Diphenyl sulphide

Endpoint summary

Description of key information

The skin sensitization potential of target chemical 1,4-bis[(2-methylphenyl)amino]anthraquinone (CAS No: 6737-68-4) was assessedin various experimental studies which were conducted on guinea for target chemical1,4-bis[(2-methylphenyl)amino]anthraquinone (CAS No: 6737-68-4) andits structurally similar read across substancesDisperse violet 4 (CAS No:1220-94-6)andSudan III (CAS No: 85-86-9). The predicted data usingQSAR toolboxhas also been compared with the experimental data.Based on the available data for the target and read across substances and applying the weight of evidence approach, it can be concluded that chemical 1,4-bis[(2-methylphenyl)amino]anthraquinone (CAS No: 6737-68-4) is unable to cause skin sensitization and thus can be considered as not sensitizing. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

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 the supporting QMRF report has been attached.

Qualifier:

no guideline available

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.3 with respect to the descriptor log Kow.

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 (as cited in study report): Diphenyl sulphide
Molecular formula:C12H10S
Molecular weight:186.277 g/mol
Substance Type: Organic
Physical State: Liquid

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

female

Details on test animals and environmental conditions:

No data available

Route:

intradermal and epicutaneous

Vehicle:

not specified

Concentration / amount:

No data

Day(s)/duration:

No data

Adequacy of induction:

not specified

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

not specified

Concentration / amount:

no data

Day(s)/duration:

48 hours

Adequacy of challenge:

not specified

No. of animals per dose:

20 females

Details on study design:

no data available

Challenge controls:

no data available

Positive control substance(s):

not specified

Reading:

1st reading

Hours after challenge:

48

Group:

test chemical

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

No reactions was 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" 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 "n" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Aryl AND Sulfide by Organic Functional groups

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Aryl AND Overlapping groups AND Sulfide by Organic Functional groups (nested)

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Aliphatic Sulfur, two aromatic attach AND Aromatic Carbon [C] AND Olefinic carbon [=CH- or =C<] by Organic functional groups (US EPA)

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Aromatic compound AND Thioether by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OECD

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Michael addition OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Alkyl phenols OR SN1 OR SN1 >> Iminium Ion Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines OR SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >> Aromatic azo OR SN1 >> Nitrenium Ion formation >> Primary aromatic amine by DNA binding by OECD

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Not possible to classify according to these rules by DPRA Cysteine peptide depletion

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as High reactive OR High reactive >> Activated haloarenes by DPRA Cysteine peptide depletion

Domain logical expression index: "i"

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

Domain logical expression index: "j"

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

Domain logical expression index: "k"

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

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Direct acylation involving a leaving group OR Acylation >> Direct acylation involving a leaving group >> Carbamates  OR Acylation >> Ester aminolysis OR Acylation >> Ester aminolysis >> Dithiocarbamates by Protein binding by OASIS v1.3

Domain logical expression index: "m"

Parametric boundary:The target chemical should have a value of log Kow which is >= 3.32

Domain logical expression index: "n"

Parametric boundary:The target chemical should have a value of log Kow which is <= 5.79

Interpretation of results:

other: not sensitizing

Conclusions:

The substance, Diphenyl sulphide (CAS No. 139-66-2) was predicted to be non sensitising to the skin of guinea pigs.

Executive summary:

The skin sensitization potential of Diphenyl sulphide (CAS No. 139 -66 -2) was estimated by using OECD QSAR toolbox v3.3 with log kow as the primary descriptor and considering the five closest read across substances. No skin reactions indicative of sensitisation were predicted. Thus, the substance Diphenyl sulphide (CAS No. 139-66-2) was predicted to be non sensitizing to the skin of guinea pigs.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Various studieshas been investigated for the test chemicalDiphenyl sulphide (CAS No. 139 -66 -2)  to observe the potential for skin sensitization to a greater or lesser extent. The studies are based on in vivo experiments in guinea pigs and humans for target chemicalDiphenyl sulphide (CAS No. 139 -66 -2)  and its structurally similar read across substancesDiphenyl ether (CAS no:101-84-8), Biphenyl (CAS no: 92-52-4) and Dimethyl disulphide (CAS No. 624-92-0). 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 Diphenyl sulphide (CAS No. 139 -66 -2)  was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor. Diphenyl sulphide (CAS No. 139 -66 -2)  was estimated to be not sensitizing to the skin of Dunkin-Hartley guinea pigs. Based on the estimated result Diphenyl sulphide (CAS No. 139 -66 -2)  can be considered to be not sensitizing to Dunkin-Hartley guinea pigs.

 

 

The International Programme on Chemical Safety (IPCS)-INCHEM {Biphenyl; Concise International Chemical Assessment Document 6; Joint FAO/WHO Expert Committee on Food Additives; 1999} conducted Guinea pig maximization test for chemical Biphenyl (CAS no: 92-52-4) in accordance with OECD Guideline 406. Since the chemical did not induce any signs of contact sensitization, Biphenyl (CAS no: 92-52-4) was considered to be not sensitizing to the guinea pigs’ skin.

 

The HSDB {U.S. National Library of Medicine National Institutes of Health, Health & Human Services; 2017} conducted a human maximization test was for Diphenyl ether (CAS no:101-84-8) under occlusive condition that supported the above mentioned result.The test material was mixed into petrolatum N.F. at 4% concentration and applied to the same forearm sites under occlusion for five alternate-day 48-hour periods. Each application of the test material was preceded by treatment of the patch site with 5% aqueous sodium lauryl sulfate under occlusion.Following a ten day rest period challenge patches of the test material were applied to fresh sites on the scapular backs under occlusion for 48 hours. The challenge sites were pretreated for one hour with 10% aqueous sodium lauryl sulfate. Clinical evaluations were made at 48 and 72 hours. Diphenyl oxide did not produce any cases of contact allergy. Therefore,Diphenyl ether (CAS no:101-84-8) was considered to be not sensitizing to the human skin in human maximization test.

 

The above results were further supported by the experimental study reported by U.S. Environmental Protection Agency {High Production Volume (HPV) Challenge Program; 2016} according to EPA-40 CFR 163-81-6 method on guinea pigs by Buehler test for read across chemical Dimethyl disulphide (CAS No. 624-92-0). 10 test group and 10 positive control groups were used in this study. In the preliminary screen, no erythema was observed at any of the concentrations of test material applied to the skin over a 48 hour period. The test material was therefore tested neat in the full scale sensitization study. After the initial and second challenge applications, the guinea pigs did not exhibit any erythema and were considered non - sensitized. Expected responses were noted in the positive control animals. The data validates the responsiveness of the guinea pigs to DNCB.  Thus, from the study it can be concluded that Dimethyl disulphide (CAS No. 624-92-0) is not a skin sensitizer in the guinea pigs in Buehler test.

 

Thus on the basis of available data for thetarget chemicalDiphenyl sulphide (CAS No. 139 -66 -2)  and its structurally similar read across substancesDiphenyl ether (CAS no:101-84-8), Biphenyl (CAS no: 92-52-4) and Dimethyl disulphide (CAS No. 624-92-0),it can be concluded thatchemical Diphenyl sulphide (CAS No. 139 -66 -2)  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 Diphenyl sulphide (CAS No. 139 -66 -2)   and its structurally similar read across substancesDiphenyl ether (CAS no:101-84-8), Biphenyl (CAS no: 92-52-4) and Dimethyl disulphide (CAS No. 624-92-0) were observed in various studies. From the results obtained from these studies it is concluded that the chemical Diphenyl sulphide (CAS No. 139 -66 -2)  is not likely to cause skin sensitization and hence can be classified as non-skin sensitizer.