N-potassium phthalimide

Endpoint summary

Description of key information

The skin sensitization potential of potassium 1,3-dioxo-1,3-dihydroisoindol-2-ide (1074-82-4) was estimated by SSS (2017) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor and considering the six closest read across substances. 1,3-dioxo-1,3-dihydroisoindol-2-ide (1074-82-4) was predicted to be non sensitizing to the skin of female CBA guinea pig.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (LLNA)

Remarks:

in vivo

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 version 3.3.

Qualifier:

according to guideline

Guideline:

OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)

Principles of method if other than guideline:

Prediction of Skin Sensitisation is done by using QSAR Toolbox 3.3version.

GLP compliance:

not specified

Type of study:

mouse local lymph node assay (LLNA)

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): Phthalimide, potassium salt
- Molecular formula : C8H5NO2.K
- Molecular weight 185.223 g/mol
- Smiles notation : c12c(C(=O)[NH-]C1=O)cccc2.[K+]
- InChl: 1S/C8H5NO2.K/c10-7-5-3-1-2-4-6(5)8(11)9-7;/h1-4H,(H,9,10,11);/q;+1/p-1
- Substance type: Organic
- Physical state: Solid

Species:

mouse

Strain:

CBA

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
20 females, nulliparous and non-pregnant
5 females per group.
Young animals adults were selected (approx. 9 weeks old), with body weight variation within +/- 20% of the sex mean.
Animals had free access to tap water and to pelleted rodent diet.

ENVIRONMENTAL CONDITIONS
15 air changes per hour
temperature of 21.0 +/- 3°C
humidity range : 40-70%
12/12 hours dark/light.

Vehicle:

dimethylformamide

Concentration:

group animal numbers induction (test substance ; % w:w)
1 01-05 0 (DMF)
2 06-10 10
3 11-15 25
4 16-20 50

No. of animals per dose:

Five animals per dose

Details on study design:

Induction : the dorsal surface of both ears was topically treated (25µL/ear) with the test substance concentration, at approx. the same time on each day. The concentrations were stirred with a magnetic stirrer immediately prior to dosing.
The contro animals were treated in the same way as the experimental animals, except that the vehicle was administered instead of the test substance.

Positive control substance(s):

not specified

Statistics:

No data available.

Parameter:

SI

Test group / Remarks:

No skin sensitization effect was observed.

Remarks on result:

other: Not sensitizing

The prediction was based on dataset comprised from the following descriptors: "Skin Sensitisation"
Estimation method: Takes highest mode value from the 7 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 ( not "i") )  )  and ("j" and ( not "k") )  )  and ("l" and ( not "m") )  )  and ("n" and ( not "o") )  )  and ("p" and "q" )  )

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 carbocyclic aromatic AND Fused saturated heterocycles AND Imide by Organic Functional groups

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Aryl AND Fused carbocyclic aromatic AND Fused saturated heterocycles 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 Miscellaneous sulfide (=S) or oxide (=O) AND Nitrogen, two or tree olefinic attach [>N-] AND Olefinic carbon [=CH- or =C<] by Organic functional groups (US EPA)

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Anion AND Aromatic compound AND Carbonic acid derivative AND Carboxylic acid derivative AND Cation 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 DNA binding by OECD

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Michael addition OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Arenes OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Hydroquinones OR SN1 OR SN1 >> Iminium Ion Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines OR SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >> Aromatic azo OR SN1 >> Nitrenium Ion formation >> Aromatic nitro OR SN1 >> Nitrenium Ion formation >> Aromatic phenylureas OR SN1 >> Nitrenium Ion formation >> Primary aromatic amine OR SN1 >> Nitrenium Ion formation >> Unsaturated heterocyclic azo OR SN2 OR SN2 >> SN2 at an sp3 Carbon atom OR SN2 >> SN2 at an sp3 Carbon atom >> Phosphates by DNA binding by OECD

Domain logical expression index: "h"

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

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Non binder, MW>500 OR Non binder, non cyclic structure OR Strong binder, OH group OR Very strong binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Acylation AND Acylation >> Direct Acylation Involving a Leaving group AND Acylation >> Direct Acylation Involving a Leaving group >> Acetates by Protein binding by OECD

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Michael addition OR Michael addition >> Acid imides OR Michael addition >> Acid imides >> Acid imides-MA OR SN2 OR SN2 >> SN2 reaction at a sulphur atom OR SN2 >> SN2 reaction at a sulphur atom >> Disulfides by Protein binding by OECD

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Group 1 - Alkali Earth Li,Na,K,Rb,Cs,Fr AND Group 14 - Carbon C AND Group 15 - Nitrogen N AND Group 16 - Oxygen O by Chemical elements

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Group 16 - Sulfur S by Chemical elements

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Not categorized by Repeated dose (HESS)

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as 3-Methylcholantrene (Hepatotoxicity) Alert by Repeated dose (HESS)

Domain logical expression index: "p"

Parametric boundary:The target chemical should have a value of log Kow which is >= -1.91

Domain logical expression index: "q"

Parametric boundary:The target chemical should have a value of log Kow which is <= 1.3

Interpretation of results:

other: Negative

Conclusions:

Skin sensitization potential of potassium 1,3-dioxo-1,3-dihydroisoindol-2-ide (1074-82-4) was estimated by using OECD QSAR toolbox v3.3 with log kow as the primary descriptor and considering the six closest read across substances. 1,3-dioxo-1,3-dihydroisoindol-2-ide (1074-82-4) was predicted to be non sensitizing to the skin of female CBA guinea pig.

Executive summary:

Skin sensitization potential of potassium 1,3-dioxo-1,3-dihydroisoindol-2-ide (1074-82-4) was estimated by using OECD QSAR toolbox v3.3 with log kow as the primary descriptor and considering the six closest read across substances. 1,3-dioxo-1,3-dihydroisoindol-2-ide (1074-82-4) was predicted to be non sensitizing to the skin of female CBA guinea pig.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Skin sensitization

In different studies, 1,3-dioxo-1,3-dihydroisoindol-2-ide (1074-82-4) has been investigated for potential for dermal sensitization to a greater or lesser extent. The prediction and studies are based on in vivo experiments in guinea pig for target chemical disodium 1,3-dioxo-1,3-dihydroisoindol-2-ide (1074-82-4) and in vitro experimental study on human on its structurally similar read across substances 1H-Isoindole-1,3(2H)-dione, 2-(cyclohexylthio)- (17796-82-6). The predicted data using the OECD QSAR toolbox have also been compared with the experimental data of read across substance.

The skin sensitization potential of potassium 1,3-dioxo-1,3-dihydroisoindol-2-ide (1074-82-4) was estimated by SSS (2017) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor and considering the six closest read across substances. 1,3-dioxo-1,3-dihydroisoindol-2-ide (1074-82-4) was predicted to be non sensitizing to the skin of female CBA guinea pig.

It is supported by experimental data conducted by U.S. Environmental Protection Agency. (HighProduction Volume (HPV) Challenge Program; 2016) on structurally similar read across substance 1H-Isoindole-1,3(2H)-dione, 2-(cyclohexylthio)- (17796-82-6)on Human .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. In vitro Shelanski Repeated Insult Patch Test was performed on human subjects to observe the skin sensitizing effects of 1H-Isoindole-1,3(2H)-dione, 2-(cyclohexylthio)-. Patches 1" square of the rubber stock were applied to the skin of 53 human volunteers and left in place for 24 hours. Readings were taken at the end of 24 hours, and the sites were rested for an additional 24 hours. Patches were reapplied and read again after 24 hours. Fifteen such applications were used. A 10-day rest period followed, and then the challenge application was applied for 24 hours. No positive reactions were observed following the initial application, any subsequent application or after the challenge application. Only mild cumulative irritation was observed in this study. The level used in this study, 2 parts per hundred rubber (2 phr) is about five times higher than what is normally used in compounded rubber stocks. Therefore 1H-Isoindole-1,3(2H)-dione, 2-(cyclohexylthio)- was considered to be non sensitizing in Human by in vitro Shelanski Repeated Insult Patch Test

Thus based on the above predictions on1,3-dioxo-1,3-dihydroisoindol-2-ide (1074-82-4)   as well as its read across substances and applying weight of evidence, it can be concluded that 1,3-dioxo-1,3-dihydroisoindol-2-ide is not a skin sensitizer. Thus comparing the above annotations with the criteria of CLP regulation, 1,3-dioxo-1,3-dihydroisoindol-2-ide (1074-82-4) 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, 1,3-dioxo-1,3-dihydroisoindol-2-ide (1074-82-4) can be considered as not classified for skin sensitization effects.