4-methoxyphenylacetone

Short-term toxicity to fish

Link to relevant study record(s)

Reference

Endpoint:

short-term toxicity to fish

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 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
- Physical state: Colorless, oily liquid

Analytical monitoring:

not specified

Vehicle:

not specified

Test organisms (species):

Danio rerio (previous name: Brachydanio rerio)

Test type:

semi-static

Water media type:

freshwater

Total exposure duration:

96

Key result

Duration:

96 h

Dose descriptor:

LC50

Effect conc.:

463.202 mg/L

Nominal / measured:

estimated

Conc. based on:

test mat.

Basis for effect:

mortality (fish)

Remarks on result:

other: not toxic

Sublethal observations / clinical signs:

The prediction was based on dataset comprised from the following descriptors: LC50
Estimation method: Takes average value from the 6 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 ("j" and ( not "k") )  )  and ("l" and ( not "m") )  )  and ("n" and ( not "o") )  )  and "p" )  and "q" )  and "r" )  and "s" )  and "t" )  and "u" )  and "v" )  and "w" )  and ("x" and "y" )  )

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 Not possible to classify according to these rules by DPRA Cysteine peptide depletion

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as High reactive OR High reactive >> alpha,beta-carbonyl compounds with polarized multiple bonds OR Low reactive OR Low reactive >> Alicyclic ketones OR Low reactive >> Primary haloalkanes by DPRA Cysteine peptide depletion

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 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 >> Quinones and Quinone-type Chemicals OR Michael addition >> Quinones and Quinone-type Chemicals >> Quinones OR Schiff base formers OR Schiff base formers >> Chemicals Activated by P450 to Glyoxal  OR Schiff base formers >> Chemicals Activated by P450 to Glyoxal  >> Ethanolamines (including morpholine) 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 by DNA binding by OECD

Domain logical expression index: "g"

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

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as AN2 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 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 Radical OR Radical >> Radical mechanism by ROS formation (indirect) or direct radical attack on DNA OR Radical >> Radical mechanism by ROS formation (indirect) or direct radical attack on DNA >> Organic Peroxy Compounds OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Geminal Polyhaloalkane Derivatives 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 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 >> 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 by DNA binding by OASIS v.1.3

Domain logical expression index: "i"

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

Domain logical expression index: "j"

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

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Halogens by Groups of elements

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Group 14 - Carbon C AND Group 16 - Oxygen O by Chemical elements

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Group 15 - Nitrogen N by Chemical elements

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Lipid Solubility < 0.01 g/kg AND (!Undefined)Group C Surface Tension > 62 mN/m by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Group All Melting Point > 200 C OR Group C Melting Point > 55 C OR Group C Molecular Weight > 350 g/mol OR Group C Vapour Pressure < 0.0001 Pa by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "p"

Similarity boundary:Target: CC(=O)Cc1ccc(OC)cc1
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "q"

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: "r"

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: "s"

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: "t"

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

Domain logical expression index: "u"

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

Domain logical expression index: "v"

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

Domain logical expression index: "w"

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

Domain logical expression index: "x"

Parametric boundary:The target chemical should have a value of log Kow which is >= 1.1

Domain logical expression index: "y"

Parametric boundary:The target chemical should have a value of log Kow which is <= 2.31

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 fish was predicted 1-(4-methoxyphenyl)propan-2-one (CAS: 122-84-9). LC50 mortality value was estimated to be 463.2022 mg/l for Danio rerio for 96 hrs duration. It was concluded that 1-(4-methoxyphenyl)propan-2-one (CAS: 122-84-9) was likely to be not toxic to fish.

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 fish was predicted 1-(4-methoxyphenyl)propan-2-one (CAS: 122-84-9). LC50 mortality value was estimated to be 463.2022 mg/l for Danio rerio for 96 hrs duration. It was concluded that 1-(4-methoxyphenyl)propan-2-one (CAS: 122-84-9) was likely to be not toxic to fish.

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 fish was predicted 1-(4-methoxyphenyl)propan-2-one (CAS: 122-84-9). LC50 mortality value was estimated to be 463.2022 mg/l for Danio rerio for 96 hrs duration. It was concluded that 1-(4-methoxyphenyl)propan-2-one (CAS: 122-84-9) was likely to be not toxic to fish.

Key value for chemical safety assessment

Fresh water fish

Fresh water fish

Effect concentration:

463.202 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 fish 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 fish was predicted 1-(4-methoxyphenyl)propan-2-one (CAS: 122-84-9). LC50 mortality value was estimated to be 463.2022 mg/l for Danio rerio for 96 hrs duration. It was concluded that 1-(4-methoxyphenyl)propan-2-one (CAS: 122-84-9) was likely to be not toxic to fish.

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 UERL Lab report 2017, suggests that the Fish Acute Toxicity test according to OECD Guideline 203 was conducted for 4-methoxyphenylacetic acid. The nominal concentration selected for the experiment were 100mg/L and test fish were exposed to these concentration for 96 hours. The median lethal concentration (LC50) for 4-methoxyphenylacetic acid on Danio rerio in a 96 hours study on the basis of mortality effect was found to be >100 mg/L. Thus, on the basis of this LC50 value and according to CLP criteria for aquatic classification of the substance, it is concluded that the substance, 4-methoxyphenylacetic acid (CAS No. 104-01-8) does not exhibit short term toxicity to fish.

LC0 (96 hours) (highest loading at which no mortality was observed) = 100 mg/L

LC50 (96 hours) Experimental = >100 mg/L

Another supporting experimental study for the structurally similar read across Cyclohexanol (CAS: 108-93-0) from the handbook Acute Toxicities of Organic Chemicals to Fathead Minnows (Pimephales promelas), Vol. 1. 1984, also suggests that To study the effects of cyclohexanol on fish test was carried out for 96 hr under static condition. Mortality was measured during the test. Lethal concentration LC50 to 50% of Pimephales promelas when exposed to Cyclohexanol for 96 hr is 704 mg/L. It can be concluded from the value that the Cyclohexanol (CAS: 108-93-0)  is not toxic to the fishcan be considered as “not classified” as per the classification criteria for aquatic environment.

Thus based on the effect concentrations which is in the range >100 mg/L to704 mg/lgive the conclusion that test substance 1-(4-methoxyphenyl)propan-2-one (CAS: 122-84-9) is likely to be not toxic to fish at environmentally relevant concentrations and applying weight of evidence approach it can be considered to be “not classified” as per the CLP classification criteria.