4,4',4''-triaminotrityl alcohol

Endpoint summary

Description of key information

The skin sensitization potential of 4,4’,4’’-Triaminotrityl alcohol (CAS No: 467-62-9) was estimated using OECD QSAR toolbox version 3.4 with log Pow as the primary descriptor. The substance 4,4’,4’’-Triaminotrityl alcohol (CAS No: 467-62-9) was estimated to be not sensitizing to the skin of guinea pigs. Based on the estimated result 4,4’,4’’-Triaminotrityl alcohol (CAS No: 467-62-9) failed to induce skin sanitization effects and hence is considered to be not sensitizing to guinea pigs 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 3.4 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 3.4

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): 4,4',4''-Triaminotrityl alcohol
- Molecular formula: C19H19N3O
- Molecular weight: 305.379 g/mol
- Smiles notation: C(c1ccc(N)cc1)(c1ccc(N)cc1)(c1ccc(N)cc1)O
-InChl: 1S/C19H19N3O/c20-16-7-1-13(2-8-16)19(23,14-3-9-17(21)10-4-14)15-5-11-18(22)12-6-15/h1-12,23H,20-22H2
- Substance type: Organic
- Physical state: Solid

Species:

guinea pig

Strain:

not specified

Sex:

not specified

Details on test animals and environmental conditions:

not specified

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

Vehicle:

not specified

Concentration / amount:

No data available

Day(s)/duration:

No data available

Adequacy of challenge:

not specified

No. of animals per dose:

20

Details on study design:

No data available

Challenge controls:

No data available

Positive control substance(s):

not specified

Reading:

1st reading

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 mode value from the 6 nearest neighbours
Domain  logical expression:Result: In Domain

((((((((("a" or "b" or "c" or "d" or "e" or "f" )  and ("g" and ( not "h") )  )  and "i" )  and ("j" and ( not "k") )  )  and "l" )  and "m" )  and "n" )  and "o" )  and ("p" and "q" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Anilines (Acute toxicity) AND Dianilines by US-EPA New Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Radical AND Radical >> Radical mechanism via ROS formation (indirect) AND Radical >> Radical mechanism via ROS formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines AND SN1 AND SN1 >> Nucleophilic attack after nitrenium ion formation AND SN1 >> Nucleophilic attack after nitrenium ion formation >> Single-Ring Substituted Primary Aromatic Amines by DNA binding by OASIS v.1.4

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 >> Primary aromatic amine by DNA binding by OECD

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Strong binder, NH2 group by Estrogen Receptor Binding

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as AN2 AND AN2 >> Michael-type addition to quinoid structures  AND AN2 >> Michael-type addition to quinoid structures  >> Substituted Anilines by Protein binding by OASIS v1.4

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Anilines (Unhindered) AND Benzyl Alcohols by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as AN2 AND AN2 >> Michael-type addition to quinoid structures  AND AN2 >> Michael-type addition to quinoid structures  >> Substituted Anilines by Protein binding by OASIS v1.4

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Acylation involving an activated (glucuronidated) carboxamide group OR Acylation >> Acylation involving an activated (glucuronidated) carboxamide group >> Carboxylic Acid Amides OR Acylation >> Acylation involving an activated (glucuronidated) sulfonamide group OR Acylation >> Acylation involving an activated (glucuronidated) sulfonamide group >> Arenesulfonamides OR Acylation >> Direct acylation involving a leaving group OR Acylation >> Direct acylation involving a leaving group >> Carboxylic Acid Amides OR Acylation >> Ester aminolysis OR Acylation >> Ester aminolysis >> Amides OR AN2 >> Michael addition to activated double bonds OR AN2 >> Michael addition to activated double bonds >> alpha,beta-Unsaturated Carbonyls and Related Compounds OR AN2 >> Michael-type addition to quinoid structures  >> Carboxylic Acid Amides OR AN2 >> Michael-type addition to quinoid structures  >> N-Substituted Aromatic Amines OR AN2 >> Nucleophilic addition at polarized N-functional double bond OR AN2 >> Nucleophilic addition at polarized N-functional double bond >> Arenesulfonamides OR No alert found OR SN2 OR SN2 >> SN2 Reaction at a sp3 carbon atom OR SN2 >> SN2 Reaction at a sp3 carbon atom >> Activated alkyl esters and thioesters  OR SNAr OR SNAr >> Nucleophilic aromatic substitution on activated aryl and heteroaryl compounds OR SNAr >> Nucleophilic aromatic substitution on activated aryl and heteroaryl compounds >> Activated aryl and heteroaryl compounds by Protein binding by OASIS v1.4

Domain logical expression index: "i"

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

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as No alert found by DNA alerts for AMES by OASIS v.1.4

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Radical OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitroaniline Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR Radical >> Radical mechanism via ROS formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines OR SN1 OR SN1 >> Nucleophilic attack after nitrenium ion formation OR SN1 >> Nucleophilic attack after nitrenium ion formation >> Single-Ring Substituted Primary Aromatic Amines OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitroaniline Derivatives OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids by DNA alerts for AMES by OASIS v.1.4

Domain logical expression index: "l"

Similarity boundary:Target: Nc1ccc(C(O)(c2ccc(N)cc2)c2ccc(N)cc2)cc1
Threshold=30%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "m"

Similarity boundary:Target: Nc1ccc(C(O)(c2ccc(N)cc2)c2ccc(N)cc2)cc1
Threshold=10%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "n"

Similarity boundary:Target: Nc1ccc(C(O)(c2ccc(N)cc2)c2ccc(N)cc2)cc1
Threshold=40%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "o"

Similarity boundary:Target: Nc1ccc(C(O)(c2ccc(N)cc2)c2ccc(N)cc2)cc1
Threshold=80%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "p"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.668

Domain logical expression index: "q"

Parametric boundary:The target chemical should have a value of log Kow which is <= 2.47

Interpretation of results:

other: not sensitising

Conclusions:

The substance 4,4’,4’’-Triaminotrityl alcohol (CAS No: 467-62-9) was estimated to be not sensitizing to the skin of guinea pigs. Based on the estimated result 4,4’,4’’-Triaminotrityl alcohol (CAS No: 467-62-9) failed to induce skin sanitization effects and hence is considered to be not sensitizing to guinea pigs.

Executive summary:

The skin sensitization potential of 4,4’,4’’-Triaminotrityl alcohol (CAS No: 467-62-9) was estimated using OECD QSAR toolbox version 3.4 with log Pow as the primary descriptor. The substance 4,4’,4’’-Triaminotrityl alcohol (CAS No: 467-62-9) was estimated to be not sensitizing to the skin of guinea pigs. Based on the estimated result 4,4’,4’’-Triaminotrityl alcohol (CAS No: 467-62-9) failed to induce skin sanitization effects and hence is considered to be not sensitizing to 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 chemical4,4’,4’’-Triaminotrityl alcohol (CAS No: 467-62-9)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 chemical4,4’,4’’-Triaminotrityl alcohol (CAS No: 467-62-9) and its structurally similar read across substancesDapsone(CAS No: 80-08-0) and 2-Chloroaniline(CAS No: 95-51-2).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 4,4’,4’’-Triaminotrityl alcohol (CAS No: 467-62-9) was estimated using OECD QSAR toolbox version 3.4 with logPow as the primary descriptor. The substance 4,4’,4’’-Triaminotrityl alcohol (CAS No: 467-62-9) was estimated to be not sensitizing to the skin of guinea pigs. Based on the estimated result 4,4’,4’’-Triaminotrityl alcohol (CAS No: 467-62-9) can be considered to be not sensitizing to guinea pigs.

 

TheNational Technical Reports library (NTRL, 1991) conducted skin sensitization study forstructurally similar read across substance Dapsone(CAS No: 80-08-0) in guinea pigs.In a preliminary dose-range finding study, four animals (two males and two females) were exposed to one concentration (as received) of Dapsone at four skin sites. Based upon the results of the dose-range finding study, the dose chosen for induction was 100 %. Dapsone was dermally applied to twenty guinea pigs (ten males and ten females for a total of three six-hour insult periods at a 100 % concentration. An additional group of ten guinea pigs (five males and five females) was treated with 1-chloro-2,4-dinitrobenzene at 0.3% concentration for a total of three six-hour insult periods. Fourteen days after the last induction period, all animals were challenged at a naive site. A positive response was elicited in the animals receiving the positive control article, 1-chloro-2,4-dinitrobenzene (DNCB). Redness and edema scores in all animals at 24 and 48 h recorded after each treatment and at 24 and 48 h after the challenge. No positive responses were observed in guinea pig receiving dapsone at a 100 % concentration at 24 or 48 hours after the challenge. Dapsone did not cause hypersensitivity in guinea pigs. Hence Dapsone(CAS No: 80-08-0)is not sensitizer to the skin of Guinea pig.

 

The above results were further supported by theGuinea pig maximisation test reported by the INVENTORY MULTI-TIERED ASSESSMENT AND PRIORITISATION (IMAP) - NICNASA (2017) reportedin 20 guinea pigs (Bor:DHPW) forstructurally similar read across substance2-Chloroaniline(CAS No: 95-51-2) in accordance withOECD TG 406 (Skin sensitisation). During induction, each guinea pigs were intradermally induced with 5 % of 2-chloroaniline in propylene glycol (w/v) followed by topical treatment using occulusive patches with 0.5 mL neat 2-chloroaniline.Challenge phase was conducted with semiocclusive patch with 0.5 mL of neat 2-chloroaniline for 24 hours. Since no sensitization reactions were observed in control or in test group, the chemical 2-Chloroaniline(CAS No: 95-51-2) was considered to be not sensitizing to theskin of guinea pigs.

 

 

Thus on the basis of available data for the target chemical 4,4’,4’’-Triaminotrityl alcohol (CAS No: 467-62-9) and its structurally similar read across substancesDapsone(CAS No: 80-08-0) and 2-Chloroaniline(CAS No: 95-51-2),it can be concluded thatchemical 4,4’,4’’-Triaminotrityl alcohol (CAS No: 467-62-9) 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 4,4’,4’’-Triaminotrityl alcohol (CAS No: 467-62-9) and its structurally similar read across substances Dapsone(CAS No: 80-08-0) and 2-Chloroaniline(CAS No: 95-51-2) were observed in various studies. From the results obtained from these studies it is concluded that the chemical 4,4’,4’’-Triaminotrityl alcohol (CAS No: 467-62-9) is not likely to cause skin sensitization and hence can be classified as non skin sensitizer.