Lithium bis[2-[(4,5-dihydro-3-methyl-5-oxo-1-phenyl-1H-pyrazol-4-yl)azo]benzoato(2-)]chromate(1-)

Endpoint summary

Description of key information

Skin Sensitization:

The skin sensitization potential of lithium bis[2-[(4,5-dihydro-3-methyl-5-oxo-1-phenyl-1H-pyrazol-4-yl)azo]benzoato(2-)]chromate(1-) was estimated by SSS (2018) using OECD QSAR toolbox v3.4 with log kow as the primary descriptor. Lithium bis[2-[(4,5-dihydro-3-methyl-5-oxo-1-phenyl-1H-pyrazol-4-yl)azo]benzoato(2-)]chromate(1-) was predicted to be non sensitizing to the skin of female Hartley guinea pigs.

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 v3.4 and the QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: Estimated data

Principles of method if other than guideline:

Prediction was done using OECD QSAR toolbox v3.4

GLP compliance:

not specified

Type of study:

guinea pig maximisation test

Specific details on test material used for the study:

- Name of test material: Lithium bis[2-[(4,5-dihydro-3-methyl-5-oxo-1-phenyl-1H-pyrazol-4-yl)azo]benzoato(2-)]chromate(1-)
- IUPAC name: Lithium bis[2-[(4,5-dihydro-3-methyl-5-oxo-1-phenyl-1H-pyrazol-4-yl)azo]benzoato(2-)]chromate(1-)
- Molecular formula: C34H24CrN8O6.Li
- Molecular weight: 699.5506 g/mole
- Smiles : [Li+].CC1=NN(C(=O)C1\2[Cr-]3(OC(=O)c4c(cccc4)/N=N/C35C(=O)N(N=C5C)c6ccccc6)OC(=O)c7c(cccc7)/N=N2)c8ccccc8
- InChl: 1S/2C17H13N4O3.Cr.Li/c2*1-11-15(16(22)21(20-11)12-7-3-2-4-8-12)19-18-14-10-6-5-9-13(14)17(23)24;;/h2*2-10H,1H3,(H,23,24);;/q;;2*+1/ p-2/b2*19-18+;;
- Substance type: Organic
- Physical state: Solid

Species:

guinea pig

Strain:

Hartley

Sex:

female

Details on test animals and environmental conditions:

no data available

Route:

intradermal and epicutaneous

Vehicle:

not specified

Adequacy of induction:

not specified

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

not specified

Adequacy of challenge:

not specified

No. of animals per dose:

10

Details on study design:

no data available

Challenge controls:

no data available

Positive control substance(s):

not specified

Reading:

1st reading

Group:

test chemical

Clinical observations:

no reactions observed

Remarks on result:

no indication of skin sensitisation

The prediction was based on dataset comprised from the following descriptors: "Skin Sensitisation"
Estimation method: Takes mode 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 "i" )  and ("j" and "k" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as SN1 AND SN1 >> Nitrenium Ion formation AND SN1 >> Nitrenium Ion formation >> Aromatic azo AND SN1 >> Nitrenium Ion formation >> Unsaturated heterocyclic azo by DNA binding by OECD

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as AN2 AND AN2 >> Michael addition to activated double bonds in heterocyclic ring systems AND AN2 >> Michael addition to activated double bonds in heterocyclic ring systems >> Pyrazolone and Pyrazolidine Derivatives AND AN2 >> Schiff base formation with carbonyl compounds (AN2) AND AN2 >> Schiff base formation with carbonyl compounds (AN2) >> Pyrazolone and Pyrazolidine Derivatives AND Schiff base formation AND Schiff base formation >> Schiff base on pyrazolones and pyrazolidinones AND Schiff base formation >> Schiff base on pyrazolones and pyrazolidinones >> Pyrazolones and Pyrazolidinones by Protein binding by OASIS v1.4

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Acylation AND Acylation >> Direct Acylation Involving a Leaving group AND Acylation >> Direct Acylation Involving a Leaving group >> Acetates by Protein binding by OECD

Domain logical expression index: "d"

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

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Non binder, impaired OH or NH2 group OR Non binder, non cyclic structure OR Non binder, without OH or NH2 group OR Strong binder, NH2 group OR Strong binder, OH group OR Very strong binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "f"

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

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Alkaline Earth OR Halogens by Groups of elements

Domain logical expression index: "h"

Similarity boundary:Target: [Li]{+}.[Cr]{-}12(C3(C(C)=NN(c4ccccc4)C3=O)N=Nc3ccccc3C(=O)O1)C1(C(C)=NN(c3ccccc3)C1=O)N=Nc1ccccc1C(=O)O2
Threshold=10%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "i"

Similarity boundary:Target: [Li]{+}.[Cr]{-}12(C3(C(C)=NN(c4ccccc4)C3=O)N=Nc3ccccc3C(=O)O1)C1(C(C)=NN(c3ccccc3)C1=O)N=Nc1ccccc1C(=O)O2
Threshold=40%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "j"

Parametric boundary:The target chemical should have a value of log Kow which is >= 3

Domain logical expression index: "k"

Parametric boundary:The target chemical should have a value of log Kow which is <= 7.53

Interpretation of results:

other: not sensitizing

Conclusions:

Lithium bis[2-[(4,5-dihydro-3-methyl-5-oxo-1-phenyl-1H-pyrazol-4-yl)azo]benzoato(2-)]chromate(1-) was predicted to be non sensitizing to the skin of female Hartley guinea pigs.

Executive summary:

The skin sensitization potential of lithium bis[2-[(4,5-dihydro-3-methyl-5-oxo-1-phenyl-1H-pyrazol-4-yl)azo]benzoato(2-)]chromate(1-) was estimated by SSS (2018) using OECD QSAR toolbox v3.4 with log kow as the primary descriptor. Lithium bis[2-[(4,5-dihydro-3-methyl-5-oxo-1-phenyl-1H-pyrazol-4-yl)azo]benzoato(2-)]chromate(1-) was predicted to be non sensitizing to the skin of female Hartley guinea pigs.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Skin Sensitization:

Various studies have been investigated to ascertain the degree of dermal sensitization caused by Lithium bis[2-[(4,5-dihydro-3-methyl-5-oxo-1-phenyl-1H-pyrazol-4-yl)azo]benzoato(2-)]chromate(1-) on living organisms. The studies are based on in vivo experiments in guinea pigs, humans along with predicted data for target chemical and its structurally similar read across chemicals,2-{2-[2-chloro-4-(3-chloro-4-{2-[2-oxo-1-(phenylcarbamoyl)propyl]diazen-1-yl}phenyl)phenyl]diazen-1-yl}-3-oxo-N-phenylbutanamide(C.I. Pigment Yellow 12)[CAS: 6358-85-6] and Chromium(3+) ion hydrogen bis([(6E)-6-{2-[(4Z)-3-methyl-5-oxo-1-phenyl-4 ,5-dihydro-1H-pyrazol-4-ylidene]hydrazin-1 -ylidene}cyclohexa-2,4-dien-1- ylidene]methanebis(olate)) (Acid yellow 121) [CAS:5601-29-6].The predicted data using the OECD QSAR toolbox has also been compared with the experimental data.

The skin sensitization potential of lithium bis[2-[(4,5-dihydro-3-methyl-5-oxo-1-phenyl-1H-pyrazol-4-yl)azo]benzoato(2-)]chromate(1-) was estimated by SSS (2018) using OECD QSAR toolbox v3.4 with log kow as the primary descriptor. Lithium bis[2-[(4,5-dihydro-3-methyl-5-oxo-1-phenyl-1H-pyrazol-4-yl)azo]benzoato(2-)]chromate(1-) was predicted to be non sensitizing to the skin of female Hartley guinea pigs.

This result is supported by the experimental study performed by Thierbach MA et.al (Contact Dermatitis, 1992, 27, 22-26), for the structurally similar read across chemical,2-{2-[2 -chloro-4-(3-chloro-4-{2-[2-oxo-1-(phenylcarbamoyl)propyl]diazen-1-yl}phenyl)phenyl]diazen-1-yl}-3-oxo-N-phenylbutanamide(C.I. Pigment Yellow 12)[CAS: 6358-82-6]. A group of 32 patients with p-aminoazobenzene allergy were presumed that an increase in color printed newspapers might cause dermatitis. Patch tests were performed using the azo dyes in the printed papers along with specimens of the colored-printed newspaper. The test group consisted for 20 women and 12 men. 30 patients with an allergic contact dermatitis but negative to p-aminoazobenzene and PPD were also tested with the same patch test series.

The dyes were kindly provided by the firms Hoechst and Ciba-Geigy. To avoid false-negative reactions, a test concentration of 2% in white petrolatum was chosen. Patch tests were performed using uniform patches and following Standard procedures.

C.I. Pigment Yellow 12 did not elicit a positive patch test reaction in any of the 32 patients positive to p-aminoazobenzene, nor in the 30 control volunteers

Hence, C.I Pigment Yellow 12 can be considered to be not sensitizing to skin.

The above studies are supported by the experimental study summarized in Scientific Committee on Cosmetology (seventh series), 1988; for the structurally similar read across chemical, Chromium(3+) ion hydrogen bis([(6E)-6-{2-[(4Z)-3-methyl-5-oxo-1-phenyl-4 ,5-dihydro-1H-pyrazol-4-ylidene]hydrazin-1 -ylidene}cyclohexa-2,4-dien-1- ylidene]methanebis(olate)) (Acid yellow 121) [CAS:5601-29-6].

The test material in induction treatment was subjected onto the skin of guinea pig by intra-cutaneous injections of 0.1 ml of 0.1 % aqueous solution three times per day for 5 successive days followed by one intracutaneous challenge injection of the same solution after 4 weeks of induction treatment. Chromium(3+) ion hydrogen bis([(6E)-6-{2-[(4Z)-3-methyl-5-oxo-1-phenyl-4 ,5-dihydro-1H-pyrazol-4-ylidene]hydrazin-1 -ylidene}cyclohexa-2,4-dien-1- ylidene]methanebis(olate))  didnot induce any dermal sensitization reactions in guinea pigs. Hence, Chromium(3+) ion hydrogen bis([(6E)-6-{2-[(4Z)-3-methyl-5-oxo-1-phenyl-4 ,5-dihydro-1H-pyrazol-4-ylidene]hydrazin-1 -ylidene}cyclohexa-2,4-dien-1- ylidene]methanebis(olate))  can be considered to be not sensitizing to skin.

Based on the available data for the target chemical as well as its structurally similar read across chemicals, and applying the weight of evidence approach, Lithium bis[2-[(4,5-dihydro-3-methyl-5-oxo-1-phenyl-1H-pyrazol-4-yl)azo]benzoato(2-)]chromate(1-) can be considered to be not sensitizing to skin. Comparing the above annotations with the criteria of CLP regulation, test chemical can be classified under the category “Not Classified”.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Available data for the target chemical, Lithium bis[2-[(4,5-dihydro-3-methyl-5-oxo-1-phenyl-1H-pyrazol-4-yl)azo]benzoato(2-)]chromate(1-) suggests that it is not likely to cause any dermal sensitization to skin.

Lithium bis[2-[(4,5-dihydro-3-methyl-5-oxo-1-phenyl-1H-pyrazol-4-yl)azo]benzoato(2-)]chromate(1-) can be considered to be not sensitizer to skin and can be classified under the category “Not Classified” as per CLP regulation.