Registration Dossier

Administrative data

Description of key information

Based on the available data for the structurally similar read across substances and applying the weight of evidence approach, it can be concluded that the target chemical will also tend to behave in a similar that of the read across substances. Therefore,  Reaction mass of 3H-​Indolium, 2-​[[2-​(4-​methoxyphenyl)​-​2-​methylhydrazinyliden​e]​methyl]​-​1,​3,​3-​trimethyl-​ & acetate was estimated to be not sensitizing to skin.

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:
other: Weight of evidence approach based on structurally similar chemicals
Justification for type of information:
Weight of evidence approach based on structurally similar chemicals
Reason / purpose:
read-across: supporting information
Reason / purpose:
read-across: supporting information
Qualifier:
according to
Guideline:
other: Weight of evidence approach based on structurally similar chemicals
Principles of method if other than guideline:
The weight of evidence report has been prepared based on the read across substances identified based on structural and functional similarity to assess the dermal senstiization potential of Reaction mass of 3H-​Indolium, 2-​[[2-​(4-​methoxyphenyl)​-​2-​methylhydrazinyliden​e]​methyl]​-​1,​3,​3-​trimethyl-​ & acetate
GLP compliance:
not specified
Type of study:
other: Weight of evidence approach based on structurally similar chemicals
Specific details on test material used for the study:
- Name of test material: Reaction mass of 3H-​Indolium, 2-​[[2-​(4-​methoxyphenyl)​-​2-​methylhydrazinyliden​e]​methyl]​-​1,​3,​3-​trimethyl-​ & acetate- Molecular formula: C20H24N3OC2H3O2- Molecular weight: 381.473 g/mol- Smiles notation: [N+]=1(c2ccccc2C(C)(C)C1\C=N\NCc1ccc(cc1)OC)C.C(C)(=O)[O-]- InChl: 1S/C20H23N3O.C2H4O2/c1-20(2)17-7-5-6-8-18(17)23(3)19(20)14-22-21-13-15-9-11-16(24-4)12-10-15;1-2(3)4/h5-12,14H,13H2,1-4H3;1H3,(H,3,4)- Substance type: Organic- Physical state: Liquid (Yellow)
Species:
other: humans and guinea pigs
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
no data available
Route:
intradermal and epicutaneous
Vehicle:
water
Concentration / amount:
0.1
Day(s)/duration:
5
Adequacy of induction:
not specified
Route:
epicutaneous, occlusive
Vehicle:
petrolatum
Concentration / amount:
1%
Day(s)/duration:
24 hours
Adequacy of induction:
not specified
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
0.1 ml
Day(s)/duration:
1 days
Adequacy of challenge:
not specified
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
petrolatum
Concentration / amount:
1%
Day(s)/duration:
24 hours
Adequacy of challenge:
not specified
No. of animals per dose:
1.82. no data available
Details on study design:
The study is based on weight of evidence approach from the read across values
Challenge controls:
no data available
Positive control substance(s):
not specified
Reading:
1st reading
Group:
test group
Clinical observations:
no dermal reactions observed
Remarks on result:
no indication of skin sensitisation
Interpretation of results:
other: not sensitizing
Conclusions:
Based on the available data for the structurally similar read across substances and applying the weight of evidence approach, it can be concluded that the target chemical will also tend to behave in a similar that of the read across substances. Therefore, Reaction mass of 3H-​Indolium, 2-​[[2-​(4-​methoxyphenyl)​-​2-​methylhydrazinyliden​e]​methyl]​-​1,​3,​3-​trimethyl-​ & acetate was estimated to be not sensitizing to skin.
Executive summary:

Based on the available studies for the structurally similar read across chemicals, weight of evidence approach was applied to assess the dermal sensitization potential of  Reaction mass of 3H-​Indolium, 2-​[[2-​(4-​methoxyphenyl)​-​2-​methylhydrazinyliden​e]​methyl]​-​1,​3,​3-​trimethyl-​ & acetate

A study was performed in human volunteers to determine the degree of allergic reactions caused by the structurally similar read across chemical.

The test chemical 1% in petrolatum was applied onto the back of 8 healthy patients for 24 hours by using Finn Chambers® on Scanpor® (Epitest, Ltd. Oy). After removal of patch, skin reactions were assessed according to the ICDRG classification for 2 days. Twenty-eight healthy female volunteers, aged 20 and 21, were also tested with the sample as controls. None gave a positive reaction.

No dermal reactions were observed in all treated patients. Thus the test material was not considered to be a potent sensitizer in human patients suffering from pigmented contact dermatitis.

This is supported by the results of a guinea pig maximization assay performed to determine the allergenic potential of the other structurally similar chemical. During the induction phase, guinea pigs were induced intradermally with injections of 0.1 mL of 0.5% aqueous solution of test chemical on 3 times per day on 5 consecutive days. After a rest period of 4 weeks, animals were challenged with the same concentration and then observed for allergic effects. The treated guinea pigs did not reveal any sensitization potential. Hence, the test chemical was considered to be not sensitizing to the skin of treated guinea pigs.

Based on the available data for the structurally similar read across substances and applying the weight of evidence approach, it can be concluded that the target chemical will also tend to behave in a similar that of the read across substances. Therefore,  Reaction mass of 3H-​Indolium, 2-​[[2-​(4-​methoxyphenyl)​-​2-​methylhydrazinyliden​e]​methyl]​-​1,​3,​3-​trimethyl-​ & acetate was estimated to be not sensitizing to skin.

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

Based on the available studies for the structurally similar read across chemicals, weight of evidence approach was applied to assess the dermal sensitization potential of  Reaction mass of 3H-​Indolium, 2-​[[2-​(4-​methoxyphenyl)​-​2-​methylhydrazinyliden​e]​methyl]​-​1,​3,​3-​trimethyl-​ & acetate.

A study was performed in human volunteers to determine the degree of allergic reactions caused by the structurally similar read across chemical.

The test chemical 1% in petrolatum was applied onto the back of 8 healthy patients for 24 hours by using Finn Chambers® on Scanpor® (Epitest, Ltd. Oy). After removal of patch, skin reactions were assessed according to the ICDRG classification for 2 days. Twenty-eight healthy female volunteers, aged 20 and 21, were also tested with the sample as controls. None gave a positive reaction.

No dermal reactions were observed in all treated patients. Thus the test material was not considered to be a potent sensitizer in human patients suffering from pigmented contact dermatitis.

This is supported by the results of a guinea pig maximization assay performed to determine the allergenic potential of the other structurally similar chemical. During the induction phase, guinea pigs were induced intradermally with injections of 0.1 mL of 0.5% aqueous solution of test chemical on 3 times per day on 5 consecutive days. After a rest period of 4 weeks, animals were challenged with the same concentration and then observed for allergic effects. The treated guinea pigs did not reveal any sensitization potential. Hence, the test chemical was considered to be not sensitizing to the skin of treated guinea pigs.

Based on the available data for the structurally similar read across substances and applying the weight of evidence approach, it can be concluded that the target chemical will also tend to behave in a similar that of the read across substances. Therefore,  Reaction mass of 3H-​Indolium, 2-​[[2-​(4-​methoxyphenyl)​-​2-​methylhydrazinyliden​e]​methyl]​-​1,​3,​3-​trimethyl-​ & acetate was estimated to be not sensitizing to skin.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

The results of the experimental studies from the structurally similar read across substances indicate a possibility that  Reaction mass of 3H-​Indolium, 2-​[[2-​(4-​methoxyphenyl)​-​2-​methylhydrazinyliden​e]​methyl]​-​1,​3,​3-​trimethyl-​ & acetate can be not sensitizing to skin.

Hence by applying the weight of evidence approach,  Reaction mass of 3H-​Indolium, 2-​[[2-​(4-​methoxyphenyl)​-​2-​methylhydrazinyliden​e]​methyl]​-​1,​3,​3-​trimethyl-​ & acetate be considered to be not sensitizing to skin.