((((((((((((((("a" or "b" )  and ("c" and ( not "d") )  )  and ("e" and ( not "f") )  )  and ("g" and ( not "h") )  )  and ("i" and ( not "j") )  )  and "k" )  and "l" )  and ("m" and ( not "n") )  )  and ("o" and ( not "p") )  )  and ("q" and ( not "r") )  )  and ("s" and ( not "t") )  )  and "u" )  and "v" )  and "w" )  and "x" )  and "y" )  and ("z" and ( not "aa") )  )  and "ab" )  and "ac" )  and ("ad" and "ae" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Nucleophilic addition AND Nucleophilic addition >> Addition to carbon-hetero double bonds AND Nucleophilic addition >> Addition to carbon-hetero double bonds >> Ketones by Protein binding by OASIS v1.3

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Class 1 (narcosis or baseline toxicity) by Acute aquatic toxicity classification by Verhaar (Modified)

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

Domain logical expression index: "d"

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 >> 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 >> 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 >> Quinones OR Radical OR Radical >> Radical mechanism via ROS formation (indirect) 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) >> Quinones 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 >> Nucleophilic attack after carbenium ion formation OR SN1 >> Nucleophilic attack after carbenium ion formation >> Specific Acetate Esters 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 after metabolic activation OR SN2 >> Acylation involving a leaving group after metabolic activation >> Geminal Polyhaloalkane Derivatives OR SN2 >> Alkylation by epoxide metabolically formed after E2 reaction OR SN2 >> Alkylation by epoxide metabolically formed after E2 reaction >> Monohaloalkanes 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 >> Monohaloalkanes OR SN2 >> Direct acting epoxides formed after metabolic activation OR SN2 >> Direct acting epoxides formed after metabolic activation >> Quinoline Derivatives OR SN2 >> DNA alkylation 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 after carbenium ion formation OR SN2 >> Nucleophilic substitution after carbenium ion formation >> Monohaloalkanes OR SN2 >> Nucleophilic substitution at sp3 Carbon atom 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 by DNA binding by OASIS v.1.3

Domain logical expression index: "e"

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

Domain logical expression index: "f"

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 >> Arenes OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Hydroquinones 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 >> Secondary aromatic amine OR SN2 OR SN2 >> Epoxidation of Aliphatic Alkenes OR SN2 >> Epoxidation of Aliphatic Alkenes >> Halogenated polarised alkenes by DNA binding by OECD

Domain logical expression index: "g"

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

Domain logical expression index: "h"

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

Domain logical expression index: "i"

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

Domain logical expression index: "j"

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 OR SNAr OR SNAr >> Nucleophilic aromatic substitution OR SNAr >> Nucleophilic aromatic substitution >> Activated halo-benzenes by Protein binding by OECD

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Class 1 (narcosis or baseline toxicity) by Acute aquatic toxicity classification by Verhaar (Modified) ONLY

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Fast by Bioaccumulation - metabolism half-lives ONLY

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Alkyl substituent on aromatic ring AND Aromatic ether  [-O-aromatic carbon] AND Aromatic-CH2 AND Aromatic-H AND Benzene AND Ketone   [-C-C(=O)-C-] AND Methyl  [-CH3] by Bioaccumulation - metabolism alerts

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Number of fused 6-carbon aromatic rings by Bioaccumulation - metabolism alerts

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Alkyl substituent on aromatic ring AND Aromatic ether  [-O-aromatic carbon] AND Aromatic-CH2 AND Aromatic-H AND Benzene AND Ketone   [-C-C(=O)-C-] AND Methyl  [-CH3] by Bioaccumulation - metabolism alerts

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as o-Chloro / Mono-aromatic ether by Bioaccumulation - metabolism alerts

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Alkyl substituent on aromatic ring AND Aromatic ether  [-O-aromatic carbon] AND Aromatic-CH2 AND Aromatic-H AND Benzene AND Ketone   [-C-C(=O)-C-] AND Methyl  [-CH3] by Bioaccumulation - metabolism alerts

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as -CH-   [linear] by Bioaccumulation - metabolism alerts

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as Alkyl substituent on aromatic ring AND Aromatic ether  [-O-aromatic carbon] AND Aromatic-CH2 AND Aromatic-H AND Benzene AND Ketone   [-C-C(=O)-C-] AND Methyl  [-CH3] by Bioaccumulation - metabolism alerts

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as Aromatic amine   [-NH2  or  -NH-] by Bioaccumulation - metabolism alerts

Domain logical expression index: "u"

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

Domain logical expression index: "v"

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

Domain logical expression index: "w"

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

Domain logical expression index: "x"

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

Domain logical expression index: "y"

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

Domain logical expression index: "z"

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

Domain logical expression index: "aa"

Referential boundary: The target chemical should be classified as Aromatic hydrocarbons (Liver enzyme induction) Rank C OR Tamoxifen (Hepatotoxicity) Alert by Repeated dose (HESS)

Domain logical expression index: "ab"

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

Domain logical expression index: "ac"

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

Domain logical expression index: "ad"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.567

Domain logical expression index: "ae"

Parametric boundary:The target chemical should have a value of log Kow which is <= 3.13

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 invertebrate was predicted 1-(4-methoxyphenyl)propan-2-one (CAS: 122-84-9). EC50 Intoxication value was estimated to be 233.8082 mg/l for Daphnia magnafor 48 hrs duration. It was concluded that 1-(4-methoxyphenyl)propan-2-one (CAS: 122-84-9) was likely to be not toxic to aquatic invertebrate.
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 invertebrate was predicted 1-(4-methoxyphenyl)propan-2-one (CAS: 122-84-9). EC50 Intoxication value was estimated to be 233.8082 mg/l for Daphnia magnafor 48 hrs duration. It was concluded that 1-(4-methoxyphenyl)propan-2-one (CAS: 122-84-9) was likely to be not toxic to aquatic invertebrate.

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 invertebrate was predicted 1-(4-methoxyphenyl)propan-2-one (CAS: 122-84-9). EC50 Intoxication value was estimated to be 233.8082 mg/l for Daphnia magnafor 48 hrs duration. It was concluded that 1-(4-methoxyphenyl)propan-2-one (CAS: 122-84-9) was likely to be not toxic to aquatic invertebrate.

Key value for chemical safety assessment

EC50/LC50 for freshwater invertebrates:
233.808 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-methoxyphenyl)propan-2-one (CAS: 122-84-9) 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 closest read across substances, the toxicity to aquatic invertebrate was predicted 1-(4-methoxyphenyl)propan-2-one (CAS: 122-84-9). EC50 Intoxication value was estimated to be 233.8082 mg/l for Daphnia magnafor 48 hrs duration. It was concluded that 1-(4-methoxyphenyl)propan-2-one (CAS: 122-84-9) was likely to be not toxic to aquatic invertebrate.

The above predicted data of target chemical is supported by the experimental study of structurally similar read across 4-methoxyphenylacetic acid (CAS No. 104-01-8) from the ABITEC Lab report 2017, suggests that the Determination of the inhibition of the mobility of Daphnids was carried out with the substance4-methoxyphenylacetic acidaccording to OECD Guideline 202.

The stock solution 150.0 mg/L was prepared by dissolving white powder in reconstituted water. The solution was kept in ultrasonic bath for 20 min. The test solutions of required concentrations were prpared by mixing the stock solution of the test sample in reconstituted water.The test substance was tested at the concentrations 0, 30.0, 45.0, 67.5, 100.0 and 150.0 mg/L.The test was performed under static conditions in a fresh water system at a temperature of 20 °C± 1 °C. EC50 was calculated using non linear regression by the software Prism 4.0.

The median effective concentration (EC50) for the test substance,4-methoxyphenylacetic acid, in Daphnia magna was determined to be 100.8 mg/L for immobilisation effects with 95% CI of 94.7 to 107.4 mg/L. Thus, based on this EC50 value and after comparing with CLP criteria for aquatic classification of the substance it is concluded that the substance,4-methoxyphenylacetic aciddoes not exhibit short term toxicity to aquatic invertebrate (Daphnia Magna).

Another supporting experimental study for the structurally similar read across 4-Methoxybenzoic (p-anisic) acid from the Chemosphere 2005, also suggests that the acute immobilization toxicity of 4-Methoxybenzoic acid (p-Anisic acid) on the aromatic ring was determined for the freshwater crustacean Daphnia magna under neutralized condition. Test was performed in static system at different concentration ranges from 2-12 mmol/l. Neonates obtain from National Institute for Environmental Studies (NIES), Tsukuba, Japan. Daphnia feeds once daily on green alga Selenastrum capricornutum NIES-35. After the exposure of 24hrs no effect was observed. But after 48hrs with 4-Methoxybenzoic (p-anisic) acid the, EC50 was 943 mg/l with 95 % confidence interval of 8.55-1019.39 mg/l. (5.60-6.70 mmol/l). Thus based on the immobilization of daphnia magna due to 4-Methoxybenzoic (p-anisic) acid for 48hrs, EC50 was 943.318 mg/l.

Thus based on the effect concentrations which is in the range 100.8 mg/L to943.318 mg/lgive the conclusion that test substance 1-(4-methoxyphenyl)propan-2-one (CAS: 122-84-9) is 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.