Methanone, 1,1'-(1,4-phenylene)bis[1-(4-phenoxyphenyl)-

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, 1,4-phenylene bis[(4-phenoxyphenyl)-methanone] was estimated to be not sensitizing to skin.Comparing the above annotations with the criteria of CLP regulation,1,4-phenylene bis[(4-phenoxyphenyl)-methanone] 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:

other: weight of evidence approach based on similar chemicals

Justification for type of information:

Weight of evidence approach based on 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 based on 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 sensitization potential of 1,4-phenylene bis[(4-phenoxyphenyl)-methanone].

GLP compliance:

not specified

Type of study:

other: Weight of evidence approach

Specific details on test material used for the study:

- Name of test material (IUPAC name): 1,4-phenylene bis[(4-phenoxyphenyl)-methanone]
- Molecular formula: C32H22O4
- Molecular weight: 470.5218 g/mol
- Smiles : c1ccc(cc1)Oc2ccc(cc2)C(=O)c3ccc(cc3)C(=O)c4ccc(cc4)Oc5ccccc5
- InChI : 1S/C32H22O4/c33-31(25-15-19-29(20-16-25)35-27-7-3-1-4-8-27)23-11-13-24(14-12-23)32(34)26-17-21-30(22-18-26)36-28-9-5-2-6-10-28/h1-22H
- Substance Type: Organic
- Physical State: Solid

Species:

other: humans, guinea pigs

Strain:

not specified

Sex:

male/female

Route:

intradermal and epicutaneous

Vehicle:

other: petrolatum, corn oil

Concentration / amount:

Intradermal - 0.05 mL intradermal injection of 5% test chemical in corn oil or 50% test chemical in aqueous Freund's Adjuvant
Epicutaneous - 0.1 mL of 2.5% test chemical

Day(s)/duration:

24 hours

Adequacy of induction:

not specified

Route:

epicutaneous, occlusive

Vehicle:

water

Concentration / amount:

5% in water

Day(s)/duration:

10 application

Adequacy of induction:

not specified

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

petrolatum

Concentration / amount:

0.1 mL of 2.5% test chemical in petrolatum

Day(s)/duration:

24 hours

Adequacy of challenge:

not specified

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

water

Concentration / amount:

5% in water

Day(s)/duration:

24 hours

Adequacy of challenge:

not specified

No. of animals per dose:

1. 10 female guinea pigs
2. 50 human subjects

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

No. with + reactions:

0

Clinical observations:

no signs of sensitization 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, 1,4-phenylene bis[(4-phenoxyphenyl)-methanone] was estimated to be not sensitizing to skin.Comparing the above annotations with the criteria of CLP regulation,1,4-phenylene bis[(4-phenoxyphenyl)-methanone] can be classified under the category “Not Classified”.

Executive summary:

Based on the available studies for the structurally similar read across chemicals, weight of evidence approach was applied to determine the extent of dermal sensitization caused by 1,4-phenylene bis[(4-phenoxyphenyl)-methanone] in living organisms.

Kligman Maximization was performed to determine the dermal sensitization potential of the similar test chemical.

A 0.05 mL intradermal injection of 5% test chemical in corn oil or 50% test chemical in aqueous Freund's Adjuvant was administered to the shaved back of each of ten female albino guinea pigs per solution. Seven days following injection, a topical booster patch containing 10% test chemical in petrolatum was applied for 48 hours. After a rest period of 14 days, a challenge test of 0.1 mL of 2.5% test chemical in petrolatum was applied under an occlusive patch to a virgin site for 24 hours. Sites were scored 24 and 48 hours after patch removal.

No known evidence of skin sensitization was observed in treated guinea pigs after challenge exposure.

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

This is supported by the results of a human repeated insult patch test conducted on 50 subjects to assess the contact sensitization caused by the similar test chemical under occlusive condition.

Induction was carried out at a dose of 5% in water on Mondays, Wednesdays and Fridays, total 10 applications were made. After 24 hours patches were removed and skin sits were scored for primary irritation.   After a rest period of 10-14 days, a challenge patch was applied (to the same site, an adjacent site or both). After 24 hours the patches were removed and the sites were examined for reactions immediately and 24 and 48 hours later.   Since there was no evidence of any contact sensitization, the chemical was considered to be not sensitizing on skin of human subjects.

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, 1,4-phenylene bis[(4-phenoxyphenyl)-methanone] was estimated to be not sensitizing to skin.Comparing the above annotations with the criteria of CLP regulation,1,4-phenylene bis[(4-phenoxyphenyl)-methanone] can be classified under the category “Not Classified”.

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 determine the extent of dermal sensitization caused by 1,4-phenylene bis[(4-phenoxyphenyl)-methanone] in living organisms.

Kligman Maximization was performed to determine the dermal sensitization potential of the similar test chemical.

A 0.05 mL intradermal injection of 5% test chemical in corn oil or 50% test chemical in aqueous Freund's Adjuvant was administered to the shaved back of each of ten female albino guinea pigs per solution. Seven days following injection, a topical booster patch containing 10% test chemical in petrolatum was applied for 48 hours. After a rest period of 14 days, a challenge test of 0.1 mL of 2.5% test chemical in petrolatum was applied under an occlusive patch to a virgin site for 24 hours. Sites were scored 24 and 48 hours after patch removal.

No known evidence of skin sensitization was observed in treated guinea pigs after challenge exposure.

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

This is supported by the results of a human repeated insult patch test conducted on 50 subjects to assess the contact sensitization caused by the similar test chemical under occlusive condition.

Induction was carried out at a dose of 5% in water on Mondays, Wednesdays and Fridays, total 10 applications were made. After 24 hours patches were removed and skin sits were scored for primary irritation.   After a rest period of 10-14 days, a challenge patch was applied (to the same site, an adjacent site or both). After 24 hours the patches were removed and the sites were examined for reactions immediately and 24 and 48 hours later.   Since there was no evidence of any contact sensitization, the chemical was considered to be not sensitizing on skin of human subjects.

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, 1,4-phenylene bis[(4-phenoxyphenyl)-methanone] was estimated to be not sensitizing to skin.Comparing the above annotations with the criteria of CLP regulation,1,4-phenylene bis[(4-phenoxyphenyl)-methanone] can be classified under the category “Not Classified”.

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 1,4-phenylene bis[(4-phenoxyphenyl)-methanone] can be not sensitizing to skin.

Hence by applying the weight of evidence approach, 1,4-phenylene bis[(4-phenoxyphenyl)-methanone] can be considered to be not sensitizing to skin. It can be classified under the category “Not Classified” as per CLP regulation.