2-furoic acid

Endpoint summary

Description of key information

Skin sensitization:

The skin sensitization potential of test chemical was estimated using OECD QSAR toolbox v3.4 with logPow as the primary descriptor.

Test chemical  was estimated to be not skin sensitizing to the skin of  guinea pig. Based on the estimated results, test chemical can be considered not skin sensitizing and can be classified under the category “Not Classified”as per CLP regulation.

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 QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: estimated data

Principles of method if other than guideline:

Prediction was done by using OECD QSAR toolbox v3.4

GLP compliance:

not specified

Justification for non-LLNA method:

not specified

Species:

guinea pig

Strain:

not specified

Sex:

not specified

Details on test animals and environmental conditions:

No data available

Route:

intradermal and epicutaneous

Vehicle:

not specified

Concentration / amount:

not specified

Day(s)/duration:

6 days

Adequacy of induction:

not specified

No.:

#1

Route:

epicutaneous, open

Vehicle:

not specified

Concentration / amount:

Not specified

Day(s)/duration:

2 weeks

Adequacy of challenge:

not specified

Details on study design:

Not specified

Challenge controls:

not specified

Positive control substance(s):

not specified

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

not specified

Clinical observations:

No skin reactions 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 highest mode value from the 6 nearest neighbours
Domain  logical expression:Result: In Domain

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

Domain logical expression index: "a"

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

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.4

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >>  Michael-type addition, quinoid structures OR AN2 >>  Michael-type addition, quinoid structures >> Quinone methides OR AN2 >> Michael-type conjugate addition to activated alkene derivatives OR AN2 >> Michael-type conjugate addition to activated alkene derivatives >> Alpha-Beta Conjugated Alkene Derivatives with Geminal Electron-Withdrawing Groups OR AN2 >> Nucleophilic addition to alpha, beta-unsaturated carbonyl compounds OR AN2 >> Nucleophilic addition to alpha, beta-unsaturated carbonyl compounds >> Alpha, Beta-Unsaturated Aldehydes OR AN2 >> Schiff base formation OR AN2 >> Schiff base formation >> Alpha, Beta-Unsaturated Aldehydes OR Radical OR Radical >> ROS formation after GSH depletion OR Radical >> ROS formation after GSH depletion >> Quinone methides by DNA binding by OASIS v.1.4

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 OR Non binder, non cyclic structure by Estrogen Receptor Binding

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as No alert found by Protein binding by OECD

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 >> Acetates OR Acylation >> Direct Acylation Involving a Leaving group >> Azlactone OR Michael addition OR Michael addition >> Acid imides OR Michael addition >> Acid imides >> Acid imides-MA OR Michael addition >> Polarised Alkenes OR Michael addition >> Polarised Alkenes >> Polarised alkene - amides OR Michael addition >> Polarised Alkenes >> Polarised alkene - esters OR Michael addition >> Polarised Alkenes >> Polarised alkene - pyridines OR SN2 OR SN2 >> SN2 reaction at sp3 carbon atom OR SN2 >> SN2 reaction at sp3 carbon atom >> Allyl acetates and related chemicals by Protein binding by OECD

Domain logical expression index: "h"

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

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Aryl AND Carboxylic acid AND Furane by Organic Functional groups ONLY

Domain logical expression index: "j"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.69

Domain logical expression index: "k"

Parametric boundary:The target chemical should have a value of log Kow which is <= 1.17

Interpretation of results:

other: non sensitizing

Conclusions:

Test chemical was considered to be non-skin sensitizing.

Executive summary:

The skin sensitization potential of test chemical was estimated by SSS (2017) using OECD QSAR toolbox v3.4/3.3 with log kow as the primary descriptor.

Test chemical 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, test chemical has been investigated for potential for dermal sensitization to a greater or lesser extent. The studies are based on in vivo experiments in guinea pigs along with human data for target chemical and for its closest read across substances with logKow as the primary descriptor. The predicted data using the OECD QSAR toolbox has also been compared with the experimental data.

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the skin sensitization potential was estimated for test chemical. It was estimated that test chemical was non skin sensitizing to skin of guinea pig.

The guinea pig maximization test was conducted on Hartley guinea pigs to determine the skin sensitization potential of test chemical.Intradermal induction was also conducted using 5% of the chemical in propylene glycol while the topical induction was carried out at 0.2ml of undiluted test substance for 48hours under occlusive condition on 10 female and 10 male guinea pigs.Topical induction under occlusion for 48 helicited very slight erythema in 13/20 animals and very slight oedema in 8/20 animals. Only slight skin reactions were observed in 2/20animals after challenge.Since the test chemical did not induce contact sensitization in treated guinea pigs at challenge phase, it was considered to benot sensitizing on skin of guinea pigs.

Test chemicalwas considered to be non sensitizing to guinea pig skin by Draize test.

Test chemical was reported to be a non-sensitizer in Hartley strain albino guinea pigs exposed in a modified Draize procedure to 0.25% in the injection challenge and 20% in the application challenge; vehicles were not reported. Induction consisted of 10 animals given 0.1 ml intradermal injection at four different sites. Following a 2 week rest period, animals were challenged intradermally in one flank and topically in the opposite flank. Reactions were scored 24 h thereafter.There are no reports on the sensitization potential of the remaining perfume ingredients which caused sensitization in our guinea pig test. This suggests that they do not present a problem in use even though they appear to have some sensitization potential when stringently tested in guinea pig test.

The survey of sensitization in man by perfume ingredients which did not cause sensitization in guinea pig tests shows that nearly all the reports, based on patch tests, concern isolated cases. Patch test results show whether a person has or has not become sensitized to the test substance(s); they are an indication, not a proof, that the test substance is responsible for any clinical dermatitis. The evidence available indicates that perfume ingredients that are harmless to the very great majority of persons, do not sensitize guinea pigs by test procedures.

Based on the available data for the target as well as it read across substances, it can be concluded that  test chemical was not skin sensitizing ; and it can be 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

On the basis of available information,test chemical is not likely to cause any skin sensitization reaction.

Hence, test chemical can be evaluated as Not sensitizing to skin and can be classified under the category “Not Classified” as per CLP regulation.