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Diss Factsheets

Administrative data

Description of key information

LD50 was estimated to be 2884 mg/kg bw when Wistar female rats were orally exposed with (4-(4-aminophenyl)(4-iminocyclohexa-2,5-dienylidene)methyl)-2-methylaniline hydrochloride.

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: as below
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:
IUPAC name:((4-(4-aminophenyl)(4-iminocyclohexa-2,5-dienylidene)methyl)-2-methylaniline hydrochloride)
commen name : Basic violet 14
Molecular formula :C20H19N3.ClH
molecular weight: 337.8 g/mol
InChI:1S/C20H19N3.ClH/c1-13-12-16(6-11-19(13)23)20(14-2-7-17(21)8-3-14)15-4-9-18(22)10-5-15;/h2-12,21H,22-23H2,1H3;1H/b20-14-,21-17?
Smiles:C(\c1cc(c(N)cc1)C)(c1ccc(N)cc1)=C1/C=CC(=N)C=C1.Cl
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
not specified
Route of administration:
oral: gavage
Vehicle:
other: sesame oil
Details on oral exposure:
not specified
Doses:
2884 mg/kg bw
No. of animals per sex per dose:
10
Control animals:
not specified
Details on study design:
not specified
Statistics:
not specified
Preliminary study:
not specified
Sex:
female
Dose descriptor:
LD50
Effect level:
2 884 mg/kg bw
Based on:
test mat.
Remarks on result:
other: 50 % mortality observed
Mortality:
not specified
Clinical signs:
other: not specified
Gross pathology:
not specified
Other findings:
not specified

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" or "d" or "e" )  and "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 ("q" and ( not "r") )  )  and "s" )  and "t" )  and ("u" and ( not "v") )  )  and ("w" and ( not "x") )  )  and ("y" and ( not "z") )  )  and ("aa" and "ab" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Anilines (Acute toxicity) AND Dianilines AND Not categorized AND Triarylmethane Pigments/Dyes with Non-solubilizing Groups by US-EPA New Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Alkene OR Allyl OR Aniline OR Aryl OR Dianilines OR Ketimine OR No functional group found by Organic Functional groups ONLY

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Alkene OR Allyl OR Dianilines OR Ketimine OR No functional group found OR Overlapping groups by Organic Functional groups (nested) ONLY

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Aliphatic Carbon [CH] OR Aliphatic Carbon [-CH2-] OR Aliphatic Carbon [-CH3] OR Aliphatic Nitrogen, one aromatic attach [-N] OR Aromatic Carbon [C] OR No functional group found OR Olefinic carbon [=CH- or =C<] by Organic functional groups (US EPA) ONLY

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Amine OR Aromatic compound OR No functional group found OR Primary amine OR Primary aromatic amine by Organic functional groups, Norbert Haider (checkmol) ONLY

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as No alert found AND Non-specific AND Non-specific >> Incorporation into DNA/RNA, due to structural analogy with  nucleoside bases    AND Non-specific >> Incorporation into DNA/RNA, due to structural analogy with  nucleoside bases    >> Specific Imine and Thione Derivatives AND Radical AND Radical >> Radical mechanism via ROS formation (indirect) AND Radical >> Radical mechanism via ROS formation (indirect) >> Specific Imine and Thione Derivatives AND SN1 AND SN1 >> Nucleophilic substitution on diazonium ions AND SN1 >> Nucleophilic substitution on diazonium ions >> Specific Imine and Thione Derivatives by DNA binding by OASIS v.1.3 ONLY

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as No alert found AND SN1 AND SN1 >> Nitrenium Ion formation AND SN1 >> Nitrenium Ion formation >> Primary aromatic amine by DNA binding by OECD

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as 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 >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Polycyclic (PAHs) and heterocyclic (HACs) aromatic hydrocarbons-Michael addition OR Michael addition >> Polarised Alkenes-Michael addition OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated ketones OR SN2 OR SN2 >> SN2 at an sp3 Carbon atom OR SN2 >> SN2 at an sp3 Carbon atom >> Phosphonic esters by DNA binding by OECD

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Non binder, non cyclic structure AND Strong binder, NH2 group by Estrogen Receptor Binding

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Moderate binder, NH2 group OR Non binder, impaired OH or NH2 group OR Non binder, MW>500 OR Non binder, without OH or NH2 group OR Weak binder, NH2 group by Estrogen Receptor Binding

Domain logical expression index: "k"

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: "l"

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 Exclusion rules not met AND Group All Melting Point > 200 C AND Group CN Aqueous Solubility < 0.1 g/L AND Group CN Melting Point > 180 C AND Group CN Molecular Weight > 290 g/mol AND Group CN Vapour Pressure < 0.001 Pa by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Melting Point > 200 C OR (!Undefined)Group C Surface Tension > 62 mN/m OR (!Undefined)Group CN Melting Point > 180 C OR (!Undefined)Group CN Vapour Pressure < 0.001 Pa OR Group All log Kow < -3.1 OR Group All log Kow > 9 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 CHal log Kow > 4.5 OR Group CHal Melting Point > 65 C OR Group CHal Molecular Weight > 280 g/mol by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Aromatic amines AND Inclusion rules not met by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Organic silicon halides by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "p"

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

Domain logical expression index: "q"

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

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as Alkali Earth OR Alkaline Earth OR Metalloids OR Metals OR Rare Earth OR Transition Metals OR Unknown chemical element by Groups of elements

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as Alkene AND Allyl AND Aniline AND Aryl AND Dianilines AND Ketimine AND No functional group found by Organic Functional groups ONLY

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as Amine AND Aromatic compound AND No functional group found AND Primary amine AND Primary aromatic amine by Organic functional groups, Norbert Haider (checkmol) ONLY

Domain logical expression index: "u"

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

Domain logical expression index: "v"

Referential boundary: The target chemical should be classified as Aliphatic nitriles (Hepatotoxicity) Rank B by Repeated dose (HESS)

Domain logical expression index: "w"

Referential boundary: The target chemical should be classified as No alert found AND Primary aromatic amine, hydroxyl amine and its derived esters by in vivo mutagenicity (Micronucleus) alerts by ISS

Domain logical expression index: "x"

Referential boundary: The target chemical should be classified as H-acceptor-path3-H-acceptor by in vivo mutagenicity (Micronucleus) alerts by ISS

Domain logical expression index: "y"

Referential boundary: The target chemical should be classified as Inorganic chemical AND Not covered by current version of the decision tree AND Not known precedent reproductive and developmental toxic potential by DART scheme v.1.0

Domain logical expression index: "z"

Referential boundary: The target chemical should be classified as Di-substituted hydrocarbons (24a) OR Known precedent reproductive and developmental toxic potential by DART scheme v.1.0

Domain logical expression index: "aa"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.226

Domain logical expression index: "ab"

Parametric boundary:The target chemical should have a value of log Kow which is <= 4.26

Interpretation of results:
Category 5 based on GHS criteria
Conclusions:
LD50 was estimated to be 2884 mg/kg bw when Wistar female rats were orally exposed with (4-(4-aminophenyl)(4-iminocyclohexa-2,5-dienylidene)methyl)-2-methylaniline hydrochloride.
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 (4-(4-aminophenyl)(4-iminocyclohexa-2,5-dienylidene)methyl)-2-methylaniline hydrochloride. The LD50 was estimated to be 2884 mg/kg bw when Wistar female rats were orally exposed with (4-(4-aminophenyl)(4-iminocyclohexa-2,5-dienylidene)methyl)-2-methylaniline hydrochloride.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 884 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-(4-aminophenyl)(4-iminocyclohexa-2,5-dienylidene)methyl)-2-methylaniline hydrochloride has been investigated for acute oral toxicity to a greater or lesser extent. Often are the studies based on in vivo experiments and estimated data in rodents, i.e. most commonly in rats for (4-(4-aminophenyl)(4-iminocyclohexa-2,5-dienylidene)methyl)-2-methylaniline hydrochloride along with the study available on structurally similar read across substance4,4'-(4-iminocyclohexa-2,5-dienylidenemethylene) dianiline hydrochloride (CAs no 569-61-9) andSulfur (CAS no 7704-34-9). 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 (4-(4-aminophenyl)(4-iminocyclohexa-2,5-dienylidene)methyl)-2-methylaniline hydrochloride. The LD50 was estimated to be 2884 mg/kg bw when Wistar female rats were orally exposed with (4-(4-aminophenyl)(4-iminocyclohexa-2,5-dienylidene)methyl)-2-methylaniline hydrochloride.

In another experimental study given by European Commission (EC) - Scientific Committee on Cosmetology (SCC) (Commission of the European Communities, 1988), rat were treated with (4-(4-aminophenyl)(4-iminocyclohexa-2,5-dienylidene)methyl)-2-methylaniline hydrochloride at the concentration of 12000 mg/kg bw orally as a 40% suspension in carboxymethylcellulose.No mortality was observed at 12000 mg/kg bw in treated rats. Therefore, LD50 was considered to be > 12000 mg/kg when rats were treated with 4-(4-aminophenyl)(4-iminocyclohexa-2,5-dienylidene)methyl)-2-methylaniline hydrochloride) orally.

Further supported by experimental study conducted by Sasaki et al (Mutation Research, Genetic Toxicology and Environmental Mutagenesis (1999), 444(1), 249-255), ddY male mice were treated with ((4-(4-aminophenyl)(4-iminocyclohexa-2,5-dienylidene)methyl)-2-methylaniline hydrochloride (Magenta) in the concentration of 2000 mg/kg bw orally by gavage and observed for 24 hours. 50% mortality observed was observed in treated mice at 2000 mg/kg bw. No gross pathological changes were observed in treated mice. No tumors and DNA damage was observed in treated mice. Therefore, LD50 was considered to be 2000 mg/kg bw ddY male mice were treated with ((4-(4-aminophenyl)(4-iminocyclohexa-2,5-dienylidene)methyl)-2-methylaniline hydrochloride (Magenta) orally by gavage.

The above mention study is mainly based on genotoxicity and animals were treated with Maximum tolerated dose set at about half the LD50. This means the animals treated with the dose which is half the LD50. Hence, considered as not toxic.

This is supported by experimental study given by U.S. National Library of Medicine (ChemIDplus, A TOXNET DATABASE, Lite Browse Advanced, 2017)on structurally similar read across substance4,4'-(4-iminocyclohexa-2,5-dienylidenemethylene) dianiline hydrochloride (CAs no 569-61-9),mousewere treated with 4,4'-(4-iminocyclohexa-2,5-dienylidenemethylene)dianiline hydrochloride at the concentration of5000 mg/kg. 50% morality was observed inmouseat5000 mg/kg. Hence,LD50 was considered to be5000mg/kg bw as 50% morality was observed, whenmousewas treated with 4,4'-(4-iminocyclohexa-2,5-dienylidenemethylene) dianiline hydrochloride orally.

Again this is supported byexperimental study given byEuropean Commission (IUCLID Dataset, European Commission – European Chemicals Bureau, 19 – FEB - 2000)on structurally similar read across substance Sulfur (CAS no 7704-34-9), male Wistar rats were treated with Sulfurat the concentration of0, 500, 1000, 2500 and 5000 mg/kg bw.The test substance (sulphur) was dissolved in aqueous emulsion and administered by oral gavage route. Animals were observed for clinical signs and mortality.No mortality was observed. Clinical signs noted such as breathing difficulties at doses of 1000, 2500 and 5000 mg/kg. Therefore,LD50 was considered to be> 5000 mg/kg bw,when male Wistar rats were treated withSulfurby oral gavage route.

Thus based on the above predictions and studies on (4-(4-aminophenyl)(4-iminocyclohexa-2,5-dienylidene)methyl)-2-methylaniline hydrochloride 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, (4-(4-aminophenyl)(4-iminocyclohexa-2,5-dienylidene)methyl)-2-methylaniline hydrochloride can be not classified for acute oral toxicity. 

Justification for classification or non-classification

Based on the above predictions and studies on (4-(4-aminophenyl)(4-iminocyclohexa-2,5-dienylidene)methyl)-2-methylaniline hydrochloride 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, (4-(4-aminophenyl)(4-iminocyclohexa-2,5-dienylidene)methyl)-2-methylaniline hydrochloride can be not classified for acute oral toxicity.