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

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:

QMRF report has been attached

Qualifier:

according to guideline

Guideline:

OECD Guideline 201 (Alga, Growth Inhibition Test)

Principles of method if other than guideline:

Prediction was done using the 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):

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

Test type:

static

Water media type:

freshwater

Total exposure duration:

72 h

Test temperature:

24 ± 1 ºC

pH:

7.2 - 7.7

Nominal and measured concentrations:

Estimated data

Reference substance (positive control):

not specified

Key result

Duration:

72 h

Dose descriptor:

EC50

Effect conc.:

2.9 mg/L

Nominal / measured:

estimated

Conc. based on:

test mat.

Basis for effect:

growth rate

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 5 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 ( not "i") )  )  and ("j" and ( not "k") )  )  and ("l" and ( not "m") )  )  and "n" )  and "o" )  and ("p" and ( not "q") )  )  and ("r" and ( not "s") )  )  and ("t" and ( not "u") )  )  and ("v" and "w" )  )

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 OASIS v.1.3

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Michael-type addition on alpha, beta-unsaturated carbonyl compounds OR AN2 >> Michael-type addition on alpha, beta-unsaturated carbonyl compounds >> Four- and Five-Membered Lactones OR AN2 >> Shiff base formation after aldehyde release OR AN2 >> Shiff base formation after aldehyde release >> Specific Acetate Esters OR Radical OR Radical >> Generation of reactive oxygen species OR Radical >> Generation of reactive oxygen species >> Thiols OR Radical >> Generation of ROS by glutathione depletion (indirect) OR Radical >> Generation of ROS by glutathione depletion (indirect) >> Haloalkanes Containing Heteroatom OR SN1 OR SN1 >> Carbenium ion formation OR SN1 >> Carbenium ion formation >> Alpha-Haloethers 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 >> Alkylation, direct acting epoxides and related OR SN2 >> Alkylation, direct acting epoxides and related >> Epoxides and Aziridines OR SN2 >> Alkylation, ring opening SN2 reaction OR SN2 >> Alkylation, ring opening SN2 reaction >> Four- and Five-Membered Lactones OR SN2 >> DNA alkylation OR SN2 >> DNA alkylation >> Alkylphosphates, Alkylthiophosphates and Alkylphosphonates OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Haloalkanes Containing Heteroatom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Specific Acetate Esters OR SN2 >> SN2 at sp3-carbon atom OR SN2 >> SN2 at sp3-carbon atom >> Alpha-Haloethers by DNA binding by OASIS v.1.3

Domain logical expression index: "f"

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

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Isocyanates and Isothiocyanates OR Acylation >> Isocyanates and Isothiocyanates >> Isocyanates 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 >> Polarised Alkenes-Michael addition OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated esters OR SN1 OR SN1 >> Iminium Ion Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines by DNA binding by OECD

Domain logical expression index: "h"

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

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Moderate binder, OH grooup OR Non binder, impaired OH or NH2 group OR Non binder, MW>500 OR Non binder, non cyclic structure OR Strong binder, OH group OR Weak binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as No alert found by Protein binding by OASIS v1.3

Domain logical expression index: "k"

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 >> Carbamates  OR Acylation >> Direct acylation involving a leaving group >> N-Acylated heteroaromatic amines  OR Acylation >> Ester aminolysis OR Acylation >> Ester aminolysis >> Amides OR Acylation >> Ester aminolysis or thiolysis OR Acylation >> Ester aminolysis or thiolysis >> Activated aryl esters  OR Acylation >> Ring opening acylation OR Acylation >> Ring opening acylation >> Active cyclic agents  OR Michael Addition OR Michael Addition >> Michael addition on conjugated systems with electron withdrawing group OR Michael Addition >> Michael addition on conjugated systems with electron withdrawing group >> alpha,beta-Carbonyl compounds with polarized double bonds  OR Nucleophilic addition OR Nucleophilic addition >> Addition to carbon-hetero double bonds OR Nucleophilic addition >> Addition to carbon-hetero double bonds >> Ketones OR SN2 OR SN2 >> Nucleophilic substitution on benzilyc carbon atom OR SN2 >> Nucleophilic substitution on benzilyc carbon atom >> alpha-Activated benzyls  OR SN2 >> SN2 Reaction at a sp3 carbon atom OR SN2 >> SN2 Reaction at a sp3 carbon atom >> Activated alkyl esters and thioesters  by Protein binding by OASIS v1.3

Domain logical expression index: "l"

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

Domain logical expression index: "m"

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 by Protein binding by OECD

Domain logical expression index: "n"

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: "o"

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

Domain logical expression index: "p"

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

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Surfactants-Nonionic by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "r"

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: "s"

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

Domain logical expression index: "t"

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: "u"

Referential boundary: The target chemical should be classified as Saturated heterocyclic fragment by Organic Functional groups

Domain logical expression index: "v"

Parametric boundary:The target chemical should have a value of log Kow which is >= 1.14

Domain logical expression index: "w"

Parametric boundary:The target chemical should have a value of log Kow which is <= 4.61

Validity criteria fulfilled:

not specified

Conclusions:

Based on the growth rate inhibition of algae, the EC50 value was estimated to be 2.89 mg/l when 2-(2,6-dimethyl-phenylamino)-propionic acid methyl esterexposed to Pseudokirchneriella subcapitata for 72hrs.  

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 five closest read across substances, toxicity on Pseudokirchneriella subcapitata (previous names: Raphidocelis subcapitata, Selenastrum capricornutum) was predicted for 2-(2,6-dimethyl-phenylamino)-propionic acid methyl ester (52888-49-0). Based on the growth rate inhibition of algae, the EC50 value was estimated to be 2.89 mg/l when 2-(2,6-dimethyl-phenylamino)-propionic acid methyl ester exposed to Pseudokirchneriella subcapitata for 72hrs.       

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 five closest read across substances, toxicity on Pseudokirchneriella subcapitata (previous names: Raphidocelis subcapitata, Selenastrum capricornutum) was predicted for 2-(2,6-dimethyl-phenylamino)-propionic acid methyl ester (52888-49-0). Based on the growth rate inhibition of algae, the EC50 value was estimated to be 2.89 mg/l when 2-(2,6-dimethyl-phenylamino)-propionic acid methyl ester exposed to Pseudokirchneriella subcapitata for 72hrs.       

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

EC50 for freshwater algae:

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 algae 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 five closest read across substances, toxicity on Pseudokirchneriella subcapitata (previous names: Raphidocelis subcapitata, Selenastrum capricornutum) was predicted for 2-(2,6-dimethyl- phenylamino)-propionic acid methyl ester (52888-49-0). Based on the growth rate inhibition of algae, the EC50 value was estimated to be 2.89 mg/l when 2-(2,6-dimethyl- phenylamino)-propionic acid methyl ester exposed to Pseudokirchneriella subcapitata for 72hrs. Based on this value it can be concluded that the substance 2-(2,6-dimethyl-ph enylamino)-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 by the structurally similar read across chemical (95-64-7) from J-check 2017, Study was conducted to determine the nature and effect of chemical 3,4-Dimethylaniline when comes in contact with algae. Test was performed according to the OECD Guideline 201 (Alga, Growth Inhibition Test). Test carried out by using static system in which green algae incubate with chemical for 72 hrs. After exposure of chemical some NOEC and EC50 was calculated. Based on the growth rate inhibition of green algae due to the effect of chemical 3,4-Dimethylaniline, the EC50 and NOEC was 8.6, 2.9 mg/l. But on the basis of AUG the EC50 was 4.6 and the NOEC was 2.9 mg/l. Thus chemical was classified as aquatic chronic 2 as per CLP classification criteria.

In the read across chemical (57837-19-1) from ECOTOX database toxicity on aquatic algae was observed. Aim of the study was to evaluate the toxicity of chemical Metalaxyl on the growth of aquatic algae. Test conducted in the static system for the total exposure period of 72hrs. After the incubation period EC50 was observed based on the effect on population of Pseudokirchneriella Subcapitata. Based on the effect of chemical Metalaxyl on the population of Pseudokirchneriella Subcapitata (Green Algae) after the exposure period of 72 hrs, the EC50 was 6.249 mg/l. Thus on the basis of EC50, it can be concluded that the chemical Metalaxyl was toxic to algae and can be consider to be classified as aquatic chronic category 3 as per the CLP classification criteria.

 

Similarly the third study was also supports the classification of chemical. The read across chemical was (51338-27-3) from ECOTOX database. Aim of the study was to evaluate the toxicity of chemical 2-(4-(2',4'-diclorofenoxi)-fenoxi)-metilpropanoato (Diclofop-methyl) on the growth of aquatic algae. Test conducted in the static system for the total exposure period of 72hrs. After the incubation period LOEC was observed based on the effect on biomass of blue green algae. Based on the effect of chemical 2-(4-(2',4'-diclorofenoxi)-fenoxi)- metilpropanoato (Diclofop-methyl) on the biomass of Blue-Green Algae Microcystis aeruginosa after the exposure period of 72 hrs, the LOEC was 5 mg/l. Thus on the basis of LOEC, it can be concluded that the chemical was toxic to algae 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.