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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 predicted using OECD QSAR toolbox version 3.4 and QMRF report has been attached
Qualifier:
according to guideline
Guideline:
other: estimated data
Principles of method if other than guideline:
Prediction was done by using OECD QSAR toolbox v3.4
GLP compliance:
not specified
Specific details on test material used for the study:
- Name of test material: 4-methoxy-2-methyl-N-phenylaniline
- IUPAC name: 4-methoxy-2-methyl-N-phenylaniline
- Molecular formula: C14H15NO
- Molecular weight: 213.279 g/mol
- Smiles: c1(c(cc(cc1)OC)C)Nc1ccccc1
- InChl: 1S/C14H15NO/c1-11-10-13(16-2)8-9-14(11)15-12-6-4-3-5-7-12/h3-10,15H,1-2H3
- Substance type: Organic
Analytical monitoring:
not specified
Details on sampling:
No data available
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.:
13.398 mg/L
Basis for effect:
mortality
Remarks on result:
other: No other details available

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 "n" )  and "o" )  and ("p" and ( not "q") )  )  and ("r" and ( not "s") )  )  and ("t" and ( not "u") )  )  and ("v" and ( not "w") )  )  and ("x" and ( not "y") )  )  and ("z" and ( not "aa") )  )  and "ab" )  and "ac" )  and ("ad" and ( not "ae") )  )  and ("af" and ( not "ag") )  )  and ("ah" and ( not "ai") )  )  and ("aj" and ( not "ak") )  )  and ("al" and "am" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as AN2 AND AN2 >> Michael-type addition to quinoid structures  AND AN2 >> Michael-type addition to quinoid structures  >> N-Substituted Aromatic Amines by Protein binding by OASIS v1.4

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Alkoxy OR Alkyl arenes OR Aromatic amine OR Aryl OR Ether OR Precursors quinoid compounds by Organic Functional groups ONLY

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Alkoxy OR Aromatic amine OR Ether OR Overlapping groups OR Precursors quinoid compounds 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 Aliphatic Nitrogen, two aromatic attach [-N-] OR Aromatic Carbon [C] OR Nitrogen, two or tree olefinic attach [>N-] 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 Amine OR Aromatic compound OR Ether OR Secondary amine OR Secondary aromatic amine 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 Protein binding by OECD

Domain logical expression index: "g"

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 Acylation >> Direct Acylation Involving a Leaving group >> Azlactone OR Michael addition OR Michael addition >> Polarised Alkenes OR Michael addition >> Polarised Alkenes >> Polarised alkene - aldehydes OR Schiff Base Formers OR Schiff Base Formers >> Direct Acting Schiff Base Formers OR Schiff Base Formers >> Direct Acting Schiff Base Formers >> Mono-carbonyls OR SN2 OR SN2 >> SN2 reaction at sp3 carbon atom OR SN2 >> SN2 reaction at sp3 carbon atom >> Alkyl halides OR SN2 >> SN2 reaction at sp3 carbon atom >> Allyl acetates and related chemicals OR SN2 >> SN2 reaction at sp3 carbon atom >> alpha-Haloalkynes (and related cyano, sulfate, sulphpnate subs. chem.) by Protein binding by OECD

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as AN2 AND AN2 >> Michael-type addition to quinoid structures  AND AN2 >> Michael-type addition to quinoid structures  >> N-Substituted Aromatic Amines by Protein binding by OASIS v1.4

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as SE reaction (CYP450-activated heterocyclic amines) >> Direct attack of arylnitrenium cation to the C8 position of nucleoside base  OR SE reaction (CYP450-activated heterocyclic amines) >> Direct attack of arylnitrenium cation to the C8 position of nucleoside base  >> Heterocyclic Aromatic Amines OR SR reaction (peroxidase-activated heterocyclic amines) OR SR reaction (peroxidase-activated heterocyclic amines) >> Direct attack of arylnitrenium radical to the C8 position of nucleoside base OR SR reaction (peroxidase-activated heterocyclic amines) >> Direct attack of arylnitrenium radical to the C8 position of nucleoside base >> Heterocyclic Aromatic Amines by Protein binding by OASIS v1.4

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as AN2 AND AN2 >> Michael-type addition to quinoid structures  AND AN2 >> Michael-type addition to quinoid structures  >> N-Substituted Aromatic Amines by Protein binding by OASIS v1.4

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as AN2 >> Michael-type addition to quinoid structures  >> Substituted Anilines by Protein binding by OASIS v1.4

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Class 5 (Not possible to classify according to these rules) by Acute aquatic toxicity classification by Verhaar (Modified) ONLY

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Class 5 (Not possible to classify according to these rules) by Acute aquatic toxicity classification by Verhaar (Modified) ONLY

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Class 5 (Not possible to classify according to these rules) by Acute aquatic toxicity classification by Verhaar (Modified) ONLY

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 Neutral Organics by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Not Related to an Existing ECOSAR Class OR Phenols OR Salt OR Substituted Ureas OR Triazines, Aromatic by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as Alkyl substituent on aromatic ring AND Aromatic amine   [-NH2  or  -NH-] AND Aromatic ether  [-O-aromatic carbon] AND Aromatic-CH3 AND Aromatic-H AND Benzene AND Methyl  [-CH3] AND Unsubstituted phenyl group (C6H5-) by Bioaccumulation - metabolism alerts

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as N-Alkane (linear) ... < C22 by Bioaccumulation - metabolism alerts

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as Alkyl substituent on aromatic ring AND Aromatic amine   [-NH2  or  -NH-] AND Aromatic ether  [-O-aromatic carbon] AND Aromatic-CH3 AND Aromatic-H AND Benzene AND Methyl  [-CH3] AND Unsubstituted phenyl group (C6H5-) by Bioaccumulation - metabolism alerts

Domain logical expression index: "u"

Referential boundary: The target chemical should be classified as Naphthalene OR Number of fused 5-carbon aromatic rings by Bioaccumulation - metabolism alerts

Domain logical expression index: "v"

Referential boundary: The target chemical should be classified as Alkyl substituent on aromatic ring AND Aromatic amine   [-NH2  or  -NH-] AND Aromatic ether  [-O-aromatic carbon] AND Aromatic-CH3 AND Aromatic-H AND Benzene AND Methyl  [-CH3] AND Unsubstituted phenyl group (C6H5-) by Bioaccumulation - metabolism alerts

Domain logical expression index: "w"

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

Domain logical expression index: "x"

Referential boundary: The target chemical should be classified as Alkyl substituent on aromatic ring AND Aromatic amine   [-NH2  or  -NH-] AND Aromatic ether  [-O-aromatic carbon] AND Aromatic-CH3 AND Aromatic-H AND Benzene AND Methyl  [-CH3] AND Unsubstituted phenyl group (C6H5-) by Bioaccumulation - metabolism alerts

Domain logical expression index: "y"

Referential boundary: The target chemical should be classified as Tertiary amine OR Unsubstituted aromatic (3 or less rings) OR Unsubstituted Cycloalkane by Bioaccumulation - metabolism alerts

Domain logical expression index: "z"

Referential boundary: The target chemical should be classified as Alkyl substituent on aromatic ring AND Aromatic amine   [-NH2  or  -NH-] AND Aromatic ether  [-O-aromatic carbon] AND Aromatic-CH3 AND Aromatic-H AND Benzene AND Methyl  [-CH3] AND Unsubstituted phenyl group (C6H5-) by Bioaccumulation - metabolism alerts

Domain logical expression index: "aa"

Referential boundary: The target chemical should be classified as Aromatic nitro  [-NO2] OR Aromatic-CH OR Aromatic-CH2 by Bioaccumulation - metabolism alerts

Domain logical expression index: "ab"

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

Domain logical expression index: "ac"

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

Domain logical expression index: "ad"

Referential boundary: The target chemical should be classified as Alkoxy AND Alkyl arenes AND Aromatic amine AND Aryl AND Ether AND Precursors quinoid compounds by Organic Functional groups

Domain logical expression index: "ae"

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

Domain logical expression index: "af"

Referential boundary: The target chemical should be classified as Alkoxy AND Aromatic amine AND Ether AND Overlapping groups AND Precursors quinoid compounds by Organic Functional groups (nested)

Domain logical expression index: "ag"

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

Domain logical expression index: "ah"

Referential boundary: The target chemical should be classified as Alkoxy AND Aromatic amine AND Ether AND Overlapping groups AND Precursors quinoid compounds by Organic Functional groups (nested)

Domain logical expression index: "ai"

Referential boundary: The target chemical should be classified as Terpenes by Organic Functional groups (nested)

Domain logical expression index: "aj"

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

Domain logical expression index: "ak"

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

Domain logical expression index: "al"

Parametric boundary:The target chemical should have a value of log Kow which is >= 2.96

Domain logical expression index: "am"

Parametric boundary:The target chemical should have a value of log Kow which is <= 4.06

Validity criteria fulfilled:
not specified
Conclusions:
EC 50 value of test chemical 4-methoxy-2-methyl-N-phenylaniline was estimated to be 13.39 mg/L when test chemical was exposed to Daphnia magna for 48 hrs.
Executive summary:

Toxicity to aquatic invertebrates of target chemical 4-methoxy-2-methyl-N-phenylaniline was estimated by using OECD QSAR tool box v3.4 using Log kow as primary descriptor and considering five closest read across substances. EC50 value of target chemical 4-methoxy-2-methyl-N-phenylaniline was estimated to be 13.39 mg/L when exposed to Daphnia magna for 48 hrs.

This EC50 value indicates that the substance is likely to be hazardous to aquatic invertebrates and can be classified as aquatic chronic 3 category as per the CLP criteria

Description of key information

Toxicity to aquatic invertebrates of target chemical 4-methoxy-2-methyl-N-phenylaniline was estimated by using OECD QSAR tool box v3.4 using Log kow as primary descriptor and considering five closest read across substances. EC50 value of target chemical 4-methoxy-2-methyl-N-phenylaniline was estimated to be 13.39 mg/L when exposed to Daphnia magna for 48 hrs.

This EC50 value indicates that the substance is likely to be hazardous to aquatic invertebrates and can be classified as aquatic chronic 3 category as per the CLP criteria

Key value for chemical safety assessment

Fresh water invertebrates

Fresh water invertebrates
Effect concentration:
13.39 mg/L

Additional information

Short-term toxicity to aquatic invertebrates:

Toxicity to aquatic invertebrates of target chemical 4-methoxy-2-methyl-N-phenylaniline was estimated by using OECD QSAR tool box v3.4 using Log kow as primary descriptor and considering five closest read across substances. EC50 value of target chemical 4-methoxy-2-methyl-N-phenylaniline was estimated to be 13.39 mg/L when exposed to Daphnia magna for 48 hrs.

This EC50 value indicates that the substance is likely to be hazardous to aquatic invertebrates and can be classified as aquatic chronic 3 category as per the CLP criteria

The above prediction was supported by experimental result conducted by Sustainability Support Services (Europe) AB for the structurally similar read across substance Methyl 2-naphthyl ether (93-04-9).

Determination of the inhibition of the mobility of daphnids was carried out with the substance Methyl 2-naphthyl ether according to OECD Guideline 202.

The test substance was tested at the concentrations 0, 5, 10, 20, 30, 40, 80 mg/L and the immobilisation effects were observed for 48 hours

The median effective concentration (EC50) for the test substance, Methyl 2-naphthyl ether, in Daphnia magna was determined to be 26 mg/L for immobilisation effects.

This value indicates that the substance is likely to be hazardous to aquatic invertebrates can can be classified as Aquatic chronic category 3 as per the CLP criteria.

Another experimental data describing the toxicity to aquatic invertebrates  for the structurally similar read across substance 4 methoxyaniline (104-94-9) conducted by Renate Kuhn, Monika Pattard, Klaus-Dieter Pernak and Angela Winter summarized in Wat. Res. Vol. 23, No. 4, pp. 495-499, 1989.

Short term toxicity test was performed on daphnia magna for 24 hrs treated with p-methoxyaniline. The test vessel containing 52 mg l- 1of test material in 50ml beaker. No feed was providing during test period. The test vessel was observed for 24 and 48 hrs.So on the basis of above experiment it was found that the Effective concentration 50 value for daphnia magna was found to be 52 mg l- 1in 24 hrs after treatment with p-methoxyaniline (104-94-9).

This value indicates that the substance is likely to be hazardous to aquatic invertebrates can can be classified as Aquatic chronic category 3 as per the CLP criteria.

Based on the available data for the target and read across substances and applying the weight of evidence approach the target chemical 4-methoxy-2-methyl-N-phenylaniline can be classified as Aquatic chronic category 3 as per the CLP criteria.