(3-aminophenyl)urea

Endpoint summary

Description of key information

LD50 was estimated to be 3055 mg/kg bw when Wistar female rats were orally exposed with 1-(3-aminophenyl)urea.

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 predicted using OECD QSAR toolbox version 3.3 and the supporting QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: estimation

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.3

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 (as cited in study report): 1-(3-aminophenyl)urea
- Molecular formula: C7H9N3O
- Molecular weight: 151.168 g/mole
- Substance type: Organic
- Physical state: Solid

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

No data available

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

No data available

Doses:

3055 mg/kg bw

No. of animals per sex per dose:

20 female rats

Control animals:

no

Details on study design:

No data available

Statistics:

No data available

Preliminary study:

No data available

Sex:

female

Dose descriptor:

LD50

Effect level:

3 055 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 50 % mortality observed

Mortality:

No data available

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 7 nearest neighbours
Domain  logical expression:Result: In Domain

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

Domain logical expression index: "a"

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

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Radical AND Radical >> Radical mechanism via ROS formation (indirect) AND Radical >> Radical mechanism via ROS formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines AND SN1 AND SN1 >> Nucleophilic attack after metabolic nitrenium ion formation AND SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Single-Ring Substituted Primary Aromatic Amines by DNA binding by OASIS v.1.3

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as SN1 OR SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >> Aromatic phenylureas OR SN1 >> Nitrenium Ion formation >> Primary aromatic amine by DNA binding by OECD ONLY

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 >> Aromatic phenylureas AND SN1 >> Nitrenium Ion formation >> Primary aromatic amine by DNA binding by OECD ONLY

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as No alert found by Protein binding alerts for Chromosomal aberration by OASIS v1.1

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Ac-SN2 OR Ac-SN2 >> Acylation involving an activated (glucuronidated) carboxamide group OR Ac-SN2 >> Acylation involving an activated (glucuronidated) carboxamide group >> Carboxylic Acid Amines OR Ac-SN2 >> Direct acylation involving a leaving group OR Ac-SN2 >> Direct acylation involving a leaving group >> Carboxylic Acid Amines OR AN2 OR AN2 >> Michael addition to the quinoid type structures OR AN2 >> Michael addition to the quinoid type structures >> N-Subsituted Aromatic Amines OR AN2 >> Michael addition to the quinoid type structures >> Substituted Anilines OR AN2 >> Michael-type addition to quinoid structures OR AN2 >> Michael-type addition to quinoid structures >> Carboxylic Acid Amines OR AN2 >> Michael-type addition to quinoid structures >> Phenols by Protein binding alerts for Chromosomal aberration by OASIS v1.1

Domain logical expression index: "g"

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

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Ester aminolysis OR Acylation >> Ester aminolysis >> Amides OR SN2 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 alerts for skin sensitization by OASIS v1.3

Domain logical expression index: "i"

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

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Non-Metals by Groups of elements

Domain logical expression index: "k"

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

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as No alert found by rtER Expert System ver.1 - USEPA

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as 4-Alkylanilines by rtER Expert System ver.1 - USEPA

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as No alert found by DNA alerts for AMES, MN and CA by OASIS v.1.3

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Radical OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines OR SN1 OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Single-Ring Substituted Primary Aromatic Amines by DNA alerts for AMES, MN and CA by OASIS v.1.3

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Not known precedent reproductive and developmental toxic potential by DART scheme v.1.0

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Known precedent reproductive and developmental toxic potential OR Toluene and small alkyl toluene derivatives (8a) by DART scheme v.1.0

Domain logical expression index: "r"

Parametric boundary:The target chemical should have a value of log Kow which is >= -3.69

Domain logical expression index: "s"

Parametric boundary:The target chemical should have a value of log Kow which is <= 2.11

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

LD50 was estimated to be 3055 mg/kg bw when Wistar female rats were orally exposed with 1-(3-aminophenyl)urea.

Executive summary:

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute oral toxicity was estimated for 1-(3-aminophenyl)urea. The LD50 was estimated to be 3055 mg/kg bw when Wistar female rats were orally exposed with 1-(3-aminophenyl)urea.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

3 055 mg/kg bw

Quality of whole database:

Data is Klimisch 2 and from OECD QSAR toolbox

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:

In different studies, 4-methylphenyl acetate has been investigated for acute oral toxicity to a greater or lesser extent. Often are the studies based on in vivo experiments in rodents, i.e. most commonly in rats for 4-methylphenyl acetate along with the study available on structurally similar read across substance Phenyl acetate (CAS: 122-79-2). The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies.

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute oral toxicity was estimated for 1-(3-aminophenyl)urea. The LD50 was estimated to be 3055 mg/kg bw when Wistar female rats were orally exposed with 1-(3-aminophenyl)urea.

In another experimental study given by U. S. National Library of Medicine (HSDB (Hazardous Substances Data Bank); US national Library of Medicine reviewed by SRC, 2017) on structurally similar read across substance Urea (CAS no 57-13-6), rats were treated with Urea orally. 50 % mortality observed was observed in treated rats at 8471 mg/kg bw. Therefore, LD50 was considered to be mg/kg bw when rats were treated with Urea.

Thus, based on the above studies and predictions on 1-(3-aminophenyl)urea and its read across substances, it can be concluded that LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, 1-(3-aminophenyl)urea can be Not classified for acute oral toxicity.

Justification for classification or non-classification

Based on the above studies and predictions on 1-(3-aminophenyl)urea and its read across substances, it can be concluded that LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, 1-(3-aminophenyl)urea can be Not classified for acute oral toxicity.