N-benzyl-N-ethylaniline

Endpoint summary

Description of key information

In a prediction done by SSS (2017) using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor, the acute oral toxicity was estimated for N-benzyl-N-ethylaniline. The LD50 was estimated to be 1042.3 mg/kg bw when rats were orally exposed with N-benzyl-N-ethylaniline. 

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

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 3.4 and the supporting QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: Refer below principle

Principles of method if other than guideline:

Prediction is done using OECD QSAR toolbox version 3.4, 2017

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Specific details on test material used for the study:

- Name of test material: N-benzyl-N-ethylaniline
- IUPAC anem: N-benzyl-N-ethylaniline
- Molecular formula: C15H17N
- Molecular weight : 211.306 g/mol
- Smiles notation: N(c1ccccc1)(Cc1ccccc1)CC
- InChl: 1S/C15H17N/c1-2-16(15-11-7-4-8-12-15)13-14-9-5-3-6-10-14/h3-12H,2,13H2,1H3
- Substance type: Organic
- Physical state: Liquid

Species:

rat

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

No data

Route of administration:

other: Oral

Vehicle:

not specified

Details on oral exposure:

No data

Doses:

1042.3 mg/Kg bw

No. of animals per sex per dose:

No data

Control animals:

not specified

Details on study design:

No data

Statistics:

No data

Preliminary study:

No data

Sex:

not specified

Dose descriptor:

LD50

Effect level:

1 042.309 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 50% mortality observed

Mortality:

50% mortality

Clinical signs:

other: No data

Gross pathology:

No data

Other findings:

No data

The prediction was based on dataset comprised from the following descriptors: LD50
Estimation method: Takes average value from the 6 nearest neighbours
Domain  logical expression:Result: In Domain

(((((((((((("a" or "b" or "c" or "d" )  and ("e" and ( not "f") )  )  and ("g" and ( not "h") )  )  and ("i" and ( not "j") )  )  and "k" )  and ("l" and ( not "m") )  )  and ("n" and ( not "o") )  )  and ("p" and ( not "q") )  )  and ("r" and ( not "s") )  )  and "t" )  and "u" )  and ("v" and "w" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Aromatic amine AND Aryl AND Benzyl by Organic Functional groups

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Aromatic amine AND Aryl AND Benzyl AND Overlapping groups by Organic Functional groups (nested)

Domain logical expression index: "c"

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

Domain logical expression index: "d"

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

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.4

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Nucleophilic addition reaction with cycloisomerization OR AN2 >> Nucleophilic addition reaction with cycloisomerization >> Hydrazine Derivatives 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 after aldehyde release OR AN2 >> Shiff base formation after aldehyde release >> Specific Acetate Esters OR Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> Acridone, Thioxanthone, Xanthone and Phenazine Derivatives OR Non-covalent interaction >> DNA intercalation >> Coumarins OR Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide and Aminoalkylamine Side Chain OR Non-covalent interaction >> DNA intercalation >> Fused-Ring Primary Aromatic Amines OR Non-covalent interaction >> DNA intercalation >> Quinolone Derivatives OR Radical OR Radical >> Generation of ROS by glutathione depletion (indirect) OR Radical >> Generation of ROS by glutathione depletion (indirect) >> Haloalkanes Containing Heteroatom OR Radical >> Radical mechanism by ROS formation OR Radical >> Radical mechanism by ROS formation >> Five-Membered Aromatic Nitroheterocycles OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Acridone, Thioxanthone, Xanthone and Phenazine Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> C-Nitroso Compounds OR Radical >> Radical mechanism via ROS formation (indirect) >> Conjugated Nitro Compounds OR Radical >> Radical mechanism via ROS formation (indirect) >> Coumarins OR Radical >> Radical mechanism via ROS formation (indirect) >> Fused-Ring Primary Aromatic Amines OR Radical >> Radical mechanism via ROS formation (indirect) >> Geminal Polyhaloalkane Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> Hydrazine Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitro Azoarenes OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitroaniline Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> Polynitroarenes OR Radical >> Radical mechanism via ROS formation (indirect) >> p-Substituted Mononitrobenzenes OR Radical >> Radical mechanism via ROS formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines OR Radical >> ROS formation after GSH depletion (indirect) OR Radical >> ROS formation after GSH depletion (indirect) >> Haloalcohols OR SN1 OR SN1 >> Nucleophilic attack after carbenium ion formation OR SN1 >> Nucleophilic attack after carbenium ion formation >> Specific Acetate Esters OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Fused-Ring Primary Aromatic Amines OR SN1 >> Nucleophilic attack after nitrenium ion formation OR SN1 >> Nucleophilic attack after nitrenium ion formation >> Single-Ring Substituted Primary Aromatic Amines OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Conjugated Nitro Compounds OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitro Azoarenes OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitroaniline Derivatives OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Polynitroarenes OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> p-Substituted Mononitrobenzenes OR SN1 >> Nucleophilic substitution after glutathione-induced nitrenium ion formation OR SN1 >> Nucleophilic substitution after glutathione-induced nitrenium ion formation >> C-Nitroso Compounds OR SN2 OR SN2 >> Acylation OR SN2 >> Acylation >> Specific Acetate Esters 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 >> Haloalcohols OR SN2 >> Alkylation, direct acting epoxides and related OR SN2 >> Alkylation, direct acting epoxides and related >> Epoxides and Aziridines OR SN2 >> Alkylation, direct acting epoxides and related after cyclization OR SN2 >> Alkylation, direct acting epoxides and related after cyclization >> Nitrogen and Sulfur Mustards OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom >> Haloalkanes Containing Heteroatom OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom >> Sulfonates and Sulfates OR SN2 >> Direct acting epoxides formed after metabolic activation OR SN2 >> Direct acting epoxides formed after metabolic activation >> Coumarins OR SN2 >> Direct acting epoxides formed after metabolic activation >> Quinoline Derivatives OR SN2 >> Direct nucleophilic attack on diazonium cation OR SN2 >> Direct nucleophilic attack on diazonium cation >> Hydrazine Derivatives 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 >> 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 OR SN2 >> SN2 at an activated carbon atom OR SN2 >> SN2 at an activated carbon atom >> Quinoline Derivatives by DNA binding by OASIS v.1.4

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Michael addition AND Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals AND Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Arenes AND SN1 AND SN1 >> Nitrenium Ion formation AND SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine by DNA binding by OECD

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Michael addition >> P450 Mediated Activation of Heterocyclic Ring Systems OR Michael addition >> P450 Mediated Activation of Heterocyclic Ring Systems >> Thiophenes-Michael addition OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> 5-alkoxyindoles OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Hydroquinones OR No alert found OR SN1 >> Iminium Ion Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines OR SN1 >> Nitrenium Ion formation >> Aromatic azo OR SN1 >> Nitrenium Ion formation >> Aromatic nitro OR SN1 >> Nitrenium Ion formation >> Primary (unsaturated) heterocyclic amine OR SN1 >> Nitrenium Ion formation >> Primary aromatic amine OR SN1 >> Nitrenium Ion formation >> Secondary (unsaturated) heterocyclic amine OR SN1 >> Nitrenium Ion formation >> Secondary aromatic amine OR SN1 >> Nitrenium Ion formation >> Unsaturated heterocyclic azo OR SN2 OR SN2 >> P450 Mediated Epoxidation OR SN2 >> P450 Mediated Epoxidation >> Thiophenes-SN2 by DNA binding by OECD

Domain logical expression index: "i"

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

Domain logical expression index: "j"

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 by Estrogen Receptor Binding

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 Non-Metals by Groups of elements

Domain logical expression index: "m"

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

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Not categorized by US-EPA New Chemical Categories

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Aldehydes (Acute toxicity) OR Aliphatic Amines OR Esters (Acute toxicity) OR Neutral Organics by US-EPA New Chemical Categories

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as No alert found by Protein binding alerts for Chromosomal aberration by OASIS v.1.2

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Ester aminolysis or thiolysis OR Acylation >> Ester aminolysis or thiolysis >> Carbamates OR AN2 OR AN2 >> Michael addition to the quinoid type structures OR AN2 >> Michael addition to the quinoid type structures >> N-Subsituted Aromatic Amines by Protein binding alerts for Chromosomal aberration by OASIS v.1.2

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as No alert found by Protein binding alerts for skin sensitization by OASIS v1.4

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as 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 sulfur atom OR SN2 >> SN2 reaction at a sulfur atom >> Thiocyanates by Protein binding alerts for skin sensitization by OASIS v1.4

Domain logical expression index: "t"

Similarity boundary:Target: CCN(Cc1ccccc1)c1ccccc1
Threshold=50%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "u"

Similarity boundary:Target: CCN(Cc1ccccc1)c1ccccc1
Threshold=60%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "v"

Parametric boundary:The target chemical should have a value of log Kow which is >= 2.52

Domain logical expression index: "w"

Parametric boundary:The target chemical should have a value of log Kow which is <= 4.25

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The LD50 was estimated to be 1042.3 mg/kg bw when rats were orally exposed with N-benzyl-N-ethylaniline. 

Executive summary:

In a prediction done by SSS (2017) using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor, the acute oral toxicity was estimated for N-benzyl-N-ethylaniline. The LD50 was estimated to be 1042.3 mg/kg bw when rats were orally exposed with N-benzyl-N-ethylaniline. 

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

1 042.3 mg/kg bw

Quality of whole database:

Data is from K2 prediction model

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Acute oral toxicity:

Prediction model based estimation and data from read across chemicals have been reviewed to determine the oral toxic nature of

N-benzyl-N-ethylaniline upon single exposure by oral route. The studies are as mentioned below:

In a prediction done by SSS (2017) using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor, the acute oral toxicity was estimated for N-benzyl-N-ethylaniline. The LD50 was estimated to be 1042.3 mg/kg bw when rats were orally exposed with N-benzyl-N-ethylaniline. 

In an acute oral toxicity estimation was done by using Danish QSAR, 50 % mortality observed at 800 mg/kg bw in mice. Therefore, LD50 was estimated to be 800 mg/kg bw when mice were treated with N-benzyl-N-ethylaniline orally.  

Acute toxicity test was performed for Ethylbenzylaniline to 10 mice at 2% concentration during 5 day test of repellency. The animals were fed 25 white wheat seeds treated with 2.0% of the target chemical. The test results, designated as REP, were summarized by the percentage of mice refusing to eat an average of 13 or more treated seeds per day during the 5-day test period. The repellency percentage for house mouse to Ethyl benzyl aniline (92-59-1) was considered to be 2.0 %.

In a study for 60 -70% structurally similar read across chemical, acute oral toxicity study was performed by Ellis et al (Journal of Pharmaceutical Sciences, 1980) to determine the oral toxic nature of Tripelennamine hydrochloride (RA CAS no 154 -69 -8). The study was performed using TAC: SD/N fBr or Charles River CD/SD male rats. The test chemical was dissolved in 0.5% methylcellulose or carboxymethylcellulose sodium and dosed to 5-10 animals in graded doses orally. The animals were then housed in their cages with food and water ad libitum and all deaths occurring within 14 days was recorded.The acute oral median lethal dose (LD50) for Tripelennamine hydrochloride is considered to be 469 mg/Kg with a 95% confidence interval of 285-687 mg/Kg.

Another study was also performed (Environmantal Protection Agency, 1986) to determine the acute oral toxic nature of 60 -70% structurally similar read across chemical N-(2-Chloroethyl) - N- Ethylaniline (RA CAS no 92 -49 -9, IUPAC name: N-(2-Chloroethyl)-N-Ethylaniline). The study was performed using male albino rats of Sprague Dawley strain. The animals were fasted overnight and the doses were given orally by gavage route at dose levels of0.050, 0.10, 0.2, 0.4, 0.8, 1.6 mL/Kg be (54.5, 109, 218, 436, 872 or 1744 mg/kg bw). The animals were observed following dosing and during the 14 days observation period. The surviving animals were weighed at the end of observation period. At the end of 14 days observation period, the animals were subjected to gross pathology. All animals receiving 872 and 1744 mg/Kg bw dose died during the study period.Dead animals showed diarrhea, hyperemia of gastro intestinal tract and bloody discharge around eyes. Organs of thorax and abdomen were normal in surviving rats. On the basis of observations made, the acute oral median lethal dose (LD50) forN-(2-Chloroethyl)-N-Ethylaniline is considered to be 616 mg/Kg bw with a 95% confidence interval of 305- 1232 mg/Kg bw.

Based on the data available for the target chemical and data from read across, N-benzyl-N-ethylaniline classifies into "Acute tox Category 4" as per the criteria mentioned in CLP regulation.