N-[3-(diethylamino)phenyl]acetamide

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:

The supporting QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: Refer below principle

Principles of method if other than guideline:

The data is predicted using the OECD QSAR toolbox version 3.3 with logKow as the primary descriptor.

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material: N-[3-(diethylamino)phenyl]acetamide
- Molecular formula: C12H18N2O
- Molecular weight: 206.287 g/mol
- Smiles notation: O=C(Nc1cccc(N(CC)CC)c1)C
- InChl: 1S/C12H18N2O/c1-4-14(5-2)12-8-6-7-11(9-12)13-10(3)15/h6-9H,4-5H2,1-3H3,(H,13,15)
- 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:

23 deg.C

pH:

7.8

Reference substance (positive control):

not specified

Key result

Duration:

72 h

Dose descriptor:

EC50

Effect conc.:

440.58 mg/L

Nominal / measured:

estimated

Conc. based on:

test mat.

Basis for effect:

growth rate

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 ("k" and ( not "l") )  )  and ("m" and "n" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as SN1 AND SN1 >> Nitrenium Ion formation AND SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine by DNA binding by OECD

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Acylation AND Acylation >> Ester aminolysis AND Acylation >> Ester aminolysis >> Amides by Protein binding by OASIS v1.3

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Acylation AND Acylation >> Direct Acylation Involving a Leaving group AND Acylation >> Direct Acylation Involving a Leaving group >> Acetates by Protein binding by OECD

Domain logical expression index: "d"

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

Domain logical expression index: "e"

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, NH2 group OR Strong binder, OH group OR Very strong binder, OH group OR Weak binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Acylation AND Acylation >> Direct Acylation Involving a Leaving group AND Acylation >> Direct Acylation Involving a Leaving group >> Acetates by Protein binding by OECD

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Acylation >> Direct Acylation Involving a Leaving group >> Anhydrides OR Acylation >> Direct Acylation Involving a Leaving group >> Azlactone OR Acylation >> Ring Opening Acylation OR Acylation >> Ring Opening Acylation >> alpha-Lactams OR Michael addition OR Michael addition >> Acid imides OR Michael addition >> Acid imides >> Acid imides-MA OR Michael addition >> Polarised Alkenes OR Michael addition >> Polarised Alkenes >> Polarised alkene - amides OR Michael addition >> Polarised Alkenes >> Polarised alkene - esters OR Michael addition >> Polarised Alkenes >> Polarised alkene - ketones OR No alert found OR SN2 OR SN2 >> Epoxides and Related Chemicals OR SN2 >> Epoxides and Related Chemicals >> Epoxides OR SN2 >> SN2 reaction at sp3 carbon atom OR SN2 >> SN2 reaction at sp3 carbon atom >> Alkyl diazo OR SN2 >> SN2 reaction at sp3 carbon atom >> alpha-Halocarbonyls OR SNAr OR SNAr >> Nucleophilic aromatic substitution OR SNAr >> Nucleophilic aromatic substitution >> Activated halo-benzenes by Protein binding by OECD

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Not possible to classify according to these rules (GSH) by Protein binding potency

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Highly reactive (GSH) OR Highly reactive (GSH) >> 3-Alken-2-ones (MA) OR Moderately reactive (GSH) OR Moderately reactive (GSH) >> Substituted 1-Alken-3-ones (MA) OR Slightly reactive (GSH) OR Slightly reactive (GSH) >> Substituted haloacetamides (SN2) by Protein binding potency

Domain logical expression index: "j"

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: "k"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Lipid Solubility < 0.01 g/kg AND (!Undefined)Group CN Lipid Solubility < 0.4 g/kg AND Group CN Vapour Pressure < 0.001 Pa by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as (!Undefined)Group C Surface Tension > 62 mN/m OR (!Undefined)Group CNS Surface Tension > 62 mN/m OR Group All log Kow < -3.1 OR Group All log Kow > 9 OR Group All Melting Point > 200 C OR Group C Aqueous Solubility < 0.0001 g/L OR Group C Melting Point > 55 C OR Group C Molecular Weight > 350 g/mol OR Group C Vapour Pressure < 0.0001 Pa OR Group CN Aqueous Solubility < 0.0001 g/L OR Group CN Aqueous Solubility < 0.1 g/L OR Group CN log Kow > 4.5 OR Group CN log Kow > 5.5 OR Group CN Melting Point > 180 C OR Group CN Molecular Weight > 290 g/mol OR Group CNS log Kow < 0.5 OR Group CNS Melting Point > 120 C OR Group CNS Melting Point > 50 C by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "m"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.247

Domain logical expression index: "n"

Parametric boundary:The target chemical should have a value of log Kow which is <= 3.61

Validity criteria fulfilled:

not specified

Conclusions:

Using OECD QSAR toolbox version 3.3 the median Effective concentration (EC50) value for test chemical N-[3-(diethylamino)phenyl]acetamide on Pseudokirchneriella subcapitata in a 72 hour study was estimated to be 440.58 mg/L on the basis of effects on growth rate.

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, the short term toxicity on aquatic algae and cyanobacteria was predicted for target substance N-[3-(diethylamino)phenyl]acetamide. EC50 value was estimated to be 440.58 mg/l for Pseudokirchneriella subcapitata for 72 h duration. This effect value indicating that the substance N-[3-(diethylamino)phenyl]acetamide (CAS no. 6375-46-8) does not pose a significant hazard to algae and thus consider to be not classifies as per the CLP classification criteria.

Description of key information

Using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the five closest read across substances, the short term toxicity on aquatic algae and cyanobacteria was predicted for target substance N-[3-(diethylamino)phenyl]acetamide . EC50 value was estimated to be 440.58 mg/l for Pseudokirchneriella subcapitata for 72 h duration. This effect value indicating that the substance N-[3-(diethylamino)phenyl]acetamide (CAS no. 6375-46-8) does not pose a significant hazard to algae and thus consider to be not classifies as per the CLP classification criteria.

Key value for chemical safety assessment

EC50 for freshwater algae:

440.58 mg/L

Additional information

Four studies including predicted data from validated tool and experimental data from authorative database for toxicity to aquatic algae endpoint of test chemical N-[3-(diethylamino)phenyl]acetamide (Cas no. 6375-46-8) with relevant read across which is close to target using log Kow as primary descriptor were summarised as follows:

 

Using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the six closest read across substances, which indicate the short term toxicity on aquatic algae and cyanobacteria was predicted for target substance N-[3-(diethylamino)phenyl]acetamide (Cas no. 6375-46-8) .The EC50 value was estimated to be 440.58 mg/l for Pseudokirchneriella subcapitata for 72 h duration. 

 

Above predicted result for target assist by experimental data of read across chemical Caprolactam (Cas no. 105-60-2) from authorative database Japan chemicals collaborative knowledge database (J-check), 2017; indicate toxicity to green algae study was carried out according to OECD Guideline 201 (Alga, Growth Inhibition Test) .The study was based on the growth rate effects of the test compound Caprolactam (Cas no.105-60-2) on green algae. Based on growth effects the EC50 value was observed to be >1000 mg/l and no observed effect concentration (NOEC) was observed to be 1000 mg/l.

 

Another read across Dodecane-12-lactam (Cas no. 947-04-6) from same data source i.e (J-check), 2017 suggest Toxicity to green algae study was carried out .The study was based on the growth rate effects of the test compound Dodecane-12-lactam (Cas no.947-04-6)on green algae. Based on growth effects the EC50 value was observed to be >100 mg/l and no observed effect concentration (NOEC) was observed to be 16 mg/l.

And read across 1-ethenylpyrrolidin-2-one (Cas no. 88-12-0) indicate According to experimental method the 50 percent inhibition of reproduction (EC50) and 50 percent reduction in inhibition of growth rate of chemical 1-ethenylpyrrolidin-2-one in test species Scenedesmus subspicatus was observed to be 770 mg/L and >1000 mg/L, respectively. (OECD HPV Chemical Programme, 2010)

Thus based on the various effects from all above studies give the conclusion that test substance N-[3-(diethylamino)phenyl]acetamide (Cas no. 6375-46-8) was likely to be non toxic to aquatic algae as it not meet the classification criteria of aquatic toxicity as per the CLP regulation.