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

Endpoint summary

Description of key information

The skin sensitization potential of 3,7-bis(diethylamino)phenoxazin-5-ium tetrachlorozincate (2:1) (CAS No: 63589-47-9) was estimated using prediction model OECD QSAR toolbox version 3.3 and the data available forits closest read across substances with log kow as the primary descriptor. Thus based on the predictions as well as its read across substances and applying weight of evidence, it can be concluded that the chemical 3,7-bis(diethylamino)phenoxazin-5-ium tetrachlorozincate (2:1) (CAS No: 63589-47-9) failed to induce contact sensitization and hence is considered to be not sensitizing to and can be classified under the category ˋ Not Classified’ as per CLP regulation.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

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 version 3.3 and QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: estimated data

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.3

GLP compliance:

not specified

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

not specified

Specific details on test material used for the study:

- Name of test material (IUPAC name): 3,7-bis(diethylamino)phenoxazin-5-ium tetrachlorozincate (2:1)
- Molecular formula: C40H52Cl4N6O2Zn
- Molecular weight: 856.093 g/mol
- Smiles notation: [o+]1c2cc(ccc2nc2ccc(N(CC)CC)cc12)N(CC)CC.[Zn+2].[ClH-].[ClH-].[ClH-].[ClH-].[o+]1c2cc(ccc2nc2c1cc(cc2)N(CC)CC)N(CC)CC
- InChl: 1S/2C20H26N3O.4ClH.Zn/c2*1-5-22(6-2)15-9-11-17-19(13-15)24-20-14-16(23(7-3)8-4)10-12-18(20)21-17;;;;;/h2*9-14H,5-8H2,1-4H3;4*1H;/q2*+1;;;;;+2/p-4
- Substance type: Organic
- Physical state: Solid

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

male/female

Details on test animals and environmental conditions:

No data available

Route:

intradermal and epicutaneous

Vehicle:

not specified

Concentration / amount:

No data available

Day(s)/duration:

No data available

Adequacy of induction:

not specified

No.:

#1

Route:

epicutaneous, occlusive

Concentration / amount:

No data available

Day(s)/duration:

72 hours

Adequacy of challenge:

not specified

No. of animals per dose:

20

Details on study design:

No data available

Reading:

1st reading

Hours after challenge:

72

Group:

test chemical

Dose level:

No data available

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

No skin sensitization was observed.

Remarks on result:

no indication of skin sensitisation

Cellular proliferation data / Observations:

No skin sensitization was observed.

The prediction was based on dataset comprised from the following descriptors: "Skin Sensitisation"
Estimation method: Takes highest mode value from the 7 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 ( not "l") )  )  and "m" )  and "n" )  and ("o" and "p" )  )

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 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 Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> Fused-Ring Primary Aromatic Amines OR Non-specific OR Non-specific >> Incorporation into DNA/RNA, due to structural analogy with  nucleoside bases    OR Non-specific >> Incorporation into DNA/RNA, due to structural analogy with  nucleoside bases    >> Specific Imine and Thione Derivatives OR Radical OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Fused-Ring Primary Aromatic Amines OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitro Azoarenes OR Radical >> Radical mechanism via ROS formation (indirect) >> Specific Imine and Thione Derivatives OR SN1 OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Fused-Ring Primary Aromatic Amines OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitro Azoarenes OR SN1 >> Nucleophilic substitution on diazonium ions OR SN1 >> Nucleophilic substitution on diazonium ions >> Specific Imine and Thione Derivatives 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 cyclization OR SN2 >> Alkylation, direct acting epoxides and related after cyclization >> Nitrogen Mustards by DNA binding by OASIS v.1.3

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, non cyclic structure OR Non binder, without OH or NH2 group OR Strong binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "h"

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

Domain logical expression index: "i"

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 >> Cyanoalkenes OR SN1 OR SN1 >> Carbenium ion formation (enzymatic) OR SN1 >> Carbenium ion formation (enzymatic) >> Carbenium ion by Protein binding by OASIS v1.3

Domain logical expression index: "j"

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

Domain logical expression index: "k"

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

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Alkali Earth by Groups of elements

Domain logical expression index: "m"

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

Domain logical expression index: "n"

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

Domain logical expression index: "o"

Parametric boundary:The target chemical should have a value of log Kow which is >= 8.71

Domain logical expression index: "p"

Parametric boundary:The target chemical should have a value of log Kow which is <= 16.6

Interpretation of results:

other: Not sensitizing

Conclusions:

The chemical 3,7-bis(diethylamino)phenoxazin-5-ium tetrachlorozincate (2:1) (CAS No: 63589-47-9)was estimated to be not sensitising to the skin of Dunkin-Hartley guinea pigs. Based on the estimated result 3,7-bis(diethylamino)phenoxazin-5-ium tetrachlorozincate (2:1) (CAS No: 63589-47-9)failed to induce skin sanitization effects and hence is considered to be not sensitizing to Dunkin-Hartley guinea pigs.

Executive summary:

The skin sensitization potential of 3,7-bis(diethylamino)phenoxazin-5-ium tetrachlorozincate (2:1) (CAS No: 63589-47-9)was estimated using OECD QSAR toolbox version 3.3 with log Pow as the primary descriptor. The chemical 3,7-bis(diethylamino)phenoxazin-5-ium tetrachlorozincate (2:1) (CAS No: 63589-47-9)was estimated to be not sensitising to the skin of Dunkin-Hartley guinea pigs. Based on the estimated result 3,7-bis(diethylamino)phenoxazin-5-ium tetrachlorozincate (2:1) (CAS No: 63589-47-9)failed to induce skin sanitization effects and hence is considered to be not sensitizing to Dunkin-Hartley guinea pigs and can be classified under the category ˋ Not Classified’ as per CLP regulation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Skin sensitization:

Various studieshas been investigated for the test chemical3,7-bis(diethylamino)phenoxazin-5-ium tetrachlorozincate (2:1) (CAS No: 63589-47-9)to observe the potential for skin sensitization to a greater or lesser extent. The studies are based on in vivo experiments in guinea pigs for target chemical3,7-bis(diethylamino)phenoxazin-5-ium tetrachlorozincate (2:1) (CAS No: 63589-47-9) and its closest read across substance with log kow as the primary descriptorbis (2-ethylhexyl) zinc dithiophosphate (CAS No: 4259-15-8) and Zinc bis (O, O-bis (1, 3-dimethylbutyl) dithiophosphate(CAS No: 2215–35–2).The predicted data using the OECD QSAR toolbox has also been compared with the experimental data and summarized as below;

 

The skin sensitization potential of 3,7-bis(diethylamino)phenoxazin-5-ium tetrachlorozincate (2:1) (CAS No: 63589-47-9)was estimated using OECD QSAR toolbox version 3.3 with log Pow as the primary descriptor. The chemical 3,7-bis(diethylamino)phenoxazin-5-ium tetrachlorozincate (2:1) (CAS No: 63589-47-9)was estimated to be not sensitising to the skin of Dunkin-Hartley guinea pigs. Based on the estimated result 3,7-bis(diethylamino)phenoxazin-5-ium tetrachlorozincate (2:1) (CAS No: 63589-47-9)failed to induce skin sanitization effects and hence is considered to be not sensitizing to Dunkin-Hartley guinea pigs.

 

The MAK Collection for Occupational Health and Safety {Bis(2-ethylhexyl)zinkdithiophosphat [MAK Value Documentation in German language, 2004]. The MAK Collection for Occupational Health and Safety. 1–14. 2012} conducted a Buehler testof read across chemicalbis (2-ethylhexyl) zinc dithiophosphate (CAS No: 4259-15-8) in guinea pigs according to OECD Test Guideline 406.Induction was carried out once a week for three consecutive weeks with 5% of the test substance in mineral oil, the lowest irritating concentration, provocation 2 weeks after the last application with 1 % in mineral oil, the highest non-irritating concentration. The control group was tested only with mineral oil. For comparison, historical positive controls were used with 1-chloro-2,4- dinitrobenzene and α-hexyl cinnamic aldehyde.The treated guinea pigs showed a negative result (3/20 degree 1 reactions in comparison to 1/20 degree 1 reactions in the solvent control).Hence the chemical bis (2-ethylhexyl) zinc dithiophosphate (CAS No: 4259-15-8) was considered to be not sensitizing to the skin of guinea pigs in a Buehler test.

 

The above results were supported by the experimental report reported by EUROPEAN COMMISSION – European Chemicals Bureau {IUCLID DATABSE- EUROPEAN COMMISSION – European Chemicals Bureau- EUROPEAN COMMISSION – 18–FEB–2000} for read across substance Zinc bis (O, O-bis (1, 3-dimethylbutyl) dithiophosphate(CAS No: 2215–35–2)according toBuehler Test. The material was tested on guinea pigs skin at a concentration 5% w/w dilution of the test article in white mineral oil which did not produce any sensitization reactions in any of 10 test animals. Therefore based upon study, it can be concluded that the Zinc bis (O, O-bis (1, 3-dimethylbutyl) dithiophosphate(CAS No: 2215–35–2) was not sensitizing to guinea pigs.

 

Thus on the basis of available data for thetarget chemical3,7-bis(diethylamino)phenoxazin-5-ium tetrachlorozincate (2:1) (CAS No: 63589-47-9) and its closest read across substance with log kow as the primary descriptorbis (2-ethylhexyl) zinc dithiophosphate (CAS No: 4259-15-8) and Zinc bis (O, O-bis (1, 3-dimethylbutyl) dithiophosphate(CAS No: 2215–35–2),it can be concluded thatchemical 3,7-bis(diethylamino)phenoxazin-5-ium tetrachlorozincate (2:1) (CAS No: 63589-47-9) is unable to cause skin sensitization and considered as non-skin sensitizer. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

The skin sensitization potential of test substance 3,7-bis(diethylamino)phenoxazin-5-ium tetrachlorozincate (2:1) (CAS No: 63589-47-9) and its closest read across substance with log kow as the primary descriptorbis (2-ethylhexyl) zinc dithiophosphate (CAS No: 4259-15-8) and Zinc bis (O, O-bis (1, 3-dimethylbutyl) dithiophosphate(CAS No: 2215–35–2) were observed in various studies. From the results obtained from these studies it is concluded that the chemical 3,7-bis(diethylamino)phenoxazin-5-ium tetrachlorozincate (2:1) (CAS No: 63589-47-9) is not likely to cause skin sensitization and hence can be classified as non-skin sensitizer.