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Description of key information

Data available for the structurally and functionally similar read across chemicals has been reviewed to determine the skin sensitization potential of the test chemical Reaction mass of Methylium, tris[4-(diethylamino)phenyl]- & acetate. The studies are as mentioned below:

 

Skin sensitization study for read across chemical was conducted by peer reviewed journal 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. After a rest period of two weeks, in challenge phase the right flank of each guinea pig was shaved and exposed to three different concentration10.0%, 5.0%, and 2.5%.Twenty-four hours after the last induction and challenge application, the animals were depilated to clearly observe dermal reactions. No erythema/edema was observed after application of test material .The test result was observed to be negative for the test substance. Therefore the test chemical was considered to be not sensitizing to the skin of guinea pig using modified Buehler and Klecak method for open Epicutaneous testing.

 

The above result was further supported by the skin sensitization study of another read across substance reported by safety assessment report on guinea pigs to determine its skin sensitizing potential. The induction involved 10 topical treatments of a 25% aqueous solution and 2 intradermal injections of 0.1 ml Freund's complete adjuvant in a period of 3 weeks. After a rest period of 12 days, animals were challenged with 0.5 mL of the 25% aqueous solution of test chemical and observed for skin reaction. The chemical did not provoke any sign of sensitization as judged from oedema formation and histopathological examination. Also Erythema could not be examined due to the colorant. Thus on the basis of observed effects, the test chemical was considered to be not sensitizing to the skin of guinea pigs.

 

Based on the above summarized studies for target chemical Reaction mass of Methylium, tris[4-(diethylamino)phenyl]- & acetate and its structurally and functionally similar read across substances,it can be concluded that the testchemical 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”.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Remarks:
experimental data of read across substances
Justification for type of information:
Data for the target chemical is summarized based on the structurally and functionally similar read across chemicals
Reason / purpose:
read-across source
Reason / purpose:
read-across source
Qualifier:
according to
Guideline:
other: as mentioned below
Principles of method if other than guideline:
WoE report is based on 2 skin sensitization studies as- WoE-2 and WoE-3. Skin sensitization of test chemical was determined by performing tests on guinea pigs.
GLP compliance:
not specified
Type of study:
other: 1.open epicutaneous test 2.guinea pig maximisation test
Justification for non-LLNA method:
not specified
Specific details on test material used for the study:
IUPAC name: Reaction mass of Methylium, tris[4-(diethylamino)phenyl]- & acetate Molecular weight: 515.7375Molecular formula: C33H45N3O2Smiles: CCN(CC)c1ccc(C{+}(c2ccc(N(CC)CC)cc2)(c2ccc(N(CC)CC)cc2).O{-}C(C)=O)cc1Inchl: 1S/C31H42N3.C2H4O2/c1-7-32(8-2)28-19-13-25(14-20-28)31(26-15-21-29(22-16-26)33(9-3)10-4)27-17-23-30(24-18-27)34(11-5)12-6;1-2(3)4/h13-24H,7-12H2,1-6H3;1H3,(H,3,4)/q+1;/p-1Physical state: Solid and liquidForm: Organic
Species:
guinea pig
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
No data available.
Route:
other: 1.epicutaneous, open
Vehicle:
propylene glycol
Concentration / amount:
10%
Day(s)/duration:
3 weeks
Adequacy of induction:
not specified
Route:
other: 2.intradermal and epicutaneous
Vehicle:
other: aqueous solution
Concentration / amount:
Intradermal concentration: 0.1 ml Freund'scomplete adjuvanttopical concentration: 25%
Day(s)/duration:
3 weeks
Adequacy of induction:
not specified
Route:
other: 1.epicutaneous, open
Vehicle:
propylene glycol
Concentration / amount:
10.0%, 5.0%, and 2.5%
Day(s)/duration:
48 hours
Adequacy of challenge:
not specified
Route:
other: 2.epicutaneous, occlusive
Vehicle:
other: aqueous solution
Concentration / amount:
25% (0.5ml)
Day(s)/duration:
not specified
Adequacy of challenge:
not specified
No. of animals per dose:
1.10 animals 2.Not specified
Details on study design:
1.Details on study designMAIN STUDYA. INDUCTION EXPOSURE- No. of exposures: 9- Exposure period:48 hour - Test groups: 10- Control group: no data - Site: the left flanks of ten albino guinea pigs were shavedand the test material applied three timesweekly( Monday,Wednesday,Friday)for three consecutiv weeeks. Each animal received 0.1 ml of the dye test material over a 1.8-cm circular area.- Frequency of applications: three times weekly (Monday, Wednesday Friday) for three consecutive weeks.- Duration: 3 weeks - Concentrations:10%B. CHALLENGE EXPOSURE- No. of exposures:1- Day(s) of challenge: Two week rest period - Exposure period: 24 hour - Test groups: 10- Control group: No data available.- Site: right flank of each guinea pig was shaved and test material applied on it.- Concentrations: 10.0%, 5.0%, and 2.5%- Evaluation (hr after challenge): 24 hour and 48 hours post-applicationOther – 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.2.MAIN STUDYA. INDUCTION EXPOSURE- No. of exposures: 12 (2 intradermal and 10 topical)- Exposure period: not specified- Test groups: no data- Control group: no data - Site: no data - Frequency of applications: no data- Duration: 3 weeks- Concentrations: 25%B. CHALLENGE EXPOSURE- No. of exposures:1- Day(s) of challenge: after 12 days- Exposure period: no data- Test groups: no data- Control group: no data- Site: no data- Concentrations: 25% (0.5ml)- Evaluation (hr after challenge): no data
Challenge controls:
No data available.
Positive control substance(s):
yes
Remarks:
1.DNCB (2,4-dinitrochlorobenze) 2.Not specified
Positive control results:
1.The positive DNCB (2,4-dinitrochlorobenze) control at the 0.5% induction /challenge concentration elicited positive response in all animals tested.2.Not specified
Reading:
other: 1.1st reading
Hours after challenge:
48
Group:
test group
Dose level:
10.0%, 5.0%, and 2.5%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No skin sensitization reaction observed.
Remarks on result:
no indication of skin sensitisation
Reading:
other: 2.1st reading
Group:
test group
Dose level:
25% (0.5ml)
No. with + reactions:
0
Clinical observations:
The chemical did not provoke any sign of sensitization.
Remarks on result:
no indication of skin sensitisation
Cellular proliferation data / Observations:
1. No indication of skin sensitization observed.2.The chemical did not provoke any sign of sensitization.
Interpretation of results:
other: not sensitising
Conclusions:
The test chemical Reaction mass of Methylium, tris[4-(diethylamino)phenyl]- & acetate was considered to be not sensitizing to the skin of guinea pigs.
Executive summary:

Data available for the structurally and functionally similar read across chemicals has been reviewed to determine the skin sensitization potential of the test chemical Reaction mass of Methylium, tris[4-(diethylamino)phenyl]- & acetate. The studies are as mentioned below:

 

Skin sensitization study for read across chemical was conducted by peer reviewed journal 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. After a rest period of two weeks, in challenge phase the right flank of each guinea pig was shaved and exposed to three different concentration10.0%, 5.0%, and 2.5%.Twenty-four hours after the last induction and challenge application, the animals were depilated to clearly observe dermal reactions. No erythema/edema was observed after application of test material .The test result was observed to be negative for the test substance. Therefore the test chemical was considered to be not sensitizing to the skin of guinea pig using modified Buehler and Klecak method for open Epicutaneous testing.

 

The above result was further supported by the skin sensitization study of another read across substance reported by safety assessment report on guinea pigs to determine its skin sensitizing potential. The induction involved 10 topical treatments of a 25% aqueous solution and 2 intradermal injections of 0.1 ml Freund's complete adjuvant in a period of 3 weeks. After a rest period of 12 days, animals were challenged with 0.5 mL of the 25% aqueous solution of test chemical and observed for skin reaction. The chemical did not provoke any sign of sensitization as judged from oedema formation and histopathological examination. Also Erythema could not be examined due to the colorant. Thus on the basis of observed effects, the test chemical was considered to be not sensitizing to the skin of guinea pigs.

 

Based on the above summarized studies for target chemical Reaction mass of Methylium, tris[4-(diethylamino)phenyl]- & acetate and its structurally and functionally similar read across substances,it can be concluded that the testchemical 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”.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Data available for the structurally and functionally similar read across chemicals has been reviewed to determine the skin sensitization potential of the test chemical Reaction mass of Methylium, tris[4-(diethylamino)phenyl]- & acetate. The studies are as mentioned below:

 

Skin sensitization study for read across chemical was conducted by peer reviewed journal 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. After a rest period of two weeks, in challenge phase the right flank of each guinea pig was shaved and exposed to three different concentration10.0%, 5.0%, and 2.5%.Twenty-four hours after the last induction and challenge application, the animals were depilated to clearly observe dermal reactions. No erythema/edema was observed after application of test material .The test result was observed to be negative for the test substance. Therefore the test chemical was considered to be not sensitizing to the skin of guinea pig using modified Buehler and Klecak method for open Epicutaneous testing.

 

The above result was further supported by the skin sensitization study of another read across substance reported by safety assessment report on guinea pigs to determine its skin sensitizing potential. The induction involved 10 topical treatments of a 25% aqueous solution and 2 intradermal injections of 0.1 ml Freund's complete adjuvant in a period of 3 weeks. After a rest period of 12 days, animals were challenged with 0.5 mL of the 25% aqueous solution of test chemical and observed for skin reaction. The chemical did not provoke any sign of sensitization as judged from oedema formation and histopathological examination. Also Erythema could not be examined due to the colorant. Thus on the basis of observed effects, the test chemical was considered to be not sensitizing to the skin of guinea pigs.

 

Based on the above summarized studies for target chemical Reaction mass of Methylium, tris[4-(diethylamino)phenyl]- & acetate and its structurally and functionally similar read across substances,it can be concluded that the testchemical 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 Reaction mass of Methylium, tris[4-(diethylamino)phenyl]- & acetate and its structurally and functionally similar read across substanceswere observed in various studies. From the results obtained from these studies it is concluded that the chemical Reaction mass of Methylium, tris[4-(diethylamino)phenyl]- & acetate is not likely to cause skin sensitization and hence can be classified as non-skin sensitizer.