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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Endpoint:
toxicity to reproduction
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

Data source

Reference
Reference Type:
other: Predicted data
Title:
[R]: 631 mg/kg bw/day (actual dose received); Estimation for NOAEL for CAS 56765-79-8
Author:
Sustainability Support Services (Europe) AB
Year:
2017
Bibliographic source:
OECD QSAR Toolbox prediction Ver. 3.3; using categorisation and read across approach considering nearest 5 substances with Log Kow as the descriptor

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
other: as below
Principles of method if other than guideline:
Prediction is done using QSAR Toolbox version 3.3
GLP compliance:
not specified
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
3,4-dicyanoaniline
EC Number:
260-370-6
EC Name:
3,4-dicyanoaniline
Cas Number:
56765-79-8
Molecular formula:
C8H5N3
IUPAC Name:
4-aminobenzene-1,2-dicarbonitrile
Details on test material:
Name: 4-aminobenzene-1,2-dicarbonitrile
SMILES:Nc1ccc(C#N)c(C#N)c1
InChI: 1S/C8H5N3/c9-4-6-1-2-8(11)3-7(6)5-10/h1-3H,11H2
Mol. formula: C8H5N3
Molecular Weight: 143.148 g/mole
Specific details on test material used for the study:
Name: 4-aminobenzene-1,2-dicarbonitrile
SMILES:Nc1ccc(C#N)c(C#N)c1
InChI: 1S/C8H5N3/c9-4-6-1-2-8(11)3-7(6)5-10/h1-3H,11H2
Mol. formula: C8H5N3
Molecular Weight: 143.148 g/mole

Test animals

Species:
rat
Strain:
other: Crl:CD(SD)IGS BR VAF/Plus
Sex:
male/female

Administration / exposure

Route of administration:
oral: gavage
Type of inhalation exposure (if applicable):
not specified
Vehicle:
CMC (carboxymethyl cellulose)
Details on exposure:
not specified
Details on mating procedure:
not specified
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
63 days
Frequency of treatment:
Daily
Details on study schedule:
not specified
Doses / concentrations
Remarks:
Not specified
No. of animals per sex per dose:
25 males and 25 females
Control animals:
yes, concurrent vehicle
Details on study design:
not specified
Positive control:
not specified

Examinations

Parental animals: Observations and examinations:
not specified
Oestrous cyclicity (parental animals):
not specified
Sperm parameters (parental animals):
not specified
Litter observations:
not specified
Postmortem examinations (parental animals):
not specified
Postmortem examinations (offspring):
not specified
Statistics:
not specified
Reproductive indices:
not specified
Offspring viability indices:
not specified

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:
not specified
Dermal irritation (if dermal study):
not specified
Mortality:
not specified
Body weight and weight changes:
not specified
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Immunological findings:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
not specified
Other effects:
not specified

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:
not specified
Reproductive function: sperm measures:
not specified
Reproductive performance:
not specified

Effect levels (P0)

Dose descriptor:
NOAEL
Effect level:
630.5 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
histopathology: non-neoplastic
other: No effect observed

Target system / organ toxicity (P0)

Critical effects observed:
not specified
System:
other: not specified
Organ:
not specified
Treatment related:
not specified
Dose response relationship:
not specified
Relevant for humans:
not specified

Results: F1 generation

General toxicity (F1)

Clinical signs:
not specified
Dermal irritation (if dermal study):
not specified
Mortality / viability:
no mortality observed
Body weight and weight changes:
not specified
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Sexual maturation:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Histopathological findings:
not specified
Other effects:
not specified

Developmental neurotoxicity (F1)

Behaviour (functional findings):
not specified

Developmental immunotoxicity (F1)

Developmental immunotoxicity:
not specified

Effect levels (F1)

Dose descriptor:
other: not specified
Generation:
other: not specified
Based on:
not specified
Sex:
not specified
Basis for effect level:
other: not specified
Remarks on result:
other: not specified

Target system / organ toxicity (F1)

Critical effects observed:
not specified
System:
other: not specified
Organ:
not specified
Treatment related:
not specified
Dose response relationship:
not specified
Relevant for humans:
not specified

Overall reproductive toxicity

Reproductive effects observed:
not specified
Treatment related:
not specified
Relation to other toxic effects:
not specified
Dose response relationship:
not specified
Relevant for humans:
not specified

Any other information on results incl. tables

The prediction was based on dataset comprised from the following descriptors: NOAEL
Estimation method: Takes average value from the 5 nearest neighbours
Domain  logical expression:Result: In Domain

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

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

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Weak binder, NH2 group by Estrogen Receptor Binding

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Phenols and Anilines by Acute aquatic toxicity MOA by OASIS

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Anilines (Unhindered) AND Phthalonitriles by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.3

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >>  Michael-type addition, quinoid structures OR AN2 >>  Michael-type addition, quinoid structures >> Quinones OR Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> Amino Anthraquinones OR Non-covalent interaction >> DNA intercalation >> Fused-Ring Primary Aromatic Amines OR Non-covalent interaction >> DNA intercalation >> Quinones OR Radical OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Amino Anthraquinones OR Radical >> Radical mechanism via ROS formation (indirect) >> Fused-Ring Primary Aromatic Amines OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitroaniline Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> Quinones 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 >> Amino Anthraquinones OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Fused-Ring Primary Aromatic Amines OR SN1 >> Nucleophilic attack after metabolic 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 >> Nitroaniline Derivatives by DNA binding by OASIS v.1.3

Domain logical expression index: "h"

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

Domain logical expression index: "i"

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: "j"

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: "k"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Michael-type addition to quinoid structures OR AN2 >> Michael-type addition to quinoid structures >> Phenols by Protein binding alerts for Chromosomal aberration by OASIS v1.1

Domain logical expression index: "l"

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

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Aniline AND Aryl AND Nitrile by Organic Functional groups

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Aldimine OR Aliphatic Amine, primary OR Alkane, branched with tertiary carbon by Organic Functional groups

Domain logical expression index: "o"

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

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as 3-Methylcholantrene (Hepatotoxicity) Alert by Repeated dose (HESS)

Domain logical expression index: "q"

Parametric boundary:The target chemical should have a value of log Kow which is >= -2.09

Domain logical expression index: "r"

Parametric boundary:The target chemical should have a value of log Kow which is <= 3.53

Applicant's summary and conclusion

Conclusions:
The NOAEL was estimated to be 630.5 mg/kg bw when rats were orally exposed with 4-aminobenzene-1,2-dicarbonitrile.
Executive summary:

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the reproductive toxicity was estimated for 4-aminobenzene-1,2-dicarbonitrile. The NOAEL was estimated to be 630.5 mg/kg bw when rats were orally exposed with 4-aminobenzene-1,2-dicarbonitrile.