N-hydroxyphthalimide

Endpoint summary

Description of key information

The skin sensitization potential of 2-hydroxy-1H-isoindole-1,3(2H)-dione (524-38-9) was estimatedby SSS (2017) using OECD QSAR toolbox v3.4 with log kow as the primary descriptor and considering the six closest read across substances. 2-hydroxy-1H-isoindole-1,3(2H)-dione (524-38-9) was predicted to be non sensitizing to the skin of 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 predicted using OECD QSAR toolbox version 3.4 and the supporting QMRF report has been attached.

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.4.

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:

- IUPAC name: 2-hydroxy-1H-isoindole-1,3(2H)-dione
- Molecular formula: C8H5NO3
- Molecular weight: 163.132 g/mol
- Smiles notation: c12c(C(=O)N(C1=O)O)cccc2
- InChl: 1S/C8H5NO3/c10-7-5-3-1-2-4-6(5)8(11)9(7)12/h1-4,12H
- Substance type: Organic
- Physical state: Solid

Species:

guinea pig

Strain:

not specified

Sex:

not specified

Details on test animals and environmental conditions:

No data available.

Route:

other: No data available.

Route:

other: No data available.

No. of animals per dose:

No data available.

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

Group:

test chemical

No. with + reactions:

0

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: "S M W N"
Estimation method: Takes highest mode value from the 5 nearest neighbours
Domain  logical expression:Result: In Domain

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

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Imides (Acute toxicity) by US-EPA New Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Aryl AND Fused saturated heterocycles AND Hydroxamic acid AND Imide AND N-Hydroxylamine derivatives by Organic Functional groups

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Aryl AND Fused saturated heterocycles AND Hydroxamic acid AND Imide AND Overlapping groups by Organic Functional groups (nested)

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Amide, aromatic attach [-C(=O)N] AND Aromatic Carbon [C] AND Carbonyl, olefinic attach [-C(=O)-] AND Carbonyl, one aromatic attach [-C(=O)-] AND Hydroxy, nitrogen attach [-OH] AND Miscellaneous sulfide (=S) or oxide (=O) AND Nitrogen, two or tree olefinic attach [>N-] AND Olefinic carbon [=CH- or =C<] AND Oxygen, nitrogen attach [-O-] AND Oxygen-subtution at N on [-CO-N-CO-] by Organic functional groups (US EPA)

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Aromatic compound AND Carbonic acid derivative AND Carboxylic acid derivative AND Heterocyclic compound by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as No alert found by Protein binding by OASIS v1.4

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Direct acylation involving a leaving group OR Acylation >> Direct acylation involving a leaving group >> Anhydrides (sulphur analogues of anhydrides)  OR Acylation >> Direct acylation involving a leaving group >> N-Haloacylamides  OR Acylation >> Ester aminolysis or thiolysis OR Acylation >> Ester aminolysis or thiolysis >> Activated aryl esters  OR AN2 OR AN2 >> Michael addition to alpha, beta-unsaturated acids and esters OR AN2 >> Michael addition to alpha, beta-unsaturated acids and esters >> alpha,beta-Unsaturated Carboxylic Acids and Esters OR Michael addition OR Michael addition >> Michael addition on conjugated systems with electron withdrawing group OR Michael addition >> Michael addition on conjugated systems with electron withdrawing group >> alpha,beta-Carbonyl compounds with polarized double bonds  OR Schiff base formation OR Schiff base formation >> Schiff base formation with carbonyl compounds OR Schiff base formation >> Schiff base formation with carbonyl compounds >> Aldehydes OR Schiff base formation >> Schiff base formation with carbonyl compounds >> Aromatic carbonyl compounds OR SN2 OR SN2 >> SN2 Reaction at a sp3 carbon atom OR SN2 >> SN2 Reaction at a sp3 carbon atom >> Activated alkyl esters and thioesters  by Protein binding by OASIS v1.4

Domain logical expression index: "h"

Parametric boundary:The target chemical should have a value of log Kow which is >= -3.42

Domain logical expression index: "i"

Parametric boundary:The target chemical should have a value of log Kow which is <= 2.33

Interpretation of results:

other: Non sensitizer

Conclusions:

The skin sensitization potential of 2-hydroxy-1H-isoindole-1,3(2H)-dione (524-38-9) was estimated by using OECD QSAR toolbox v3.4 with log kow as the primary descriptor and considering the six closest read across substances. 2-hydroxy-1H-isoindole-1,3(2H)-dione (524-38-9) was predicted to be non sensitizing to the skin of guinea pig.

Executive summary:

The skin sensitization potential of 2-hydroxy-1H-isoindole-1,3(2H)-dione (524-38-9) was estimated by  using OECD QSAR toolbox v3.4 with log kow as the primary descriptor and considering the six closest read across substances. 2-hydroxy-1H-isoindole-1,3(2H)-dione (524-38-9) was predicted to be non sensitizing to the skin of guinea pig.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Skin sensitization 

In different studies,2-hydroxy-1H-isoindole-1,3(2H)-dione (524-38-9)has been investigated for potential of skin sensitization to a greater or lesser extent. The studies are based on in vivo experiments in guinea pig and human for target chemical2-hydroxy-1H-isoindole-1,3(2H)-dione (524-38-9) .The predicted data using the OECD QSAR toolbox has also been compared with the experimental data of target chemical.

The skin sensitization potential of 2-hydroxy-1H-isoindole-1,3(2H)-dione (524-38-9) was estimatedby SSS (2017) using OECD QSAR toolbox v3.4 with log kow as the primary descriptor and considering the six closest read across substances. 2-hydroxy-1H-isoindole-1,3(2H)-dione (524-38-9) was predicted to be non sensitizing to the skin of guinea pig.

 It is supported by experimental study conducted by S. FREGERT et al. (CONTACTDERMATITIS; 1983) to evaluate the skin sensitizing potential of target substance 2-hydroxy-1H-isoindole-1,3(2H)-dione (524-38-9) in Human. Patch test was conducted for 2-hydroxy-1H-isoindole-1,3(2H)-dione (524-38-9)on human .A 2-hydroxy-1H-isoindole-1,3(2H)-dione atdilution of (0.00001)10-5 w/w and (0.000001)10-6 (w/w) in ethanol were applied by using patch on to the skin of an old man. He showedpositive reaction at 0.00001 concentration in ethanol but negative at 0.000001 concentration in ethanol during induction exposure. After a rest period of 4 months. At challenge ,test material at thedilution of (0.001)10-3 and (0.0001)10-4(w/w) in ethanol were applied by using patch on to the skin of same person., He showedpositive reaction at(0.001)10-3concentration in ethanol but negative at(0.0001)10-4concentration in ethanol during challenge. Therefore, the substance 2-hydroxy-1H-isoindole-1,3(2H)-dione (524-38-9)wasconsidered to be not sensitizing to human by Patch test.

Thus based on the above predictions on 2-hydroxy-1H-isoindole-1,3(2H)-dione (524-38-9)andapplying weight of evidence, it can be concluded that 2-hydroxy -1H-isoindole-1,3(2H)-di one is not a skin sensitizer. Thus comparing the above annotations with the criteria of CLP regulation, 2-hydroxy-1H-isoindole-1,3(2H)-dione (524-38-9)can be considered as not classified for skin sensitization.

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, 2-hydroxy-1H-isoindole-1,3(2H)-dione (524-38-9)can be considered as not classified for skin sensitization.