3,7-bis(diethylamino)phenoxazin-5-ium tetrachlorozincate (2:1)

Endpoint summary

Description of key information

Prediction model based estimation and data available for the target chemical was reviewed to determine the toxic nature of 3,7-bis(diethylamino)phenoxazin-5-ium tetrachlorozincate (2:1) (63589-47-9)upon repeated exposure by oral, dermal and inhalation route of exposure. The studies are as mentioned below:

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 3,7-bis(diethylamino)phenoxazin-5-ium tetrachlorozincate (2:1) (63589-47-9). The study assumed the use of male and female Wistar rats in subchronic study of 28days. No significant alterations were noted at the dose level of 667.080mg/Kg bw/day. The predicted No Observed Adverse Effect Level (NOAEL) for compound3,7-bis(diethylamino) phenoxazin-5-ium tetrachlorozincate (2:1) is considered to be 667.080mg/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:

repeated dose toxicity: oral, other

Type of information:

(Q)SAR

Adequacy of study:

key study

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 - 3,7-bis(diethylamino)phenoxazin-5-ium tetrachlorozincate (2:1)
Molecular Weight - 324.445 g/mole
InChI - 1S/C20H26N3O/c1-5-22(6-2)15-9-11-17-19(13-15)24-20-14-16(23(7-3)8-4)10-12-18(20)21-17/h9-14H,5-8H2,1-4H3/q+1
Smiles - c1cc(cc2[o+]c3cc(ccc3nc12)N(CC)CC)N(CC)CC

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

Not specified.

Route of administration:

oral: gavage

Vehicle:

not specified

Details on oral exposure:

Not specified.

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

Not specified.

Duration of treatment / exposure:

28 days

Frequency of treatment:

Not specified.

Remarks:

Not specified.

No. of animals per sex per dose:

Not specified.

Control animals:

yes, concurrent vehicle

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

Details on results:

Not specified.

Key result

Dose descriptor:

NOAEL

Effect level:

667.08 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 observed

Critical effects observed:

not specified

Treatment related:

not specified

Dose response relationship:

not specified

Relevant for humans:

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" or "b" or "c" )  and ("d" and ( not "e") )  )  and ("f" and ( not "g") )  )  and ("h" and ( not "i") )  )  and "j" )  and ("k" and "l" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Zinc metal and salts by OECD HPV Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Soluble complexes of Zinc by US-EPA New Chemical Categories

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as SN1 AND SN1 >> Nitrenium Ion formation AND SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine by DNA binding by OECD

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 >> Tertiary aromatic amine by DNA binding by OECD

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as No alert found OR SN1 >> Iminium Ion Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines OR SN1 >> Nitrenium Ion formation >> Aromatic azo OR SN1 >> Nitrenium Ion formation >> Primary aromatic amine OR SN2 OR SN2 >> Direct Acting Epoxides and related OR SN2 >> Direct Acting Epoxides and related >> Epoxides by DNA binding by OECD

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Non binder, MW>500 by Estrogen Receptor Binding

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 Not categorized by Repeated dose (HESS)

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as 4,4'-Diethylaminoethoxyhexestrol (Hepatotoxicity) Alert by Repeated dose (HESS)

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Aromatic amine AND Fused carbocyclic aromatic AND Fused heterocyclic aromatic AND Overlapping groups by Organic Functional groups (nested) ONLY

Domain logical expression index: "k"

Parametric boundary:The target chemical should have a value of log BCF max which is >= 1.98 log(L/kg wet)

Domain logical expression index: "l"

Parametric boundary:The target chemical should have a value of log BCF max which is <= 3.42 log(L/kg wet)

Conclusions:

The predicted No Observed Adverse Effect Level (NOAEL) for 3,7-bis(diethylamino)phenoxazin-5-ium tetrachlorozincate (2:1) (63589-47-9) is considered to be 667.080mg/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 compound3,7-bis(diethylamino)phenoxazin-5-ium tetrachlorozincate (2:1) (63589-47-9). The study assumed the use of male and female Wistar rats in subchronic study of 28days. No significant alterations were noted at the dose level of 667.080mg/Kg bw/day. The predicted No Observed Adverse Effect Level (NOAEL) for compound3,7-bis(diethylamino) phenoxazin-5-ium tetrachlorozincate (2:1) is considered to be 667.080mg/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

667.08 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

K2 data from OECD QSAR prediction

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:

Prediction model based estimation and data available for the target chemical was reviewed to determine the toxic nature of 3,7-bis(diethylamino)phenoxazin-5-ium tetrachlorozincate (2:1) (63589-47-9)upon repeated exposure by oral, dermal and inhalation route of exposure. The studies are as mentioned below:

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 3,7-bis(diethylamino)phenoxazin-5-ium tetrachlorozincate (2:1) (63589-47-9). The study assumed the use of male and female Wistar rats in subchronic study of 28days. No significant alterations were noted at the dose level of 667.080mg/Kg bw/day. The predicted No Observed Adverse Effect Level (NOAEL) for compound3,7-bis(diethylamino) phenoxazin-5-ium tetrachlorozincate (2:1) is considered to be 667.080mg/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.

 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 3,7-bis(diethylamino)phenoxazin-5-ium tetrachlorozincate (2:1) (63589-47-9), which is reported as 2.27E-06Pa 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 micron to 53 micron which is much larger size range compared to the inhalable particulate matter. Thus, exposure to inhalable dust, mist and vapour of the chemical 3,7-bis(diethylamino)phenoxazin-5-ium tetrachlorozincate (2:1) is highly unlikely. Therefore this study is considered for waiver.

Repeated dermal study

The acute toxicity value for 3,7-bis(diethylamino)phenoxazin-5-ium tetrachlorozincate (2:1) (as provided in section 7.2.3) is 8222.0 mg/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 3,7-bis(diethylamino)phenoxazin-5-ium tetrachlorozincate (2:1) (63589-47-9) shall not exhibit 28 day repeated dose toxicity by the dermal route. In addition, there is no data available that suggests that 3,7-bis(diethylamino)phenoxazin-5-ium tetrachlorozincate (2:1) (63589-47-9)shall exhibit repeated dose toxicity by the dermal route. Hence this end point was considered for waiver.

Justification 

 

Based on the data available for the target chemical and its prediction, 3,7-bis(diethylamino) phenoxazin-5-ium tetrachlorozincate (2:1) (63589-47-9)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 prediction, 3,7-bis(diethylamino) phenoxazin-5-ium tetrachlorozincate (2:1) (63589-47-9)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.