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Description of key information

Skin sensitization:

The skin sensitization potential of 2 -furoic was estimated using OECD QSAR toolbox v3.4 with logPow as the primary descriptor.

2 -furoic acid  was estimated to be not skin sensitizing to the skin of   guinea pig. Based on the estimated results, 2 -furoic acid 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:
other: estimated data
Principles of method if other than guideline:
Prediction was done by using OECD QSAR toolbox 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:
IIUPAC:2 furoic acid
CAS NO:88-14-2
EC NO:201-803-0
SMILES:OC(=O)C1=CC=CO1
InChI:1S/C5H4O3/c6-5(7)4-2-1-3-8-4/h1-3H,(H,6,7)
Molecular Formula:C5H4O3
Molecular Weight:112.084
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
Vehicle:
not specified
Concentration:
not specified
No. of animals per dose:
not specified
Details on study design:
not specified
Positive control substance(s):
not specified
Reading:
1st reading
Hours after challenge:
24
Group:
test group
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: not irritating
Conclusions:
2-Furoic acid was considered to be non-skin sensitizing.
Executive summary:

The skin sensitization potential of 2 -Furoic acid was estimated by SSS (2017) using OECD QSAR toolbox v3.4/3.3 with log kow as the primary descriptor.

2 -Furoic acid 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-Furoic acid 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 2-Furoic acid and for its closest read across substances with logKow as the primary descriptor   Benzotriazole (CAS: 95-14-7) and Naphtha (petroleum), catalytic reformed(CAS: 68955-35-1). 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 2-Furoic acid . It was estimated that 2-Furoic acid was non skin sensitizing to skin of guinea pig.

Benzotriazole was evaluated for dermal sensitization in the optimization test. Pirbright white guinea pigs (10/sex/group) were administered 10 consecutive 0.1 ml intracutaneous injections of 0.1% in physiological saline or the vehicle alone. Induction was initiated with an intracutaneous injection both into the shaved flank and into the back, followed by a single injection into the back every other day, Complete Bacto Adjuvant supplemented the 0.1% solution  (1:1, vehicle/adjuvant) in second and third weeks of the induction period. After a 14-day resting period, challenge with 0.1 ml intracutaneous injections of 0.1% in saline into the flanks of control and inducted guinea pigs was given. Injection sites were each inspected 24 hours after induction and challenge. No significant increase in number of positive reactions was noted among inducted guinea pigs. (3/20 positive reactions) relative to controls (2/20 positive reactions). A second challenge, consisting of a subirritant epicutaneous application (30% in vaseline) under occlusive wrap for 24 hours, followed the first by 10 days. Reactions (based on the Draize irritation index) to epicutaneous challenge, evaluated 24 hours later, also failed to demonstrate sensitization in inducted animals (0/20 positive reactions) .No positive reactions were noted.

The above results are further supported by the experimental data summarized in IUCLID Dataset - Naphtha (Petroleum), Catalytic Reformed European Chemicals Bureau (ECB) 2000 for itsclosest read across substances with logKow as the primary descriptor Naphtha (petroleum), catalytic reformed(CAS: 68955-35-1)

Skin sensitization potential was assessed for Naphtha (petroleum), catalytic reformed by Buehler Test method on guinea pigs.

Ten male Hartley guinea pigs were treated once a week for three weeks with 0.4 ml of 50% of the test substance in paraffin oil. Two weeks after the final application they were challenged with 0.4 ml of 25% test substance in paraffin oil. Scores were taken at 24 and 48 hours. A control group was tested using the vehicle only, together witha naive control group and a positive control group.

No dermal reactions were displayed by the test or vehicle control groups; 2/10 animals from the naive control group exhibited slight erythema; 16/20 animals from the positive control group showed slight to moderate erythema, from treatment with 0.4 ml of 0.3% 2,4dinitrochlorobenzene in ethanol in the sensitization phase, followed by 0.4 ml of 0.1% 2,4–dinitrochlorobenzene in acetone in the challenge phase.

No dermal reactions were observed by test or vehicle control group. Naphtha (petroleum), catalytic reformed was considered to be non skin sensitizing.

Based on the available data for the target as well as it read across substances,and applying the weight of evidence approch it can be concluded that 2-Furoic was not skin sensitizing ; and itcan 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,2 -Furoic acidis not likely to cause any skin sensitization reaction.

Hence, 2 -Furoic acid can be evaluated as Not sensitizing to skin and can be classified under the category “Not Classified” as per CLP regulation.