Dibenzo[b,f]cyclohepten-1-one

Endpoint summary

Description of key information

The skin sensitization potential of 1H-dibenzo[a,d][7]annulen-1-one (2222-33-5 ) was estimated by using OECD QSAR toolbox v3.4 with log kow as the primary descriptor and considering the six closest read across substances. 1H-dibenzo[a,d][7]annulen-1-one (2222-33-5 ) was predicted to be not sensitizing to the skin of Pirbright-White guinea pig.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification

Justification for type of information:

Data is from QSAR toolbox v. 3.4 and the QMRF report has been attached.

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Principles of method if other than guideline:

Prediction was done using OECD QSAR toollbox v3.4

GLP compliance:

not specified

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

Not specified

Specific details on test material used for the study:

- Name of test material (as cited in study report): Dibenzo[b,f]cyclohepten-1-one
- Molecular formula: C15H10O
- Molecular weight: 206.243 g/mol
- Substance type: Organic
- Physical state: Solid

Species:

guinea pig

Strain:

other: Pirbright-White

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
-Strain specifics: Hoe: DHPK (SPFLac)- Source: Hoechst AG, Kastengrund, SPF breeding colony
- Weight at study initiation: mean 385 g (range: 352-431 g)
- Housing: in groups of five animals in Makrolon type 4 cages in fully air-conditioned rooms
- Diet (e.g. ad libitum): standard diet, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: not necessary (breeding at identical conditions)- Randomisation: randomisation scheme 95.0421

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3 °C
- Humidity (%): 50 ± 20%
- Air changes (per hr): fully air-conditioned
- Photoperiod (hrs dark / hrs light):12/12

Route:

intradermal and epicutaneous

Vehicle:

other: Freund's Adjuvant, semi-liquid paraffin and petrolatum

Concentration / amount:

5%

Day(s)/duration:

48 hour

Route:

epicutaneous, occlusive

Vehicle:

other: Freund's Adjuvant, semi-liquid paraffin and petrolatum

Concentration / amount:

5%

Day(s)/duration:

48 Hour

No. of animals per dose:

10 animals

Details on study design:

No data available.

Challenge controls:

No data available.

Positive control substance(s):

not specified

Statistics:

No data available.

Reading:

1st reading

Hours after challenge:

48

Group:

test chemical

Dose level:

5%

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

No skin sensitization reaction observed.

Remarks on result:

no indication of skin sensitisation

The prediction was based on dataset comprised from the following descriptors: "Skin Sensitisation"
Estimation method: Takes mode value from the 5 nearest neighbours
Domain  logical expression:Result: In Domain

(((("a" or "b" or "c" )  and ("d" and ( not "e") )  )  and "f" )  and ("g" and "h" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Cyclo conjugated system AND Cycloketone AND Fused unsaturated carbocycles AND Quinoid compounds by Organic Functional groups

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Fused unsaturated carbocycles AND Overlapping groups AND Quinoid compounds by Organic Functional groups (nested)

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Carbonyl, olefinic attach [-C(=O)-] AND Ketone in a ring, olefinic aromatic attach AND Miscellaneous sulfide (=S) or oxide (=O) AND Olefinic carbon [=CH- or =C<] by Organic functional groups (US EPA)

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Non binder, without OH or NH2 group by Estrogen Receptor Binding

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Non binder, impaired OH or NH2 group OR Non binder, MW>500 by Estrogen Receptor Binding

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "g"

Parametric boundary:The target chemical should have a value of log Kow which is >= 1.38

Domain logical expression index: "h"

Parametric boundary:The target chemical should have a value of log Kow which is <= 3.67

Interpretation of results:

other: not sensitising

Conclusions:

The skin sensitization potential of 1H-dibenzo[a,d][7]annulen-1-one (2222-33-5 ) was estimated by using OECD QSAR toolbox v3.4 with log kow as the primary descriptor and considering the six closest read across substances. 1H-dibenzo[a,d][7]annulen-1-one (2222-33-5 ) was predicted to be not sensitizing to the skin of Pirbright-White guinea pig.

Executive summary:

The skin sensitization potential of 1H-dibenzo[a,d][7]annulen-1-one (2222-33-5 ) was estimated by using OECD QSAR toolbox v3.4 with log kow as the primary descriptor and considering the six closest read across substances. 1H-dibenzo[a,d][7]annulen-1-one (2222-33-5 ) was predicted to be not sensitizing to the skin of Pirbright-White guinea pig.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Skin sensitization

In different studies, 1H-dibenzo[a,d][7]annulen-1-one (2222-33-5 )has been investigated for potential for dermal sensitization to a greater or lesser extent. The prediction is based on in vivo experiments in guinea pig for target chemical 1H-dibenzo[a,d][7]annulen-1-one (2222-33-5 )and its structurally similar read across substances 5, 12-dihydroquino[2,3-b]acridine-7,14-dione (1047-16-1). The predicted data using the OECD QSAR toolbox and Danish QSAR have also been compared with the experimental data of read across.

The skin sensitization potential of 1H-dibenzo[a,d][7]annulen-1-one (2222-33-5 ) was estimated by SSS (2017) using OECD QSAR toolbox v3.4 with log kow as the primary descriptor and considering the six closest read across substances. 1H-dibenzo[a,d][7]annulen-1-one (2222-33-5 ) was predicted to be not sensitizing to the skin of Pirbright-White guinea pig.

Another prediction done using the Danish (Q) SAR Database, the skin sensitization was estimated to be negative on guinea pig and human for1H-dibenzo[a,d][7]annulen-1-one . Using Battery algorithm model of Danish QSAR, Allergic Contact Dermatitis for 1H-dibenzo[a,d][7]annulen-1-one (2222-33-5 ) estimated to be not sensitizing when applied to human and guinea pig skin.

Further supported by experimental data conducted by Environmental Protection Agency, Washington, DC. Office of Toxic ( EPA/OTS; Doc #86-920000391S, NTIS/OTS0533729, 1991) on structurally similar read across substance 5, 12-dihydroquino[2,3-b]acridine-7,14-dione (1047-16-1)in albino guinea pigs. The read across substances share high similarity in structure and log kow . Therefore, it is acceptable to derive information on skin sensitization from the analogue substance. Tests for skin sensitization potential have been conducted for 5, 12-dihydroquino[2,3-b]acridine-7,14-dione (1047-16-1) on albino guinea pigs.When a 10% suspension of the material in water containing 1% of Duponol PT was applied to intact skin of 10 male albino guinea pigs, it produced mild irritation on five animals and none on the others. Applications of the same concentration to abraded skin were slightly more irritating. Challenge tests, following nine exposures of the 10% suspension to abraded skin and 2 weeks rest period, showed no sensitization potential. Therefore 5, 12-dihydroquino[2,3-b]acridine-7,14-dione (1047-16-1) was considered to be non sensitizer in albino guinea pigs.

Thus based on the above predictions on 1H-dibenzo[a,d][7]annulen-1-one (2222-33-5 ) as well as its read across substances and applying weight of evidence, it can be concluded that 1H-dibenzo[a,d][7]annulen-1-one (2222-33-5 ) is not a skin sensitizer. Thus comparing the above annotations with the criteria of CLP regulation, 1H-dibenzo[a,d][7]annulen-1-one (2222-33-5 ) can be considered as not classified for skin sensitization effects.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Thus comparing the above annotations with the criteria of CLP regulation, 1H-dibenzo[a,d][7]annulen-1-one (2222-33-5 ) can be considered as not classified for skin sensitization effects.