2-methylanisole

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: 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:

no

Specific details on test material used for the study:

- Name of test material: 2-methylanisole
- IUPAC name: 1-methoxy-2-methylbenzene
- Molecular formula: C8H10O
- Molecular weight: 122.166 g/mole
- Smiles : COc1ccccc1C
- Inchl: 1S/C8H10O/c1-7-5-3-4-6-8(7)9-2/h3-6H,1-2H3
- Substance type: Organic
- Physical state: Liquid (Colorless)

Analytical monitoring:

not specified

Vehicle:

not specified

Test organisms (species):

Raphidocelis subcapitata (previous names: Pseudokirchneriella subcapitata, Selenastrum capricornutum)

Test type:

static

Water media type:

freshwater

Limit test:

no

Total exposure duration:

72 h

Key result

Duration:

72 h

Dose descriptor:

EC50

Effect conc.:

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

Domain logical expression index: "a"

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: "b"

Referential boundary: The target chemical should be classified as Alkyl arenes OR Aryl OR Ether by Organic Functional groups ONLY

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Alkyl arenes OR Ether OR Overlapping groups by Organic Functional groups (nested) ONLY

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Aliphatic Carbon [CH] OR Aliphatic Carbon [-CH2-] OR Aliphatic Carbon [-CH3] OR Aromatic Carbon [C] OR Olefinic carbon [=CH- or =C<] OR Oxygen, one aromatic attach [-O-] by Organic functional groups (US EPA) ONLY

Domain logical expression index: "e"

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

Domain logical expression index: "f"

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

Domain logical expression index: "g"

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 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 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 >> 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 >> 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 acylation involving a leaving group OR SN2 >> Direct acylation involving a leaving group >> Acyl Halides 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 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: "h"

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

Domain logical expression index: "i"

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 >> Hydroquinones 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 >> SN2 at an sp3 Carbon atom OR SN2 >> SN2 at an sp3 Carbon atom >> Aliphatic halides by DNA binding by OECD

Domain logical expression index: "j"

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: "k"

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

Domain logical expression index: "l"

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: "m"

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

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Aliphatic Amines OR Not Related to an Existing ECOSAR Class OR Oxetanes OR Surfactants-Anionic OR Vinyl/Allyl Ethers OR Vinyl/Allyl Halides by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "o"

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

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as No alert found by rtER Expert System ver.1 - USEPA

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as 4-Alkylchlorobenzenes OR Alkylcyclohexanols OR Multi Cyclic Hydrocarbons by rtER Expert System ver.1 - USEPA

Domain logical expression index: "r"

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

Domain logical expression index: "s"

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

Domain logical expression index: "t"

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

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 3-Methylcholantrene (Hepatotoxicity) Alert OR Aliphatic/Alicyclic hydrocarbons (Alpha 2u-globulin nephropathy) Rank C OR Ethyleneglycol alkylethers (Hemolytic anemia) Rank A OR Valproic acid (Hepatotoxicity) Alert by Repeated dose (HESS)

Domain logical expression index: "w"

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

Domain logical expression index: "x"

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

Domain logical expression index: "y"

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

Domain logical expression index: "z"

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

Domain logical expression index: "aa"

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

Domain logical expression index: "ab"

Referential boundary: The target chemical should be classified as Alkyl arenes AND Ether AND Overlapping groups by Organic Functional groups (nested) ONLY

Domain logical expression index: "ac"

Referential boundary: The target chemical should be classified as Alkyl arenes AND Ether AND Overlapping groups by Organic Functional groups (nested) ONLY

Domain logical expression index: "ad"

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

Domain logical expression index: "ae"

Similarity boundary:Target: Cc1ccccc1OC
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "af"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.768

Domain logical expression index: "ag"

Parametric boundary:The target chemical should have a value of log Kow which is <= 3.01

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 short term toxicity on aquatic algae predicted for 1-methoxy-2-methylbenzene (CAS: 578-58-5). Effect concentration i.e EC50 value estimated to be 131.91 mg/l for Pseudokirchneriella subcapitata for 48 hrs duration. It can be concluded that the 1-methoxy-2-methylbenzene (CAS: 578-58-5) IS likely to be not toxic to aquatic algae, hence it can be considered to be “not classified” as per the CLP classification criteria for aquatic environment.

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 short term toxicity on aquatic algae predicted for 1-methoxy-2-methylbenzene (CAS: 578-58-5). Effect concentration i.e EC50 value estimated to be 131.91 mg/l for Pseudokirchneriella subcapitata for 48 hrs duration. It can be concluded that the 1-methoxy-2-methylbenzene (CAS: 578-58-5) IS likely to be not toxic to aquatic algae, hence it can be considered to be “not classified” as per the CLP classification criteria for aquatic environment.

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 short term toxicity on aquatic algae predicted for 1-methoxy-2-methylbenzene (CAS: 578-58-5). Effect concentration i.e EC50 value estimated to be 131.91 mg/l for Pseudokirchneriella subcapitata for 48 hrs duration. It can be concluded that the 1-methoxy-2-methylbenzene (CAS: 578-58-5)  IS likely to be not toxic to aquatic algae, hence it can be considered to be “not classified” as per the CLP classification criteria for aquatic environment.

Key value for chemical safety assessment

EC50 for freshwater algae:

131.91 mg/L

Additional information

Following studies include the predicted data and experimental study for the target chemical and structurally similar read across to conclude the 1-methoxy-2-methylbenzene (CAS: 578-58-5) toxicity 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 closest read across substances, the short term toxicity on aquatic algae predicted for 1-methoxy-2-methylbenzene (CAS: 578-58-5). Effect concentration i.e EC50 value estimated to be 131.91 mg/l for Pseudokirchneriella subcapitata for 48 hrs duration. It can be concluded that the 1-methoxy-2-methylbenzene (CAS: 578-58-5)  IS likely to be not toxic to aquatic algae, hence it can be considered to be “not classified” as per the CLP classification criteria for aquatic environment.

The above predicted data of target chemical is supported by the experimental study of structurally similar read across 2-methylpropan-1-ol(CAS: 78-83-1) from publicationWater Research 1990, suggests that In the Scenedesmus cell multiplication inhibition test, hazardous substances were examined to determine the effect concentrations (EC). The tests were conducted in accordance with the test procedure DIN 38 412, Part 9 (draft standard). The green alga Scenedesmus subspicatus CHODAT was cultivated as the test organism. Decreasing trend of Population changes effect were measured. The Effective concentration EC50 to 50% of Scenedesmus subspicatus is 230 mg/l. It can be concluded that the 2-methylpropan-1-ol is not toxic to the aquatic ALGAE .

Similar experimental study of another structurally similar read acrossHexan-1-ol (CAS: 111-27-3) from publicationSAR and QSAR in Environmental Research 1980,indicates that the Toxicity to aquatic algae and cyanobacteria test was carried out for 2 mins to study the effects of Hexan-1-ol in aquatic algae. The conductivity of samples 1 and 2 was measured and used to derive an ion retention health index. This index reflects the proportion of the total leechable ions present in the thallus which were retained after exposure to distilled water for 2 mins. The effective concentration EC50 TO 50% of Enteromorpha intestinalis in 2 mins is 400 mg/l. It can be concluded from the value that the Hexan-1-ol is not toxic to the aquatic algae.

Thus based on the effect concentrations which is in the range 131.91 mg/l to 400 mg/l give the conclusion that test substance 1-methoxy-2-methylbenzene (CAS: 578-58-5) was likely to be not toxic to aquatic algae at environmentally relevant concentrations and applying weight of evidence approach it can be considered to be“not classified”as per the CLP classification criteria.