N-[3-(diethylamino)phenyl]acetamide

Endpoint summary

Description of key information

Acute toxicity: oral

The acute toxicity study was predicted using OECD QSAR toolbox version 3.3 (2017); to evaluate the toxic effects of administration of N-[3-(diethylamino)ph enyl]acetamide (CAS No. 6375-46-8) in mouse by the oral route. 50% mortality was observed. The acute oral median lethal dose (LD50) of N-[3-(diethylamino) phenyl]acetamide in mouse was estimated to be 3306.05 mg/kg b.wt. Thus by considering the CLP criteria for acute toxicity rating for the chemicals, it infers that N-[3-(diethylamino)phenyl]acetamide (CAS No. 6375-46-8) does not exhibit acute toxicity via the oral route.

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:

Prediction is done using OECD QSAR toolbox version 3.3 and the supporting QMRF report has been attached.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Principles of method if other than guideline:

Prediction is done using OECD QSAR Toolbox version 3.3

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

mouse

Strain:

other: Tif MAG

Sex:

male/female

Route of administration:

oral: unspecified

Vehicle:

not specified

Details on oral exposure:

No data available

Doses:

No data available

No. of animals per sex per dose:

No data available

Control animals:

not specified

Details on study design:

No data available

Statistics:

No data available

Sex:

male/female

Dose descriptor:

LD50

Effect level:

3 306.05 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 50 % mortality observed

Mortality:

50% mortality was observed.

Clinical signs:

other: No data available

Gross pathology:

No data available

Other findings:

No data available

The prediction was based on dataset comprised from the following descriptors: LD50
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 ("g" and ( not "h") )  )  and ("i" and "j" )  )

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 SN1 AND SN1 >> Nitrenium Ion formation AND SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine 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 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 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 >> Unsaturated heterocyclic azo OR SN2 OR SN2 >> Direct Acting Epoxides and related OR SN2 >> Direct Acting Epoxides and related >> Epoxides OR SN2 >> Episulfonium Ion Formation OR SN2 >> Episulfonium Ion Formation >> Mustards OR SN2 >> SN2 at an sp3 Carbon atom OR SN2 >> SN2 at an sp3 Carbon atom >> Aliphatic halides by DNA binding by OECD

Domain logical expression index: "f"

Similarity boundary:Target: CCN(CC)c1cccc(NC(C)=O)c1
Threshold=40%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Not categorized by Repeated dose (HESS)

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Anilines (Hemolytic anemia with methemoglobinemia) Rank A OR Anilines (Hepatotoxicity) Rank C by Repeated dose (HESS)

Domain logical expression index: "i"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.647

Domain logical expression index: "j"

Parametric boundary:The target chemical should have a value of log Kow which is <= 3.37

Interpretation of results:

other: not classified based on CLP criteria

Conclusions:

The acute toxicity study was predicted using OECD QSAR toolbox version 3.3 (2017); to evaluate the toxic effects of administration of N-[3-(diethylamino)phenyl]acetamide (CAS No. 6375-46-8) in mouse by the oral route. 50% mortality was observed. Thus, the acute oral median lethal dose (LD50) of N-[3-(diethylamino)phenyl]acetamide in mouse was estimated to be 3306.05 mg/kg b.wt.

Executive summary:

The acute toxicity study was predicted using OECD QSAR toolbox version 3.3 (2017); to evaluate the toxic effects of administration of N-[3-(diethylamino)ph enyl]acetamide (CAS No. 6375-46-8) in mouse by the oral route. 50% mortality was observed. The acute oral median lethal dose (LD50) of N-[3-(diethylamino) phenyl]acetamide in mouse was estimated to be 3306.05 mg/kg b.wt. Thus by considering the CLP criteria for acute toxicity rating for the chemicals, it infers that N-[3-(diethylamino)phenyl]acetamide (CAS No. 6375-46-8) does not exhibit acute toxicity via the oral route.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

3 306.05 mg/kg bw

Quality of whole database:

The data is K2 level as the study has been obtained from prediction report done by using the OECD QSAR toolbox version 3.3.

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 toxicity: oral

Various studies including predicted results from the validated model and experimental study has been investigated for acute oral toxicity to a greater or lesser extent for the test chemical N-[3-(diethylamino)ph enyl]acetamide (CAS No. 6375-46-8) along with its structurally similar read across substances disodium 4,4'-bis[[6-anilino-4-[(2-hydroxyethyl)methylamino]-1,3,5-triazin-2-yl]amino]stilbene-2,2'-disulphonate (CAS No. 13863-31-5) and disodium 4,4'-bis[(4-anilino-6-morpholino-1,3,5-triazin-2-yl)amino]s tilbene-2, 2'-disulphonate (CAS No. 16090 -02 -1). The predicted data for target chemical N-[3-(diethylamino)phenyl]acetamide (CAS No. 6375-46-8) has been compared with experimental data (in vivo experiments in rodents i.e. most commonly in rats) for read across substance which are summarized as below:

 

The acute toxicity study was predicted using OECD QSAR toolbox version 3.3 (2017); to evaluate the toxic effects of administration of N-[3-(diethylamino)phenyl] acetamide (CAS No. 6375-46-8) in mouse by the oral route. 50% mortality was observed. Thus, the acute oral median lethal dose (LD50) of N-[3-(diethylamino) phenyl]acetamide in mouse was estimated to be 3306.05 mg/kg b.wt.

 

The above study is supported by the study based on the QSAR prediction done using the Danish (Q)SAR Database, in which the acute toxicity study was estimated to evaluate the toxic effects of administration of N-[3-(diethylamino)phenyl]acetamide (CAS No. 6375-46-8) in rat by the oral route. 50% mortality was observed. The acute oral median lethal dose (LD50) of N-[3-(diethylamino)phenyl]acetamide in rat was estimated to be 2800 mg/kg/day.

 

This is further supported by the experimental acute toxicity study done by Alan W. Burg et.al (C R C Critical Reviews in Environmental Control, 7:1, 91-120, 1977.) to evaluate the toxic effects of administration of Disodium 4,4'-bis[[6 -anilino-4-[(2-hydroxyethyl)methylamino]-1,3,5 -triazin-2-yl]amino]stilbene-2,2'-disulphonate (CAS No. 13863-31-5) in rat by the oral route. 50% mortality was observed. The acute oral median lethal dose (LD50) of Disodium 4,4'-bis[[6-anilino-4-[(2-hydroxyethyl)methylamino]-1,3,5-triazin-2-yl]amino] stilbene-2,2'-disulphonate in rat was observed to be >10000 mg/kg b.wt.

 

Moreover, the acute toxicity study conducted by Alan W. Burg et.al (C R C Critical Reviews in Environmental Control, 7:1, 91-120, 1977.) was to evaluate the toxic effects of administration of Disodium 4,4'-bis[(4-anilino-6-morpholino-1,3,5-triazin-2-yl)amino] stilb ene-2,2'-disulphonate (CAS No. 16090 -02-) in rat by the oral route. 50% mortality was observed. The acute oral median lethal dose (LD50) of Disodium 4,4'-bis[(4-anilino-6-morpholino-1,3,5- triazin-2-yl) amino]stilbene-2,2'-disulphonate in rat was observed to be >8000 mg/kg b.wt.

 

So, based on the above mentioned studies for target substance N-[3-(diethylamino)phenyl]acetamide (CAS No. 6375-46-8) and to its read across substance, the median lethal dose (LD50) value was found to be in the range of 2800 mg/kg bw to >10000 mg/kg b.wt. Thus, by comparing these studies with the criteria of CLP regulation, it infers that the test substance N-[3-(diethylamino)ph enyl]acetamide (CAS No. 6375-46-8) does not classify as an acute oral toxicant.

Justification for classification or non-classification

Based on the above mentioned studies for target substance N-[3-(diethylamino)ph enyl]acetamide (CAS No. 6375-46-8) and to its read across substance, it can be found that LD50 value is greater than 2000 mg/kg b.wt. Thus, by comparing these studies with the criteria of CLP regulation, it infers that the test substance N-[3-(diethylamino)phenyl]acetamide (CAS No. 6375-46-8) does not classify as an acute oral toxicant.