Methyl N-(2,6-dimethylphenyl)-DL-alaninate

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:

QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: Estimated data

Principles of method if other than guideline:

Prediction was done using OECD QSAR toolbox version 3.3.

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material : 2-(2,6-dimethyl-phenylamino)-propionic acid methyl ester
- Common name : Methyl N-(2,6-dimethylphenyl)-DL-alaninate
- Molecular formula : C12H17NO2
- Molecular weight : 207.271 g/mol
- Smiles notation : N(c1c(cccc1C)C)[C@@H](C(OC)=O)C
- InChl : 1S/C12H17NO2/c1-8-6-5-7-9(2)11(8)13-10(3)12(14)15-4/h5-7,10,13H,1-4H3
- 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:

150 - 180 mg/L CaCO3

Test temperature:

22 -23 °C

pH:

7.9 - 8.5

Dissolved oxygen:

6.0 - 8.6 mg/L

Nominal and measured concentrations:

Estimated data

Reference substance (positive control):

not specified

Key result

Duration:

48 h

Dose descriptor:

EC50

Effect conc.:

2.898 mg/L

Nominal / measured:

estimated

Conc. based on:

not specified

Basis for effect:

other: Intoxication

Remarks on result:

other: Other details not known

Details on results:

The EC50 was 2.89 mg/l

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" )  and ("d" and ( not "e") )  )  and ("f" and ( not "g") )  )  and "h" )  and ("i" and ( not "j") )  )  and "k" )  and ("l" and ( not "m") )  )  and "n" )  and ("o" and ( not "p") )  )  and ("q" and "r" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Esters (Acute toxicity) by US-EPA New Chemical Categories

Domain logical expression index: "b"

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

Domain logical expression index: "c"

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

Domain logical expression index: "d"

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

Domain logical expression index: "e"

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 >> Formamides OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates >> Sulfonylureas OR Michael addition OR Michael addition >> P450 Mediated Activation of Heterocyclic Ring Systems OR Michael addition >> P450 Mediated Activation of Heterocyclic Ring Systems >> Furans 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 >> Polarised Alkenes-Michael addition OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated esters OR Michael addition >> Quinones and Quinone-type Chemicals OR Michael addition >> Quinones and Quinone-type Chemicals >> Quinones OR SN1 OR SN1 >> Carbenium Ion Formation OR SN1 >> Carbenium Ion Formation >> Allyl benzenes OR SN1 >> Iminium Ion Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines OR SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >> Aromatic nitro OR SN1 >> Nitrenium Ion formation >> Primary aromatic amine OR SN1 >> Nitrenium Ion formation >> Secondary aromatic amine OR SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine OR SN2 OR SN2 >> P450 Mediated Epoxidation OR SN2 >> P450 Mediated Epoxidation >> Coumarins OR SN2 >> SN2 at an sp3 Carbon atom OR SN2 >> SN2 at an sp3 Carbon atom >> Sulfonates by DNA binding by OECD

Domain logical expression index: "f"

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

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Non binder, MW>500 OR Non binder, non cyclic structure OR Strong binder, OH group OR Very strong binder, OH group OR Weak binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Class 3 (unspecific reactivity) by Acute aquatic toxicity classification by Verhaar (Modified) ONLY

Domain logical expression index: "i"

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

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Acid moiety OR Aliphatic Amines OR Amides OR Halopyrdines OR Hydrazines OR Pyrazoles/Pyrroles OR Thiocyanates OR Vinyl/Allyl Ethers by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "k"

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

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Alkyl arenes AND Carboxylic acid ester AND Overlapping groups AND Precursors quinoid compounds by Organic Functional groups (nested)

Domain logical expression index: "m"

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

Domain logical expression index: "n"

Similarity boundary:Target: CC(C(=O)OC)Nc1c(C)cccc1C
Threshold=10%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "o"

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

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Fused heterocyclic aromatic by Organic Functional groups

Domain logical expression index: "q"

Parametric boundary:The target chemical should have a value of log Kow which is >= 1.66

Domain logical expression index: "r"

Parametric boundary:The target chemical should have a value of log Kow which is <= 4.95

Validity criteria fulfilled:

not specified

Conclusions:

Based on the intoxication of test organism the EC50 value was estimated to be 2.89 mg/l when 2-(2,6-dimethyl-phenylamino)-propionic acid methyl ester exposed to daphnia magna for 48 hrs.

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 2-(2,6-dimethyl-phenylamino)-propionic acid methyl ester (52888-49-0). Based on the intoxication of test organism the EC50 value was estimated to be 2.89 mg/l when 2-(2,6-dimethyl-phenylamino)-propionic acid methyl ester exposed to daphnia magna for 48 hrs. Based on this value it can be concluded that the substance 2-(2,6-dimethyl-phenylamino)-propionic acid methyl ester is considered to be toxic to aquatic environment and can classified as aquatic chronic 2 category 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 2-(2,6-dimethyl-phenylamino)-propionic acid methyl ester (52888-49-0). Based on the intoxication of test organism the EC50 value was estimated to be 2.89 mg/l when 2-(2,6-dimethyl-phenylamino)-propionic acid methyl ester exposed to daphnia magna for 48 hrs. Based on this value it can be concluded that the substance 2-(2,6-dimethyl-phenylamino)-propionic acid methyl ester is considered to be toxic to aquatic environment and can classified as aquatic chronic 2 category per the criteria mentioned in CLP regulation.      

Key value for chemical safety assessment

Fresh water invertebrates

Fresh water invertebrates

Effect concentration:

2.89 mg/L

Additional information

Various predicted data for the target compound 2-(2,6-dimethyl-phenylamino)-propionic acid methyl ester (52888-49-0) and experimental for supporting weight of evidence studies for its closest read across substance with log Kow as the primary descriptor and on the basis of structural and functional similarity were reviewed for the toxicity on the invertebrates end point which are summarized as below: 

In a prediction done by SSS (2017), 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 2-(2,6-dimethyl-phenylamino)-propionic acid methyl ester (52888-49-0). Based on the intoxication of test organism the EC50 value was estimated to be 2.89 mg/l when 2-(2,6-dimethyl-phenylamino)-propionic acid methyl ester exposed to daphnia magna for 48 hrs. Based on this value it can be concluded that the substance 2-(2,6-dimethyl-phenylamino)-propionic acid methyl ester is considered to be toxic to aquatic environment and can classified as aquatic chronic 2 category per the criteria mentioned in CLP regulation.      

 

First predicted study was supported was supported by the structurally similar read across chemical (87-59-2) study were to determine the toxicity of a chemical. Study was conducted to evaluate the toxic nature of chemical 2,3-Dimethylanilin on the mobility of daphnia magna for 48 hrs. Study was performed according to OECD Guideline 202 “Daphnia sp., Acute Immobilisation Test and Reproduction Test”. Static system used in which daphnia incubates with chemical under proper conditions of temperature and pH. Analysis done by the HPLC. Test solution volume 100 mL/vessel was used in which 20 daphnia per concentration added. Test conducted in 4 replicates. Based on the effect on the mobility of test organism daphnia magna due to the exposure of chemical 2,3-Dimethylanilin, the EC50 was 8.9 mg/l with 95 % CL was 7.0 - 12 mg/L. Based on the EC50, it can be concluded that the chemical was toxic to aquatic invertebrates and can be consider to be classified as per the CLP classification criteria.

 

Similarly in a supporting weight of evidence study from j-check, for read across chemical (95-64-7) from J-check 2017, Study was conducted to determine the nature of chemical 3,4-Dimethylaniline when comes in contact with daphnia species. Test performed according to the OECD Guideline 202 (Daphnia sp. Acute Immobilisation Test) in the static system. Test organism exposed with chemical for 48hrs in the proper conditions. After the exposure period effect concentration at which 50% growth inhibited was observed. As the test performed according to the OECD Guideline 202 (Daphnia sp. Acute Immobilisation Test), the EC50 was 1.1 mg/l after the exposure of chemical with test organism for 48 hrs. Based on the EC50, it can be concluded that the chemical was toxic and can be consider to be classified as chronic category 2 as per the CLP classification criteria.

 

The fourth study was conducted on the read across chemical selected on the basis of structure and functionally similarity chemical (131-11-3) from ECOTOX, 2017. Study was conducted to determine the toxic nature of chemical 1,2-Benzenedicarboxylic acid, dimethyl ester on the growth of aquatic invertebrates. Study was conducted by following the static system with the total exposure period of 48 hrs. After 48hrs of exposure effect on the growth of daphnia magna was observed on the basis of immobility. On the basis of immobility of daphnia magna, due to the exposure with chemical 1,2-Benzenedicarboxylic acid, dimethyl ester, the NOEC was 1.7 mg/l.

 

Similarly the fifth study was also supports the classification of chemical. The read across chemical was (51338-27-3) from ECOTOX database. Study was conducted to determine the nature of chemical when comes in contact with the aquatic invertebrates daphnia magna. Test organism exposed for 48hrs with the chemical 2-(4-(2',4'-diclorofenoxi)-fenoxi)-metilpropanoato. In the static conditions test was performed. Immobility of daphnia magna was measured at the effect concentration at which 50 % immobility was observed. Based on the intoxication of daphnia magna due to the exposure of chemical 2-(4-(2',4'-diclorofenoxi)-fenoxi)-metilpropanoato with the daphnia magna for the 48 hrs, EC50 was 1.06 mg/l. Thus based on the EC50, it can be concluded that the chemical was toxic and can be consider to be classified as aquatic chronic category 3 as per the CLP classification criteria.

 

On the basis of above results for target chemical 2-(2,6-dimethyl-phenylamino)-propionic acid methyl ester (52888-49-0) (from OECD QSAR toolbox version 3.3) and for its read across substance from j-check and ECOTOX database it can be concluded that the test substance 2-(2,6-dimethyl-phenylamino)-propionic acid methyl ester (52888-49-0) is toxic to aquatic environment and can classified as aquatic chronic 2 category per the criteria mentioned in CLP regulation.