4-[(2-chloro-4-nitrophenyl)azo]-N-ethyl-N-[2-[1-(2-methylpropoxy)ethoxy]ethyl]aniline

Endpoint summary

Description of key information

Skin Sensitization:

On the basis of available studies for the structurally similar read across substances, the weight of evidence approach was applied to assess the dermal sensitization ptential for target osubstance.

4-[(2-chloro-4-nitrophenyl)diazenyl]-N-ethyl-N-[2-[1-(2-methylpropoxy)ethoxy]ethyl]aniline  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, other

Remarks:

in vivo

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 read across chemicals

Justification for type of information:

Weight of evidence approach based on structurally similar read across 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 based on structurally similar substances

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 sensitization potential of 4-[(2-chloro-4-nitrophenyl)diazenyl]-N-ethyl-N-[2-[1-(2-methylpropoxy)ethoxy]ethyl]aniline

GLP compliance:

not specified

Type of study:

other: Weight of evidence based on structurally similar read across chemicals

Specific details on test material used for the study:

- Name of test material: 4-((2-Chloro-4-nitrophenyl)azo)-N-ethyl-N-(2-(1-(2-methylpropoxy)ethoxy)ethyl)aniline
- IUPAC name: 4-[(2-chloro-4-nitrophenyl)diazenyl]-N-ethyl-N-[2-[1-(2-methylpropoxy)ethoxy]ethyl]aniline
- Molecular formula: C22H29ClN4O4
- Molecular weight: 448.9481 g/mole
- Smiles : CCN(CCOC(C)OCC(C)C)c1ccc(cc1)/N=N/c2ccc(cc2Cl)[N+](=O)[O-]
- InChl: 1S/C22H29ClN4O4/c1-5-26(12-13-30-17(4)31-15-16(2)3)19-8-6-18(7-9-19)24-25-22-11-10-20(27(28)29)14-21(22)23/h6-11,14,16-17H,5,12-13,15H2,1-4H3/b25-24+
- Substance type: Organic
- Physical state: Solid crystalline powder (white)

Species:

other: guinea pigs and Mice

Strain:

not specified

Sex:

not specified

Details on test animals and environmental conditions:

Weight of evidence based on structurally similar read across chemicals

No. of animals per dose:

The study is based on the weight of evidence approach based on structurally similar read across chemicals

Details on study design:

The study is based on the weight of evidence approach based on structurally similar read across chemicals

Challenge controls:

The study is based on the weight of evidence approach based on structurally similar read across chemicals

Positive control substance(s):

not specified

Vehicle:

dimethylformamide

Concentration:

The study is based on the weight of evidence approach based on structurally similar read across chemicals

No. of animals per dose:

The study is based on the weight of evidence approach based on structurally similar read across chemicals

Details on study design:

The study is based on the weight of evidence approach based on structurally similar read across chemicals

Positive control substance(s):

hexyl cinnamic aldehyde (CAS No 101-86-0)

Statistics:

The study is based on the weight of evidence approach based on structurally similar read across chemicals

Other effects / acceptance of results:

The study is based on the weight of evidence approach based on structurally similar read across chemicals

Reading:

1st reading

Group:

test chemical

Clinical observations:

no dermal reactions observed

Remarks on result:

no indication of skin sensitisation

Parameter:

SI

Test group / Remarks:

test group

Remarks on result:

other: not sensitizing

Cellular proliferation data / Observations:

The study is based on the weight of evidence approach based on structurally similar read across chemicals

Interpretation of results:

other: not sensitizing

Conclusions:

On the basis of available studies for the structurally similar read across substances, the weight of evidence approach was applied to assess the dermal sensitization potential for target substance.
4-[(2-chloro-4-nitrophenyl)diazenyl]-N-ethyl-N-[2-[1-(2-methylpropoxy)ethoxy]ethyl]aniline was estimated to be not sensitizing to skin.

Executive summary:

On the basis of available studies for the structurally similar read across substances, the weight of evidence approach was applied to assess the dermal sensitization potential for target substance.

Kligman – Magnusson procedure was used to determine the dermal sensitization potential of the structurally similar chemical.10 female Hartley guinea pigs were used for the study.

Three pairs of injections (0.05 ml each) were administered intradermally into the shaved interscapular area of each guinea pig: Freund’s complete adjuvant (in equal parts water), 0.1% the test chemical, and a mixture of equal parts of the adjuvant and dye. One week later, the sites were shaved again, and a 48-h occlusive patch containing 25% test chemical in petrolatum was applied. Two weeks later, an occlusive challenge patch containing 25% Disperse Black 9 in propylene glycol was applied to the shaved flank of each guinea pig. Sites were evaluated 24, 48, and 72 hours after patch removal.

No signs of dermal sensitization were observed on female guinea pig skin at any time point after challenge exposure.

Hence, the test chemical was considered to be not sensitizing to guinea pig skin.

This is supported by the study for another structurally similar read across performed on CBA/J female mice according to OECD 429 guideline. The test material was soluble in dimethylformamide (DMF). This vehicle was selected on the basis of the results from a previous solubility study showing that the test chemical was non-soluble in other recommended vehicles, and that 25% (w/v) in DMF was the maximal practicable concentration. The test substance, DMF or HCA was applied in dose concentration 1, 2.5, 5, 10 or 25% (w/v) on the ears (25 μL per ear) of the animals for 3 consecutive days designated as days 1, 2 and 3. After 2 days of resting(day 6), mice received a single intravenous injection of triturated methyl thymidine (3H-TdR). Lymph nodes draining the application sites (auricular nodes) were sampled, pooled per group, and the proliferation of lymphocytes was evaluated by measuring the incorporation of 3H-TdR.The values obtained were used to calculate stimulation indices (SI), and the EC3 was estimated (theoretical concentration resulting in a SI of 3). The irritant potential of HC Yellow n° 7 was assessed by measuring ear thickness on days 1, 2, 3 and 6.

The α hexylcinnamaldehyde at 25% (v/v) in DMF used as positive control. There were no irritation reactions and no lymphoproliferative responses, and the threshold SI of 3 values was not approached in any of the test groups. Hence, the test chemical was considered to be not sensitizing in mice by LLNA method.

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 chemicals. Therefore the target chemical was estimated to be not sensitizing to skin and 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:

On the basis of available studies for the structurally similar read across substances, the weight of evidence approach was applied to assess the dermal sensitization potential for target substance.

Kligman – Magnusson procedure was used to determine the dermal sensitization potential of the structurally similar chemical.10 female Hartley guinea pigs were used for the study.

Three pairs of injections (0.05 ml each) were administered intradermally into the shaved interscapular area of each guinea pig: Freund’s complete adjuvant (in equal parts water), 0.1% the test chemical, and a mixture of equal parts of the adjuvant and dye. One week later, the sites were shaved again, and a 48-h occlusive patch containing 25% test chemical in petrolatum was applied. Two weeks later, an occlusive challenge patch containing 25% Disperse Black 9 in propylene glycol was applied to the shaved flank of each guinea pig. Sites were evaluated 24, 48, and 72 hours after patch removal.

No signs of dermal sensitization were observed on female guinea pig skin at any time point after challenge exposure.

Hence, the test chemical was considered to be not sensitizing to guinea pig skin.

This is supported by the study for another structurally similar read across performed on CBA/J female mice according to OECD 429 guideline. The test material was soluble in dimethylformamide (DMF). This vehicle was selected on the basis of the results from a previous solubility study showing that the test chemical was non-soluble in other recommended vehicles, and that 25% (w/v) in DMF was the maximal practicable concentration. The test substance, DMF or HCA was applied in dose concentration 1, 2.5, 5, 10 or 25% (w/v) on the ears (25 μL per ear) of the animals for 3 consecutive days designated as days 1, 2 and 3. After 2 days of resting(day 6), mice received a single intravenous injection of triturated methyl thymidine (3H-TdR). Lymph nodes draining the application sites (auricular nodes) were sampled, pooled per group, and the proliferation of lymphocytes was evaluated by measuring the incorporation of 3H-TdR.The values obtained were used to calculate stimulation indices (SI), and the EC3 was estimated (theoretical concentration resulting in a SI of 3). The irritant potential of HC Yellow n° 7 was assessed by measuring ear thickness on days 1, 2, 3 and 6.

The α hexylcinnamaldehyde at 25% (v/v) in DMF used as positive control. There were no irritation reactions and no lymphoproliferative responses, and the threshold SI of 3 values was not approached in any of the test groups. Hence, the test chemical was considered to be not sensitizing in mice by LLNA method.

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 chemicals. Therefore the target chemical was estimated to be not sensitizing to skin and 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

The results of the experimental studies from the structurally similar read across substances indicate a possibility that 4-[(2-chloro-4-nitrophenyl)diazenyl]-N-ethyl-N-[2-[1-(2-methylpropoxy)ethoxy]ethyl]aniline can be not sensitizing to skin.

Hence by applying the weight of evidence approach, 4-[(2-chloro-4-nitrophenyl)diazenyl]-N-ethyl-N-[2-[1-(2-methylpropoxy)ethoxy]ethyl]aniline can be considered to be not sensitizing to skin. It can be classified under the category “Not Classified” as per CLP regulation.