Bis[[4-[[4-(diethylamino)phenyl][4-(ethylamino)-1-naphthyl]methylene]cyclohexa-2,5-dien-1-ylidene]diethylammonium] dicopper(1+) hexa(cyano-C)ferrate(4-)

Endpoint summary

Description of key information

Prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the five closest read across substances, repeated dose oral toxicity was predicted for the test compound Bis[[4-[[4-(diethylamino)phenyl][4-(ethylamino)-1-naphthyl]methylene] cyclohexa-2,5-dien-1-ylidene] diethylammonium] dicopper(1+) hexa(cyano-C)ferrate(4-)(82338-76-9). The study assumed the use of male and female Crj: CD(SD)rats in chronic study of 90 days . No significant alterations were noted at the dose level of 267.56mg/Kg bw/day. The predicted No Observed Adverse Effect Level (NOAEL) forBis[[4-[[4-(diethylamino)phenyl][4-(ethylamino)-1-naphthyl]methylene]cyclohexa-2,5-dien-1-ylidene]diethylammonium] dicopper(1+) hexa(cyano-C)ferrate(4-is considered to be 267.56mg/Kg bw/day. Based on this value it can be concluded that the substance is considered to not toxic as per the criteria mentioned in CLP regulation

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Endpoint:

chronic 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:

according to guideline

Guideline:

other: AS mention below

Principles of method if other than guideline:

Prediction is done using OECD QSAR Toolbox version 3.3, 2017

GLP compliance:

not specified

Limit test:

no

Specific details on test material used for the study:

Name: Bis[[4-[[4-(diethylamino)phenyl][4-(ethylamino)-1-naphthyl]methylene]cyclohexa-2,5-dien-1-ylidene]diethylammonium] dicopper(1+) hexa(cyano-C)ferrate(4-)
Common Name: Pigment Blue 62
SMILES:CCNc1ccc(C(=C2C=CC(=N{+}(CC)CC)C=C2)c2ccc(N(CC)CC)cc2)c2ccccc12
InChI:1S/2C33H39N3.6CN.2Cu.Fe/c2*1-6-34-32-24-23-31(29-13-11-12-14-30(29)32)33(25-15-19-27(20-16-25)35(7-2)8-3)26-17-21-28(22-18-26)36(9-4)10-5;6*1-2;;;/h2*11-24H,6-10H2,1-5H3;;;;;;;;;/q;;;;;;;;2*+1;-4/p+2
Molecular Weight: 1296.445 g/mole
Molecular Formula: C33H40N3.1/2C6FeN6.Cu

Species:

rat

Strain:

Crj: CD(SD)

Details on species / strain selection:

Not specified.

Sex:

male/female

Details on test animals or test system and environmental conditions:

Not specified.

Route of administration:

oral: gavage

Details on route of administration:

Not specified.

Vehicle:

not specified

Details on oral exposure:

Not specified.

Details on analytical verification of doses or concentrations:

Not specified.

Duration of treatment / exposure:

90 days

Frequency of treatment:

Not specified.

Remarks:

Not specified.

No. of animals per sex per dose:

Not specified.

Control animals:

not specified

Details on study design:

Not specified.

Positive control:

Not specified.

Observations and examinations performed and frequency:

Not specified.

Sacrifice and pathology:

Not specified.

Other examinations:

Not specified.

Statistics:

Not specified.

Clinical signs:

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

Gross pathological findings:

not specified

Neuropathological findings:

not specified

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

not specified

Other effects:

not specified

Description (incidence and severity):

Not specified.

Dose descriptor:

NOAEL

Effect level:

267.567 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: No significant effect were observed at this dose

Remarks on result:

other: No toxic effect were observed

Critical effects observed:

not specified

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" and ("b" and ( not "c") )  )  and ("d" and ( not "e") )  )  and "f" )  and ("g" and "h" )  )

Domain logical expression index: "a"

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

Domain logical expression index: "b"

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

Domain logical expression index: "c"

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

Domain logical expression index: "d"

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

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Michael addition OR Michael addition >> Quinone type compounds OR Michael addition >> Quinone type compounds >> Quinone methides OR Radical OR Radical >> ROS formation after GSH depletion OR Radical >> ROS formation after GSH depletion >> Quinone methides OR SN2 OR SN2 >> Alkylation, direct acting epoxides and related OR SN2 >> Alkylation, direct acting epoxides and related >> Epoxides and Aziridines by DNA binding by OASIS v.1.3

Domain logical expression index: "f"

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: "g"

Parametric boundary:The target chemical should have a value of log Kow which is >= 1.86

Domain logical expression index: "h"

Parametric boundary:The target chemical should have a value of log Kow which is <= 8.83

Conclusions:

The predicted No Observed Adverse Effect Level (NOAEL) for Bis[[4-[[4-(diethylamino)phenyl][4-(ethylamino)-1-naphthyl]methylene]cyclohexa-2,5-dien-1-ylidene]diethylammonium] dicopper(1+) hexa(cyano-C)ferrate(4-)(82338-76-9) is considered to be 267.56mg/Kg bw/day.

Executive summary:

Based on the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the five closest read across substances, repeated dose oral toxicity was predicted for the test compound Bis[[4-[[4-(diethylamino)phenyl][4-(ethylamino)-1-naphthyl]methylene] cyclohexa-2,5-dien-1-ylidene] diethylammonium] dicopper(1+) hexa(cyano-C)ferrate(4-)(82338-76-9). The study assumed the use of male and female Crj: CD(SD)rats in chronic study of90 days . No significant alterations were noted at the dose level of 267.56mg/Kg bw/day. The predicted No Observed Adverse Effect Level (NOAEL) for Bis[[4-[[4-(diethylamino)phenyl][4-(ethylamino)-1-naphthyl]methylene]cyclohexa-2,5-dien-1-ylidene]diethylammonium] dicopper(1+) hexa(cyano-C)ferrate(4- is considered to be 267.56mg/Kg bw/day. Based on this value it can be concluded that the substance is considered to not toxic as per the criteria mentioned in CLP regulation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

267.56 mg/kg bw/day

Study duration:

chronic

Species:

rat

Quality of whole database:

K2 data from OECD QSAR toolbox version 3.3

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Repeated dose oral toxicity:

Based on the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the five closest read across substances, repeated dose oral toxicity was predicted for the test compound Bis[[4-[[4-(diethylamino)phenyl][4-(ethylamino)-1-naphthyl]methylene] cyclohexa-2,5-dien-1-ylidene] diethylammonium] dicopper(1+) hexa(cyano-C)ferrate(4-)(82338-76-9). The study assumed the use of male and female Crj: CD(SD)rats in chronic study of90 days . No significant alterations were noted at the dose level of267.56mg/Kg bw/day. The predicted No Observed Adverse Effect Level (NOAEL) forBis[[4-[[4-(diethylamino)phenyl][4-(ethylamino)-1-naphthyl]methylene]cyclohexa-2,5-dien-1-ylidene]diethylammonium] dicopper(1+) hexa(cyano-C)ferrate(4-is considered to be 267.56mg/Kg bw/day. Based on this value it can be concluded that the substance is considered to not toxic as per the criteria mentioned in CLP regulation

Based on the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the five closest read across substances, repeated dose oral toxicity was predicted for the test compound Bis[[4-[[4-(diethylamino)phenyl][4-(ethylamino)-1-naphthyl]methylene]cyclohexa-2,5-dien-1-ylidene]

diethylammonium] dicopper(1+) hexa(cyano-C)ferrate(4-)(82338-76-9). The study assumed the use of male and female Crj: CD(SD)rats in chronic study of90 days . No significant alterations were noted at the dose level of 462.0mg/Kg bw/day. The predicted No Observed Adverse Effect Level (NOAEL) for Dialkyl(C1-C14)dithiophosphoric acid, zinc salt is considered to be 267.56mg/Kg bw/day. Based on this value it can be concluded that the substance is considered to not toxic as per the criteria mentioned in CLP regulation.

Another Repeated dose toxicity study was performed by U. S. National Library of Medicine (HSDB (Hazardous Substances Data Bank, 2017) to determine the oral toxic nature Ametryne (834-12-8). The data is taken from Read across substance. The read across substance share a high similarity in structure. So it is acceptable to tale data from analogous structure. Repeated dose toxicity study for Ametryne was assessed to evaluate its toxic potential. The test material was exposed at the concentration of0,100, 250, or 500 mg/kg/day in male and female rats by oral gavage for 28 days. The rats were observed for clinical sign, mortality, body weight, gross and histipathology.Mortality was observed at the dose level of 250 and 500mg/kg/day. At the dose level of 500 mg/kg/day in treated animals severe vascular congestion, centrilobular liver necrosis and fatty degeneration of individual liver cells were observed compare to control. No significant effect and mortality was observed at 100 mg/kg/day in any treated animals. Therefore NOAEL was considered to be 100 mg/kg/day in male and female rats by subchronic study by oral gavage.

Repeated inhalation study:

According to Annex IX of the REACH regulation, testing by the inhalation route is appropriate only if exposure of humans via inhalation is likely. Taking into account the low vapour pressure of the substance Bis[[4-[[4-(diethylamino)phenyl][4-(ethylamino)-1-naphthyl]methylene]cyclohexa-2,5-dien-1-ylidene]diethylammonium] dicopper(1+) hexa(cyano-C)ferrate(4-) , which is reported as 2.9E-26 Pa at 25 C. Also considering the particle size distribution of the substance the majority of the particles were found to be in the size of 150 micrometer which is much larger size range compared to the inhalable particulate matter. Thus, exposure to inhalable dust, mist and vapour of the chemical 1-hydroxybenzotriazole is highly unlikely. Therefore this study is considered for waiver.

Repeated dermal study

The acute toxicity value for Bis[[4-[[4-(diethylamino)phenyl][4-(ethylamino)-1-naphthyl]methylene]cyclohexa-2,5-dien-1-ylidene]diethylammonium] dicopper(1+) hexa(cyano-C)ferrate(4-)(as provided in section 7.2.3) is 6943.0mg/kg body weight. Also, given the use of the chemical; repeated exposure by the dermal route is unlikely since the use of gloves is common practice in industries. Thus, it is expected that Bis[[4-[[4-(diethylamino)phenyl][4-(ethylamino)-1-naphthyl]methylene]cyclohexa-2,5-dien-1-ylidene]diethylammonium] dicopper(1+) hexa(cyano-C)ferrate(4-)(82338-76-9) shall not exhibit 28 day repeated dose toxicity by the dermal route. In addition, there is no data available that suggests that Bis[[4-[[4-(diethylamino)phenyl][4-(ethylamino)-1-naphthyl]methylene]cyclohexa-2,5-dien-1-ylidene]diethylammonium] dicopper(1+) hexa(cyano-C)ferrate(4-)shall exhibit repeated dose toxicity by the dermal route. Hence this end point was considered for waiver.

Based on the data available for the target chemical and its prediction, Bis[[4-[[4-(diethylamino)phenyl][4-(ethylamino)-1-naphthyl]methylene]cyclohexa-2,5-dien-1-ylidene]diethylammonium] dicopper(1+) hexa(cyano-C)ferrate(4-)(82338-76-9) does not exhibit toxic nature upon repeated exposure by oral, inhalation and dermal route of exposure and hence is not likely to classify as per the criteria mentioned in CLP regulation.

Justification for classification or non-classification

Based on the data available for the target chemical and its read across,Bis[[4-[[4-(diethylamino)phenyl][4-(ethylamino)-1-naphthyl]methylene] cyclohexa-2,5-dien-1-ylidene ] diethylammonium] dicopper(1+) hexa(cyano-C)ferrate(4-)(82338-76-9) does not exhibit toxic nature upon repeated exposure by oral, inhalation and dermal route of exposure and hence is not likely to classify as per the criteria mentioned in CLP regulation.