[[4-[[2-(4-cyclohexylphenoxy)ethyl]ethylamino]-2-methylphenyl]methylene]malononitrile

Endpoint summary

Description of key information

Based on the available data for the various test chemicals and applying the weight of evidence approach, it can be concluded that the test chemical will also behave in similar manner. The test chemical was estimated to be not sensitizing to skin. Thus it can be further classified under the category “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:

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:

Weight of evidence approach based on various test chemicals

Justification for type of information:

Weight of evidence approach based on various test chemicals

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

other: Weight of evidence approach based on various test chemicals

Principles of method if other than guideline:

Weight of evidence approach based on various test chemicals

GLP compliance:

not specified

Type of study:

other: Weight of evidence approach based on various test chemicals

Justification for non-LLNA method:

no data available

Species:

other: 1. no data available; 2. guinea pigs; 3. humans

Strain:

not specified

Sex:

male/female

Route:

other: no data available

Vehicle:

not specified

Adequacy of induction:

not specified

Route:

intradermal

Vehicle:

water

Concentration / amount:

6 injections (2 injections of a 0.1 ml Freund’s adjuvant/aqua dest 1:1, 2 injections of 0.1 ml of a 5% test substance formulation, 2 injections of a 0.1 ml 5% test substance formulation in Freund’s adjuvant/aqua dest 1:1)

Adequacy of induction:

not specified

Route:

epicutaneous, occlusive

Vehicle:

olive oil

Concentration / amount:

25% in olive oil

Day(s)/duration:

48 h

Adequacy of induction:

not specified

Route:

epicutaneous, occlusive

Vehicle:

petrolatum

Concentration / amount:

1% in petrolatum

Day(s)/duration:

24 h

Adequacy of induction:

not specified

No.:

#1

Route:

other: no data available

Vehicle:

not specified

Adequacy of challenge:

not specified

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

olive oil

Concentration / amount:

25% in olive oil

Adequacy of challenge:

not specified

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

petrolatum

Concentration / amount:

1% petrolatum

Day(s)/duration:

24 h

Adequacy of challenge:

not specified

No. of animals per dose:

1. no data available
2. 10 female guinea pigs
3. 8 healthy patients

Details on study design:

The data is based on weight of evidence approach based on various test chemicals

Challenge controls:

no data available

Positive control substance(s):

not specified

Reading:

1st reading

Group:

test chemical

No. with + reactions:

0

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 various test chemicals and applying the weight of evidence approach, it can be concluded that the test chemical will also behave in similar manner. The test chemical was estimated to be not sensitizing to skin. Thus it can be further classified under the category “Not Classified” as per CLP regulation.

Executive summary:

The skin sensitization potential of the test chemical was assessed based on the available results from the various test chemicals.

Skin sensitization effects were estimated by four different models i.e, Battery, Leadscope, SciQSAR and CASE Ultra used within Danish QSAR database for the test chemical. Based on estimation, no skin sensitization reactions were observed in guinea pigs and humans. Therefore, the test chemical was considered to be not sensitizing.

This estimated result is supported by OECD 406 Guideline study conducted in 10 female guinea pigs to determine the sensitization potential of the test chemical.

 For intradermal induction, the test animals received 6 injections (2 injections of a 0.1 ml Freund’s adjuvant/aqua dest 1:1, 2 injections of 0.1 ml of a 5% test substance formulation, 2 injections of a 0.1 ml 5% test substance formulation in Freund’s adjuvant/aqua dest 1:1). The intradermal induction with 5% test substance preparations caused moderate and confluent erythema and swelling or intense erythema and swelling in test group animals at 24 h after application. Percutaneous induction was carried out 1 week after intradermal induction. The test substance (25% in olive oil) and the vehicle were applied for 48 h to the animals under occlusive conditions. Incrustation, erythema and oedema were observed in test and control animals at 48 h after beginning of application. After the epicutaneous induction, incrustation, partially open (caused by the intradermal induction) could be observed in addition to moderate and confluent erythema and swelling in all test groups animals. A challenge with a 25% test substance preparation in olive oil was performed 14 days after the epicutaneous induction. No skin reactions could be observed either in control group or in the test group, 24 and 48 hours after removal of the patches. Olive oil, which was applied as a vehicle control to all animals, did not cause any skin reactions. Since no borderline results were observed, a 2nd challenge was not performed.

Therefore, it was concluded that the test substance does not have a sensitizing effect on the skin of the guinea pig in the Maximization Test.

These results are further supported by the Skin sensitization study performed in human patients suffering from pigmented contact dermatitis caused by the commercial dye Brilliant Lake Red R.

The patch of test chemical was applied onto the back of 8 healthy patients for 24 hours by using Finn Chambers® on Scanpor® (Epitest, Ltd. Oy) at a dose of 1% in petrolatum. 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.

 

The negative skin sensitizing effects were observed in all treated patients. Thus the test chemical was considered to be not sensitizing in human patients suffering from pigmented contact dermatitis caused by the commercial Brilliant Lake Red R.

Based on the available data for the various test chemicals and applying the weight of evidence approach, it can be concluded that the test chemical will also behave in similar manner. The test chemical was estimated to be not sensitizing to skin. Thus it can be further classified under the category “Not Classified” as per CLP regulation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

The skin sensitization potential of the test chemical was assessed based on the available results from the various test chemicals.

Skin sensitization effects were estimated by four different models i.e, Battery, Leadscope, SciQSAR and CASE Ultra used within Danish QSAR database for the test chemical. Based on estimation, no skin sensitization reactions were observed in guinea pigs and humans. Therefore, the test chemical was considered to be not sensitizing.

This estimated result is supported by OECD 406 Guideline study conducted in 10 female guinea pigs to determine the sensitization potential of the test chemical.

 For intradermal induction, the test animals received 6 injections (2 injections of a 0.1 ml Freund’s adjuvant/aqua dest 1:1, 2 injections of 0.1 ml of a 5% test substance formulation, 2 injections of a 0.1 ml 5% test substance formulation in Freund’s adjuvant/aqua dest 1:1). The intradermal induction with 5% test substance preparations caused moderate and confluent erythema and swelling or intense erythema and swelling in test group animals at 24 h after application. Percutaneous induction was carried out 1 week after intradermal induction. The test substance (25% in olive oil) and the vehicle were applied for 48 h to the animals under occlusive conditions. Incrustation, erythema and oedema were observed in test and control animals at 48 h after beginning of application. After the epicutaneous induction, incrustation, partially open (caused by the intradermal induction) could be observed in addition to moderate and confluent erythema and swelling in all test groups animals. A challenge with a 25% test substance preparation in olive oil was performed 14 days after the epicutaneous induction. No skin reactions could be observed either in control group or in the test group, 24 and 48 hours after removal of the patches. Olive oil, which was applied as a vehicle control to all animals, did not cause any skin reactions. Since no borderline results were observed, a 2nd challenge was not performed.

Therefore, it was concluded that the test substance does not have a sensitizing effect on the skin of the guinea pig in the Maximization Test.

These results are further supported by the Skin sensitization study performed in human patients suffering from pigmented contact dermatitis caused by the commercial dye Brilliant Lake Red R.

The patch of test chemical was applied onto the back of 8 healthy patients for 24 hours by using Finn Chambers® on Scanpor® (Epitest, Ltd. Oy) at a dose of 1% in petrolatum. 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.

 

The negative skin sensitizing effects were observed in all treated patients. Thus the test chemical was considered to be not sensitizing in human patients suffering from pigmented contact dermatitis caused by the commercial Brilliant Lake Red R.

Based on the available data for the various test chemicals and applying the weight of evidence approach, it can be concluded that the test chemical will also behave in similar manner. The test chemical was estimated to be not sensitizing to skin. Thus it can be further classified under the category “Not Classified” as per CLP regulation.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on the available data for the various test chemicals and applying the weight of evidence approach, it can be concluded that the test chemical will also behave in similar manner. The test chemical was estimated to be not sensitizing to skin. Thus it can be further classified under the category “Not Classified” as per CLP regulation.