Reaction mass of 3H-Indolium, 2-[[2-(4-methoxyphenyl)-2-methylhydrazinylidene]methyl]-1,3,3-trimethyl- and acetate

Endpoint summary

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 for cross-reference:

read-across: supporting information

Reason / purpose for cross-reference:

read-across: supporting information

Qualifier:

according to guideline

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 chemical

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.