Registration Dossier

Administrative data

Description of key information

Acute oral toxicity

LD50 was estimated to be 711mg/kg bw, when male Fischer 344 rat were exposed with N-(4-{bis[4-(dimethylamino)phenyl]methylene}cyclohexa-2,5-dien-1-ylidene)-N-methylmethanaminium chloride (548-62-9) orally.

Acute inhalation toxicity

Gentian violet has a very low vapor pressure (2.57 X 10-12 Pa), so the potential for the generation of inhalable vapours is very low, also the normal conditions of use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be highly unlikely and therefore this end point was considered for waiver

Acute dermal toxicity

LD50 was estimated to be 6869.69mg/kg bw, when male and female New Zealand White rabbits were exposed with N-(4-{bis[4-(dimethylamino)phenyl]methylene}cyclohexa-2,5-dien-1-ylidene)-N-methylmethanaminium chloride (548-62-9) by dermal application.

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 v3.3 and the QMRF report has been attached.
Qualifier:
equivalent or similar to
Guideline:
other: As mentioned below
Principles of method if other than guideline:
Prediction was done using OECD QSAR toolbox v3.3, 2017
GLP compliance:
not specified
Test type:
other: not specified
Limit test:
no
Specific details on test material used for the study:
Name of test material (as cited in study report): Crystal violet
- IUPAC name: N-(4-{bis[4-(dimethylamino)phenyl]methylene}cyclohexa-2,5-dien-1-ylidene)-N-methylmethanaminium chloride
- Molecular formula : C25H30N3.Cl
Molecular weight : 407.986 g/mol
- Smiles notation: C(\c1ccc(N(C)C)cc1)(c1ccc(N(C)C)cc1)=C1\C=C\C(=[N+](/C)C)C=C1.[ClH-]
- InChl:1S/C25H30N3.ClH/c1-26(2)22-13-7-19(8-14-22)25(20-9-15-23(16-10-20)27(3)4)21-11-17-24(18-12-21)28(5)6;/h7-18H,1-6H3;1H/q+1;/p-1
- Substance type: Organic
- Physical state: Solid
Species:
rat
Strain:
Fischer 344
Sex:
male
Details on test animals and environmental conditions:
No data available
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
No data available
Doses:
711 mg/kg bw
No. of animals per sex per dose:
3
Control animals:
not specified
Details on study design:
No data available
Statistics:
No data available
Preliminary study:
No data available
Sex:
male
Dose descriptor:
LD50
Effect level:
711 mg/kg bw
Based on:
test mat.
Remarks on result:
other: 50% mortality was observed
Mortality:
No data available
Clinical signs:
No data available
Body weight:
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" or "d" )  and ("e" and ( not "f") )  )  and "g" )  and ("h" and ( not "i") )  )  and "j" )  and "k" )  and "l" )  and "m" )  and ("n" and ( not "o") )  )  and "p" )  and "q" )  and ("r" and ( not "s") )  )  and ("t" and "u" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Alkene OR Ammonium salt OR Aromatic amine OR Aryl by Organic Functional groups ONLY

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Alkene OR Ammonium salt OR Aromatic amine OR Overlapping groups by Organic Functional groups (nested) ONLY

Domain logical expression index: "c"

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 Amino, aliphatic attach [-N<] OR Aromatic Carbon [C] OR Olefinic carbon [=CH- or =C<] by Organic functional groups (US EPA) ONLY

Domain logical expression index: "d"

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

Domain logical expression index: "e"

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

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Non binder, impaired OH or NH2 group OR Non binder, MW>500 OR Non binder, non cyclic structure OR Weak binder, NH2 group by Estrogen Receptor Binding

Domain logical expression index: "g"

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

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Group 14 - Carbon C AND Group 15 - Nitrogen N AND Group 17 - Halogens Cl AND Group 17 - Halogens F,Cl,Br,I,At by Chemical elements

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Group 1 - Alkali Earth Li,Na,K,Rb,Cs,Fr OR Group 14 - Metalloids Si,Ge OR Group 15 - Phosphorus P OR Group 16 - Oxygen O OR Group 16 - Sulfur S OR Group 17 - Halogens Br OR Group 8 - Trans.Metals Fe,Ru,Os by Chemical elements

Domain logical expression index: "j"

Similarity boundary:Target: CN(C)c1ccc(C(=C2C=CC(=N{+}(C)(C).Cl{-})C=C2)c2ccc(N(C)C)cc2)cc1
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Alkene AND Ammonium salt AND Aromatic amine AND Overlapping groups by Organic Functional groups (nested) ONLY

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Alkene AND Ammonium salt AND Aromatic amine AND Overlapping groups by Organic Functional groups (nested) ONLY

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Alkene AND Ammonium salt AND Aromatic amine AND Overlapping groups by Organic Functional groups (nested) ONLY

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Aromatic mono- and dialkylamine by in vivo mutagenicity (Micronucleus) alerts by ISS

Domain logical expression index: "o"

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: "p"

Referential boundary: The target chemical should be classified as High (Class III) by Toxic hazard classification by Cramer (with extensions) ONLY

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as High (Class III) by Toxic hazard classification by Cramer (original) ONLY

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as Basic [0,10) AND No pKa value by Ionization at pH = 9

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as Basic [80,90) OR Basic [90,100] OR No pKb value by Ionization at pH = 9

Domain logical expression index: "t"

Parametric boundary:The target chemical should have a value of log Kow which is >= -0.285

Domain logical expression index: "u"

Parametric boundary:The target chemical should have a value of log Kow which is <= 4.99

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
LD50 was estimated to be 711mg/kg bw, when male Fischer 344 rat were exposed with N-(4-{bis[4-(dimethylamino)phenyl]methylene}cyclohexa-2,5-dien-1-ylidene)-N-methylmethanaminium chloride (548-62-9) orally.
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 N-(4-{bis[4-(dimethylamino)phenyl]methylene}cyclohexa-2,5-dien-1-ylidene)-N-methylmethanaminium chloride.LD50 was estimated to be 711 mg/kg bw, when male Fischer 344 rat were exposed with N-(4-{bis[4-(dimethylamino)phenyl]methylene}cyclohexa-2,5-dien-1-ylidene)-N-methylmethanaminium chloride (548-62-9 )orally.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
711 mg/kg bw
Quality of whole database:
Data is Klimicsh 2 and from QSAR Toolbox 3.3. (2017)

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
the study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size
Endpoint conclusion
Endpoint conclusion:
no study available
Quality of whole database:
Waiver

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
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 v3.3 and the QMRF report has been attached.
Qualifier:
equivalent or similar to
Guideline:
other: As mentioned below
Principles of method if other than guideline:
Prediction was done using OECD QSAR toolbox v3.3, 2017
GLP compliance:
not specified
Test type:
other: not specified
Limit test:
yes
Specific details on test material used for the study:
Name of test material (as cited in study report): Crystal violet
- IUPAC name: N-(4-{bis[4-(dimethylamino)phenyl]methylene}cyclohexa-2,5-dien-1-ylidene)-N-methylmethanaminium chloride
- Molecular formula : C25H30N3.Cl
Molecular weight : 407.986 g/mol
- Smiles notation: C(\c1ccc(N(C)C)cc1)(c1ccc(N(C)C)cc1)=C1\C=C\C(=[N+](/C)C)C=C1.[ClH-]
- InChl:1S/C25H30N3.ClH/c1-26(2)22-13-7-19(8-14-22)25(20-9-15-23(16-10-20)27(3)4)21-11-17-24(18-12-21)28(5)6;/h7-18H,1-6H3;1H/q+1;/p-1
- Substance type: Organic
- Physical state: Solid
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
No data available
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
No data available
Duration of exposure:
No data available
Doses:
6869.69 mg/kg bw
No. of animals per sex per dose:
Total:10
male:5
female:5
Control animals:
not specified
Details on study design:
No data available
Statistics:
No data available
Preliminary study:
No data available
Sex:
male/female
Dose descriptor:
LD50
Effect level:
6 869.69 mg/kg bw
Based on:
test mat.
Remarks on result:
other: 50% mortality was observed
Mortality:
No data available
Clinical signs:
No data available
Body weight:
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" or "d" )  and ("e" and ( not "f") )  )  and ("g" and ( not "h") )  )  and ("i" and ( not "j") )  )  and ("k" and ( not "l") )  )  and ("m" and ( not "n") )  )  and "o" )  and "p" )  and "q" )  and "r" )  and "s" )  and ("t" and ( not "u") )  )  and ("v" and "w" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Alkene OR Ammonium salt OR Aromatic amine OR Aryl by Organic Functional groups ONLY

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Alkene OR Ammonium salt OR Aromatic amine OR Overlapping groups by Organic Functional groups (nested) ONLY

Domain logical expression index: "c"

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 Amino, aliphatic attach [-N<] OR Aromatic Carbon [C] OR Olefinic carbon [=CH- or =C<] by Organic functional groups (US EPA) ONLY

Domain logical expression index: "d"

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

Domain logical expression index: "e"

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

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Nucleophilic addition to alpha, beta-unsaturated carbonyl compounds OR AN2 >> Nucleophilic addition to alpha, beta-unsaturated carbonyl compounds >> alpha, beta-Unsaturated Aldehydes OR AN2 >> Schiff base formation OR AN2 >> Schiff base formation >> alpha, beta-Unsaturated Aldehydes OR Michael addition OR Michael addition >> Quinone type compounds OR Michael addition >> Quinone type compounds >> Quinone methides OR Radical OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines OR Radical >> ROS formation after GSH depletion OR Radical >> ROS formation after GSH depletion >> Quinone methides OR SN1 OR SN1 >> Alkylation after metabolically formed carbenium ion species OR SN1 >> Alkylation after metabolically formed carbenium ion species >> Polycyclic Aromatic Hydrocarbon Derivatives OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Single-Ring Substituted Primary Aromatic Amines OR SN2 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 P450-mediated metabolic activation OR SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation >> Polycyclic Aromatic Hydrocarbon Derivatives by DNA binding by OASIS v.1.3

Domain logical expression index: "g"

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

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Non binder, MW>500 OR Non binder, non cyclic structure OR Weak binder, NH2 group by Estrogen Receptor Binding

Domain logical expression index: "i"

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

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Michael Addition OR Michael Addition >> Michael addition on conjugated systems with electron withdrawing group OR Michael Addition >> Michael addition on conjugated systems with electron withdrawing group >> alpha,beta-Carbonyl compounds with polarized double bonds  OR Michael Addition >> Polarised Alkenes OR Michael Addition >> Polarised Alkenes >> Polarised Alkene - alkenyl pyridines, pyrazines, pyrimidines or triazines  OR SN2 OR SN2 >> Interchange reaction with sulphur containing compounds OR SN2 >> Interchange reaction with sulphur containing compounds >> Thiols and disulfide compounds  by Protein binding by OASIS v1.3

Domain logical expression index: "k"

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: "l"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Nucleophilic addition to pyridonimine tautomer of aminopyridoindoles or aminopyridoimidazoles OR AN2 >> Nucleophilic addition to pyridonimine tautomer of aminopyridoindoles or aminopyridoimidazoles >> Heterocyclic Aromatic Amines OR Radical mechanism OR Radical mechanism >> ROS generation and direct attack of hydroxyl radical to the C8 position of nucleoside base OR Radical mechanism >> ROS generation and direct attack of hydroxyl radical to the C8 position of nucleoside base >> Heterocyclic Aromatic Amines OR SE reaction (CYP450-activated heterocyclic amines) OR SE reaction (CYP450-activated heterocyclic amines) >> Direct attack of arylnitrenium cation to the C8 position of nucleoside base OR SE reaction (CYP450-activated heterocyclic amines) >> Direct attack of arylnitrenium cation to the C8 position of nucleoside base >> Heterocyclic Aromatic Amines OR SR reaction (peroxidase-activated heterocyclic amines) OR SR reaction (peroxidase-activated heterocyclic amines) >> Direct attack of arylnitrenium radical to the C8 position of nucleoside base OR SR reaction (peroxidase-activated heterocyclic amines) >> Direct attack of arylnitrenium radical to the C8 position of nucleoside base >> Heterocyclic Aromatic Amines by Protein binding alerts for Chromosomal aberration by OASIS v1.1

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Group 14 - Carbon C AND Group 15 - Nitrogen N AND Group 17 - Halogens Cl AND Group 17 - Halogens F,Cl,Br,I,At by Chemical elements

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Group 1 - Alkali Earth Li,Na,K,Rb,Cs,Fr OR Group 14 - Metalloids Si,Ge OR Group 15 - Phosphorus P OR Group 16 - Oxygen O by Chemical elements

Domain logical expression index: "o"

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

Domain logical expression index: "p"

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 Olefinic carbon [=CH- or =C<] by Organic functional groups (US EPA) ONLY

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as High (Class III) by Toxic hazard classification by Cramer (with extensions) ONLY

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as High (Class III) by Toxic hazard classification by Cramer (original) ONLY

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as No superfragment by Superfragments ONLY

Domain logical expression index: "t"

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

Domain logical expression index: "u"

Referential boundary: The target chemical should be classified as Multi Cyclic Hydrocarbons by rtER Expert System ver.1 - USEPA

Domain logical expression index: "v"

Parametric boundary:The target chemical should have a value of log Kow which is >= -0.382

Domain logical expression index: "w"

Parametric boundary:The target chemical should have a value of log Kow which is <= 1.99

Interpretation of results:
other: Not classified
Conclusions:
LD50 was estimated to be 6869.69mg/kg bw, when male and female New Zealand White rabbits were exposed with N-(4-{bis[4-(dimethylamino)phenyl]methylene}cyclohexa-2,5-dien-1-ylidene)-N-methylmethanaminium chloride (548-62-9) by dermal application.
Executive summary:

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute dermal toxicity was estimatedN-(4-{bis[4-(dimethylamino)phenyl]methylene}cyclohexa-2,5-dien-1-ylidene)-N-methylmethanaminium chloride (548-62-9) .The LD50 was estimated to be 6869.69 mg/kg bw when male and female New Zealand White rabbits were exposed with N-(4-{bis[4-(dimethylamino)phenyl]methylene}cyclohexa-2,5-dien-1-ylidene)-N-methylmethanaminium chloride (548-62-9) by dermal application.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
6 869.69 mg/kg bw
Quality of whole database:
Data is Klimicsh 2 and from QSAR Toolbox 3.3. (2017)

Additional information

Acute oral toxicity

In different studies,N-(4-{bis[4-(dimethylamino)phenyl]methylene}cyclohexa-2,5-dien-1-ylidene)-N-methylmethanaminium chloride (548-62-9 )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 forN-(4-{bis[4-(dimethylamino)phenyl]methylene}cyclohexa-2,5-dien-1-ylidene)-N-methylmethanaminium chloride (548-62-9 ).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 N-(4-{bis[4-(dimethylamino)phenyl]methylene}cyclohexa-2,5-dien-1-ylidene)-N-methylmethanaminium chloride.LD50 was estimated to be 711 mg/kg bw, when male Fischer 344 rat were exposed with N-(4-{bis[4-(dimethylamino)phenyl]methylene}cyclohexa-2,5-dien-1-ylidene)-N-methylmethanaminium chloride (548-62-9 )orally.

Based on the QSAR prediction done using the Danish (Q)SAR Database, the LD50 was estimated to be 440mg/kg bw on rat for substance N-(4-{bis[4-(dimethylamino)phenyl]methylene}cyclohexa-2,5-dien-1-ylidene)-N-methylmethanaminium chloride (548-62-9).

Also it is further supported by experimental study given byU.S .National library of medicine (ChemID plusA TOXNET DATABASE.2017).Acute oral toxicity study was done in rats using basic violet 3 (548-62-9) 50% mortality was observed at dose 420mg/kg bw. Hence LD50 was considered to be 420mg/kg body weight.When rats was treated with basic violet 3 (548-62-9) orally.

Also it is further supported by experimental study given by Catherine Diamante et.al.(International Journal of Toxicology 28(Suppl 3) 193S-204S, 2010),Acute oral toxicity study was done in 24 adult rats using basic violet 3 (548-62-9).The 1% or 2% solution of test material was prepared in water and given by oral gavage route.50% mortality was observed at dose 650 mg/kg bw.HenceLD50 was considered to be 650 mg/kg body weight. When rats was treated with basic violet 3 (548-62-9)orally.

Also it is further supported by experimental study given inU.S .National library of medicine (ChemID plusA TOXNET DATABASE.2017).on structurally similar read across substanceAuramine hydrochloride (2465-27-2),Acute oral toxicity study was done in mouse using Auramine hydrochloride (2465-27-2). 50% mortality was observed at dose 420mg/kg bw. Hence LD50 was considered to be 480mg/kg body weight.When rats were treated with Auramine hydrochloride (2465-27-2) orally.

 

Thus, based on the above studies and predictions onN-(4-{bis[4-(dimethylamino)phenyl]methylene}cyclohexa-2,5-dien-1-ylidene)-N-methylmethanaminium chloride (548-62-9 )and its read across substances, it can be concluded that LD50 value is 711 mg/kg bw. Thus, comparing this value with the criteria of CLPN-(4-{bis[4-(dimethylamino)phenyl]methylene}cyclohexa-2,5-dien-1-ylidene)-N-methylmethanaminium chloride (548-62-9 )can be classified as “Category IV”for acute oral toxicity.

Acute inhalation toxicity

Gentian violet has a very low vapor pressure (2.57 X 10-12 Pa), so the potential for the generation of inhalable vapours is very low, also the normal conditions of use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be highly unlikely and therefore this end point was considered for waiver

 

Acute dermal toxicity

In different studies,N-(4-{bis[4-(dimethylamino)phenyl]methylene}cyclohexa-2,5-dien-1-ylidene)-N-methylmethanaminium chloride (548-62-9 )has been investigated for acute dermal 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 rabbits forN-(4-{bis[4-(dimethylamino)phenyl]methylene}cyclohexa-2,5-dien-1-ylidene)-N-methylmethanaminium chloride (548-62-9 ).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 dermal toxicity was estimatedN-(4-{bis[4-(dimethylamino)phenyl]methylene}cyclohexa-2,5-dien-1-ylidene)-N-methylmethanaminium chloride (548-62-9) .The LD50 was estimated to be 6869.69 mg/kg bw when male and female New Zealand White rabbits were exposed with N-(4-{bis[4-(dimethylamino)phenyl]methylene}cyclohexa-2,5-dien-1-ylidene)-N-methylmethanaminium chloride (548-62-9) by dermal application.

Also it is further supported by experimental study givenby U.S .National library of medicine (ChemID plusA TOXNET DATABASE.2017)on structurally similar read across substanceNaphtha (petroleum), catalytic reformed (68955-35-1) , Acute dermal toxicity study was done in 4 male and 4 female New Zealand White rabbits using test material Naphtha (petroleum), catalytic reformed (68955-35-1).The skins of two male and two female animals were abraded before application. No mortality observed at dose 2000mg/kg. Clinical signs like moderate to severe skin irritation were observed in treated rabbits. Necroscopy revealed thickened and crusted skin on test areas and red focii on the cortex of one rabbit kidney.HenceLD50 was considered to be>2000mg/kg body weight.When rabbits were treated with Naphtha (petroleum), catalytic reformed (68955-35-1) by dermal application.

Also it is further supported by experimental study givenby U.S .National library of medicine (ChemID plusA TOXNET DATABASE.2017)on structurally similar read across substanceNaphtha (petroleum), light catalytic reformed (64741 -63 -5) , Acute dermal toxicity study was done in 4 male and 4 female New Zealand White rabbits using test material Naphtha (petroleum), light catalytic reformed (64741 -63 -5).The skins of two male and two female animals were abraded before application. No mortality observed at dose 2000mg/kg. Clinical signs like moderate to severe skin irritation were observed in treated rabbits. Necroscopy revealed thickened and crusted skin on test areas and red focii on the cortex of one rabbit kidney.HenceLD50 was considered to be >2000mg/kg body weight.When rabbits were treated with Naphtha (petroleum), light catalytic reformed (64741 -63 -5) by dermal application.

 Thus, based on the above studies and predictions onN-(4-{bis[4-(dimethylamino)phenyl]methylene}cyclohexa-2,5-dien-1-ylidene)-N-methylmethanaminium chloride (548-62-9 )and its read across substances, it can be concluded that LD50 value is 6869.69mg/kg bw. Thus, comparing this value with the criteria of CLPN-(4-{bis[4-(dimethylamino)phenyl]methylene}cyclohexa-2,5-dien-1-ylidene)-N-methylmethanaminium chloride (548-62-9 )can be “Not classified” for acute dermal toxicity.

Justification for classification or non-classification

Thus, comparing this value with the criteria of CLPN-(4-{bis[4-(dimethylamino)phenyl]methylene}cyclohexa-2,5-dien-1-ylidene)-N-methylmethanaminium chloride (548-62-9 )can be classified as “Category IV” for acute oral toxicity and “Not classified” for acute dermal toxicity.

Acute inhalation toxicity

Gentian violet has a very low vapor pressure (2.57 X 10-12 Pa), so the potential for the generation of inhalable vapours is very low, also the normal conditions of use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be highly unlikely and therefore this end point was considered for waiver