p,p',p''-tris(diethylamino)trityl alcohol

Endpoint summary

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:

The supporting QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: Prediction is done using QSAR Toolbox version 3.4

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.4

GLP compliance:

no

Type of study:

Buehler 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): Benzenemethanol, 4-(diethylamino)- alpha, alpha -bis 4-(diethylamino)phenyl -
Molecular formula:C31H43N3O
Molecular weight: 473.71g/mol
Smiles notation: OC(c(ccc(N(CC)CC)c1)c1)(c(ccc(N(CC)CC)c2)c2)c(ccc(N(CC)CC)c3)c3
Substance type: Organic
Physical State: Solid

Details on the study design:

not specified

Details on the study design:

not specified

Species:

guinea pig

Strain:

Hartley

Sex:

not specified

Details on test animals and environmental conditions:

not specified

Route:

epicutaneous, occlusive

Vehicle:

not specified

Concentration / amount:

not specified

Day(s)/duration:

48h

Adequacy of induction:

not specified

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

not specified

Concentration / amount:

not specified

Day(s)/duration:

48h

Adequacy of challenge:

not specified

No. of animals per dose:

10

Details on study design:

not specified

Challenge controls:

not specified

Positive control substance(s):

not specified

Vehicle:

not specified

Concentration:

not specified

No. of animals per dose:

10

Details on study design:

not specified

Positive control substance(s):

not specified

Reading:

1st reading

Group:

test chemical

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

not sensitising

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 7 nearest neighbours
Domain  logical expression:Result: In Domain

((("a" or "b" or "c" or "d") and("e" and(not "f")) ) and("g" and "h") )

Domain logical expression index: "a"

Referential boundary:The target chemical should be classified as Aliphatic Carbon [CH] AND Aliphatic Carbon [-CH2-] AND Aliphatic Carbon [-CH3] AND Aliphatic Nitrogen, one aromatic attach [-N] AND Amino, aliphatic attach [-N<] AND Aromatic Carbon [C] AND Olefinic carbon [=CH- or =C<] by Organic functional groups (US EPA)

Domain logical expression index: "b"

Referential boundary:The target chemical should be classified as Amine AND Anion AND Aromatic compound AND Cation AND Tertiary amine AND Tertiary mixed amine by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "c"

Referential boundary:The target chemical should be classified as Alkene AND Ammonium salt AND Aromatic amine AND Aryl by Organic Functional groups

Domain logical expression index: "d"

Referential boundary:The target chemical should be classified as Alkene AND Ammonium salt AND Aromatic amine AND Overlapping groups by Organic Functional groups (nested)

Domain logical expression index: "e"

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

Domain logical expression index: "f"

Referential boundary:The target chemical should be classified as AN2 OR AN2 >>  Michael-type addition, quinoid structures OR AN2 >>  Michael-type addition, quinoid structures >> Quinones and Trihydroxybenzenes OR AN2 >> Schiff base formation by aldehyde formed after metabolic activation OR AN2 >> Schiff base formation by aldehyde formed after metabolic activation >> Geminal Polyhaloalkane Derivatives OR Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> Amino Anthraquinones OR Non-covalent interaction >> DNA intercalation >> Quinones and Trihydroxybenzenes OR Radical OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Amino Anthraquinones OR Radical >> Radical mechanism via ROS formation (indirect) >> Geminal Polyhaloalkane Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> Quinones and Trihydroxybenzenes OR SN1 OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Amino Anthraquinones OR SN2 OR SN2 >> Acylation involving a leaving group after metabolic activation OR SN2 >> Acylation involving a leaving group after metabolic activation >> Geminal Polyhaloalkane Derivatives OR SN2 >> Nucleophilic substitution at sp3 carbon atom after thiol (glutathione) conjugation OR SN2 >> Nucleophilic substitution at sp3 carbon atom after thiol (glutathione) conjugation >> Geminal Polyhaloalkane Derivatives by DNA binding by OASIS v.1.4

Domain logical expression index: "g"

Parametric boundary:The target chemical should have a value of log Kow which is >= 2.56

Domain logical expression index: "h"

Parametric boundary:The target chemical should have a value of log Kow which is <= 7.1

Interpretation of results:

other: not sensitising

Conclusions:

The substance Benzenemethanol, 4-(diethylamino)-alpha,alpha-bis(4-(diethylamino)phenyl)- (CAS No: 596-49-6) is estimated to be not sensitizing to skin of Hartley guinea pig.

Executive summary:

The skin sensitization for Benzenemethanol, 4-(diethylamino)-alpha,alpha-bis(4-(diethylamino)phenyl)- (CAS No: 596-49-6)is estimated using OECD QSAR toolbox version 3.4. The test substance Benzenemethanol, 4-(diethylamino)-alpha,alpha-bis(4-(diethylamino)phenyl)- (CAS No: 596-49-6) is estimated to be not sensitizing to skin of Hartley guinea pig.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Skin sensitization

Skin sensitization behaviour of test compound Benzenemethanol, 4-(diethylamino)-alpha,alpha-bis(4-(diethylamino)phenyl)- (CAS No: 596-49-6)have been summarized below by using data from prediction model based estimation and its read across substances.

OECD QSAR toolbox version 3.4 estimated the skin sensitization potential of test chemical Benzenemethanol, 4-(diethylamino)-alpha, alpha-bis(4-(diethylamino)phenyl)- (CAS No: 596-49-6) by Buehler test on Hartley guinea pigs. According to this prediction model, the test chemical failed to induce skin sensitization in guinea pigs. Thus the test compound Benzenemethanol, 4-(diethylamino)-alpha,alpha-bis(4-(diethylamino)phenyl)- (CAS No: 596-49-6) is estimated to be non-sensitizing to skin of Hartley guinea pigs.

The skin sensitization study was conducted by JOE DINARDO, Raleigh N, C; and ZOE DIANA DRAELOS in 2007 to observe the skin effects of similar read across substanceBasic violet 3 (CAS No:548-62-9). This test was carried out in guinea pig using modified Buehler and Klecak method for open Epicutaneous testing. For the induction phase, the left flanks of 10 albino guinea pigs were shaved and the dye test material applied three times weekly (Monday, Wednesday Friday) for three consecutive weeks. Each animal received 0.1 ml of the dye test material over a 1.8-cm circular area. Following the induction period, the guinea pigs entered the challenge phase. The challenge phase began after a two-week rest period when the right flank of each guinea pig was shaved and exposed to three different dye test material concentration (100%,50%, and 25% of the induction concentration).Twenty-four hours after the last induction and challenge application, the animals were depilated to clearly observe dermal reactions. The test sites were graded for erythema and edema 24 and 48 hours post-application using a four-point ordinal scale (0 = no reaction, 1 -- slight reaction, 2 = moderate reaction, 3 = severe reaction. A positive reaction was defined as an erythema/edema value during the challenge phase of at least one skin grade higher than during the last induction phase. No erythema/edema was observed after 24 and 48 hours post-application. Hence the test substance Basic violet 3(CAS No: 548-62-9) was considered as not sensitizing to the guinea pigs skin.

Local Lymph Node Assay was conducted on CBA/J female mice (50) byOPINION OF THE SCIENTIFIC COMMITTEE ON COSMETIC PRODUCTS AND NON-FOOD PRODUCTS (SCCNFP) 2004foranother similar read across substance Brilliant blue(CAS No: -3844-45-9) in accordance withOECD guideline 429to assess its sensitization potential. In this assay, on days 0, 1 and 2 the animals received 25 μl of one of the test preparations or vehicle on the dorsal surface of each ear. On day 5 all mice received intravenous injection of tritium labeled thymidine in phosphate buffered saline, and 5 hours later they were killed humanely and the draining auricular lymph nodes were removed. Single cell suspensions were prepared for each animal, appropriately treated and measured by liquid scintillation counting. The stimulation indices were less than 3 at all tested concentrations, hence an EC3 value could not be calculated. Hence the test chemical Brilliant blue(CAS No: -3844-45-9) was considered to be non-sensitizing inLocal Lymph Node Assay.

Thus the available data estimated by prediction model for target substance Benzenemethanol, 4-(diethylamino)-alpha,alpha-bis(4-(diethylamino)phenyl)- (CAS No: 596-49-6) as well as available data for read across substancesBasic violet 3 (CAS No:548-62-9)and Brilliant blue(CAS No: -3844-45-9) and applying weight of evidence approach suggests that the test chemical substance Benzenemethanol, 4-(diethylamino)-alpha,alpha-bis(4-(diethylamino)phenyl)- (CAS No: 596-49-6) is not likely to cause skin sensitization and thus can be classified as non-skin sensitizer.

Migrated from Short description of key information:

OECD QSAR toolbox version 3.4 estimated the skin sensitization potential of test chemical Benzenemethanol, 4-(diethylamino)-alpha, alpha-bis(4-(diethylamino)phenyl)- (CAS No: 596-49-6) by Buehler test on Hartley guinea pigs. According to this prediction model, the test chemical failed to induce skin sensitization in guinea pigs. Thus the test compound Benzenemethanol, 4-(diethylamino)-alpha,alpha-bis(4-(diethylamino)phenyl)- (CAS No: 596-49-6) is estimated to be non-sensitizing to skin of Hartley guinea pigs.

Justification for selection of skin sensitisation endpoint:

The substance Benzenemethanol, 4-(diethylamino)-alpha,alpha-bis(4-(diethylamino)phenyl)- (CAS No: 596-49-6) is estimated to be not sensitizing   to skin of Hartley guinea pig.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

The skin sensitization potential of test chemical substance Benzenemethanol, 4-(diethylamino)-alpha,alpha-bis(4-(diethylamino)phenyl)- (CAS No: 596-49-6)and its read acrosssubstancesBasic violet 3 (CAS No:548-62-9)and Brilliant blue(CAS No: -3844-45-9) were observed in various studies. From the results obtained from these studies it is concluded that the chemical substance Benzenemethanol, 4-(diethylamino)-alpha, alpha-bis(4-(diethylamino)phenyl)- (CAS No: 596-49-6) was unable to cause skin sensitization and hence can be classified as non-skin sensitizing.