2-furoic acid

Endpoint summary

Description of key information

Acute Oral Toxicity:

The LD50 was estimated to be 2380 mg/kg bw,when six female Crl:WI (Han) rats were orally exposed via gavage with 2-furoic acid (88-14-2).

Acute Inhalation toxicity:

The LC50 value was estimated to be 7.6 mg/l (7600 mg/m³ ) in air,when 5 Crl:CD(SD)IGS BR , Sprague Dawley , SPF male and female rats were exposed with 2-furoic acid (88-14-2) by inhalation for 4 hours.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

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: As mentioned below

Principles of method if other than guideline:

Prediction was done by using OECD QSAR toolbox v3.4,2017

GLP compliance:

not specified

Test type:

other: Estimated data

Limit test:

no

Specific details on test material used for the study:

- Name of test material: 2-furoic acid
- IUPAC name: furan-2-carboxylic acid
- Molecular formula: C5H4O3
- Molecular weight: 112.084 g/mole
- Smiles : c1(C(O)=O)ccco1
- Inchl: 1S/C5H4O3/c6-5(7)4-2-1-3-8-4/h1-3H,(H,6,7)
- Substance type: Organic
- Physical state: Solid powder (Creamish white)

Species:

rat

Strain:

other: Crl:WI (Han)

Sex:

female

Details on test animals and environmental conditions:

No data available

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

No data available

Doses:

2380 mg/kg bw

No. of animals per sex per dose:

Total: 6 females

Control animals:

not specified

Details on study design:

No data available

Statistics:

No data available

Preliminary study:

No data available

Sex:

female

Dose descriptor:

LD50

Effect level:

2 380 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 50% mortality was observed at dose level 2380 mg/kg bw

Mortality:

No mortality was observed at dose level 2380 mg/kg bw

Clinical signs:

No data available

Body weight:

No data available

Gross pathology:

No data available

Other findings:

No data available

The prediction was based on dataset comprised from the following descriptors: LD50
Estimation method: Takes average value from the 5 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" and ( not "l") )  )  and ("m" and ( not "n") )  )  and ("o" and ( not "p") )  )  and ("q" and ( not "r") )  )  and ("s" and ( not "t") )  )  and ("u" and "v" )  )

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 reaction with cycloisomerization OR AN2 >> Nucleophilic addition reaction with cycloisomerization >> Hydrazine Derivatives 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 Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> Polycyclic Aromatic Hydrocarbon and Naphthalenediimide Derivatives OR Non-covalent interaction >> DNA intercalation >> Quinolone Derivatives OR Radical OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Hydrazine Derivatives OR Radical >> ROS formation after GSH depletion OR Radical >> ROS formation after GSH depletion >> Quinone methides OR SN1 OR SN1 >> Alkylation after metabolically formed carbenium ion species OR SN1 >> Alkylation after metabolically formed carbenium ion species >> Polycyclic Aromatic Hydrocarbon and Naphthalenediimide Derivatives OR SN2 OR SN2 >> Alkylation, direct acting epoxides and related OR SN2 >> Alkylation, direct acting epoxides and related >> Epoxides and Aziridines OR SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation OR SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation >> Polycyclic Aromatic Hydrocarbon and Naphthalenediimide Derivatives OR SN2 >> Direct nucleophilic attack on diazonium cation OR SN2 >> Direct nucleophilic attack on diazonium cation >> Hydrazine Derivatives by DNA binding by OASIS v.1.4

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Not possible to classify according to these rules by DPRA Cysteine peptide depletion

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as High reactive OR High reactive >> alpha,beta-carbonyl compounds with polarized multiple bonds OR High reactive >> Di-methacrylic acid esters OR High reactive >> Unsaturated acid anhydrides OR High reactive >> Vinyl pyridines OR Moderate reactive OR Moderate reactive >> Mono-methacrylic acid esters by DPRA Cysteine peptide depletion

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 Schiff Base Formers OR Schiff Base Formers >> Direct Acting Schiff Base Formers OR Schiff Base Formers >> Direct Acting Schiff Base Formers >> Mono-carbonyls by Protein binding by OECD

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Class 3 (unspecific reactivity) by Acute aquatic toxicity classification by Verhaar (Modified) ONLY

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Reactive unspecified by Acute aquatic toxicity MOA by OASIS ONLY

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Very fast by Bioaccumulation - metabolism half-lives ONLY

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Aromatic acid   [-C(=O)-OH] AND Aromatic-H by Biodegradation fragments (BioWIN MITI)

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Aromatic amine   [-NH2  or  -NH-] by Biodegradation fragments (BioWIN MITI)

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Aromatic acid   [-C(=O)-OH] AND Aromatic-H by Biodegradation fragments (BioWIN MITI)

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Aromatic ether  [-O-aromatic carbon] by Biodegradation fragments (BioWIN MITI)

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Aromatic acid   [-C(=O)-OH] AND Aromatic-H by Biodegradation fragments (BioWIN MITI)

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as -CH2-  [cyclic] by Biodegradation fragments (BioWIN MITI)

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Aromatic acid   [-C(=O)-OH] AND Aromatic-H by Biodegradation fragments (BioWIN MITI)

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as -CH2-  [linear] by Biodegradation fragments (BioWIN MITI)

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as Aromatic acid   [-C(=O)-OH] AND Aromatic-H by Biodegradation fragments (BioWIN MITI)

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as Cyanide / Nitriles   [-C#N] by Biodegradation fragments (BioWIN MITI)

Domain logical expression index: "u"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.609

Domain logical expression index: "v"

Parametric boundary:The target chemical should have a value of log Kow which is <= 1.49

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

The LD50 was estimated to be 2380 mg/kg bw, when six female Crl:WI (Han) rats were orally exposed via gavage with 2-furoic acid (88-14-2).

Executive summary:

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute oral toxicity was estimated for 2-furoic acid(88-14-2).The LD50 was estimated to be 2380 mg/kg bw when six female Crl:WI (Han) rats were orally exposed via gavage with 2-furoic acid(88-14-2).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 380 mg/kg bw

Quality of whole database:

Data is Klimicsh 2 and from QSAR Toolbox 3.4 (2017)

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

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: As mentioned below

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.4

GLP compliance:

not specified

Test type:

other: not specified

Limit test:

no

Specific details on test material used for the study:

- Name of test material: 2-furoic acid
- IUPAC name: furan-2-carboxylic acid
- Molecular formula: C5H4O3
- Molecular weight: 112.084 g/mole
- Smiles : c1(C(O)=O)ccco1
- Inchl: 1S/C5H4O3/c6-5(7)4-2-1-3-8-4/h1-3H,(H,6,7)
- Substance type: Organic
- Physical state: Solid powder (Creamish white)

Species:

rat

Strain:

other: Crl:CD(SD)IGS BR , Sprague Dawley , SPF

Sex:

male/female

Details on test animals and environmental conditions:

No data available

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

not specified

Vehicle:

not specified

Details on inhalation exposure:

No data available

Duration of exposure:

4 h

Remarks on duration:

No data available

Concentrations:

7.6 mg/l

No. of animals per sex per dose:

Total : 10 animals
7.6 mg/l = Male : 5 and Females : 5

Control animals:

not specified

Details on study design:

No data available

Statistics:

No data available

Preliminary study:

No data available

Sex:

male/female

Dose descriptor:

LC50

Effect level:

7.6 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: No mortality was observed

Mortality:

No mortality was observed

Clinical signs:

other: No data available

Body weight:

No data available

Gross pathology:

No data available

Other findings:

No data available

The prediction was based on dataset comprised from the following descriptors: LC50
Estimation method: Takes average value from the 7 nearest neighbours
Domain  logical expression:Result: In Domain

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

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 Protein binding by OASIS v1.4

Domain logical expression index: "c"

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 AN2 OR AN2 >> Michael addition to activated double bonds OR AN2 >> Michael addition to activated double bonds >> alpha,beta-Unsaturated Carbonyls and Related Compounds 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 AN2 >> Michael-type addition to quinoid structures  OR AN2 >> Michael-type addition to quinoid structures  >> N-Substituted Aromatic Amines OR Michael addition OR Michael addition >> Michael addition on alpha,beta-Unsaturated carbonyl compounds OR Michael addition >> Michael addition on alpha,beta-Unsaturated carbonyl compounds >> alpha,beta-Aldehydes  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 Michael addition >> Michael addition on conjugated systems with electron withdrawing group >> Conjugated systems with electron withdrawing groups  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 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: "d"

Referential boundary: The target chemical should be classified as High (Class III) by Toxic hazard classification by Cramer (extension) ONLY

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as No alert found by rtER Expert System ver.1 - USEPA

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Multi Cyclic Hydrocarbons by rtER Expert System ver.1 - USEPA

Domain logical expression index: "g"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.518

Domain logical expression index: "h"

Parametric boundary:The target chemical should have a value of log Kow which is <= 2.54

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

The LC50 value for Acute inhalation toxicity study was estimated to be 7.6 mg/l in air,when 5 Crl:CD(SD)IGS BR , Sprague Dawley , SPF male and female rats were exposed with 2-furoic acid (88-14-2) by inhalation for 4 hours.

Executive summary:

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute inhalation toxicity was estimated for 2-furoic acid. The LC50 was estimated to be 7.6 mg/L in air,when 5 Crl:CD(SD)IGS BR , Sprague Dawley , SPF male and female were exposed with 2-furoic acid (88-14-2) by inahaltion for 4 hours.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

7 600 mg/m³

Quality of whole database:

Data is Klimicsh 2 and from QSAR Toolbox 3.4 (2017)

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Acute Oral Toxicity:

In different studies, 2-furoic acid (88-14-2) has been investigated for acute oral toxicity to a greater or lesser extent. Often are the studies based on in vivo experiments and estimated data in rodents, i.e. most commonly in rats 2-furoic acid (88-14-2).The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies.

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute oral toxicity was estimated for 2-furoic acid (88-14-2).The LD50 was estimated to be 2380 mg/kg bw, when six female Crl:WI (Han) rats were orally exposed via gavage with 2-furoic acid (88-14-2).

In another experimental study conducted by E. W. Schafer, Jr. and W. A. Bowles, Jr. (Arch. Environ. Contain. Toxicol. 14, 111-129 (1985)) for the substance 2-furoic acid (88-14-2). Acute oral toxicity study was done in 2 to 4 deer mice using test material 2-furoic acid (88-14-2) .No Mortality was observed at dose 1225 mg/kg/day.Hence,LD50 value was considered to be >1225 mg/kg/day when deer mice were treated with 2-furoic acid (88-14-2) orally via gavage

over the 3-day test period without killing more than 50% of the test animals.

Also these results are further supported by the experimental study conducted by EUROPEAN COMMISSION – European Chemicals Bureau (IUCLID DATASET, EUROPEAN COMMISSION – European Chemicals Bureau, 18–FEB–2000) for the structurally similar read across substance Methyl benzoylformate (CAS no. 15206-55-0). Acute oral toxicity study was done in 15 rats using test material with Methyl benzoylformate (CAS no. 15206-55-0)orally. No Mortality was observed at dose 5000 mg/kg bw.Hence,LD50 value was considered to be >5000 mg/kg body weight,when rats were treated with Methyl benzoylformate (CAS no. 15206-55-0)orally.

Thus, based on the above studies and predictions on 2-furoic acid (88-14-2) and its read across substances, it can be concluded that LD50 value was 2380 mg/kg bw. Thus, comparing this value with the criteria of CLPregulation,2-furoic acid (88-14-2) can be “Not classified” for acute oral toxicity.

 

Acute Inhalation Toxicity:

In different studies, 2-furoic acid (88-14-2) has been investigated for acute inhalation toxicity to a greater or lesser extent. Often are the studies based on in vivo experiments and estimated data in rodents, i.e. most commonly in rats 2-furoic acid (88-14-2).The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies.

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute inhalation toxicity was estimated for 2-furoic acid (88-14-2). The LC50 value was estimated to be 7600 mg/m³ in air,when 5 Crl:CD(SD)IGS BR , Sprague Dawley , SPF male and female rats were exposed with 2-furoic acid (88-14-2) by inhalation for 4 hours.

Also these results are further supported by the experimental study conducted EUROPEAN COMMISSION – European Chemicals Bureau (IUCLID DATASET, EUROPEAN COMMISSION – European Chemicals Bureau, 18–FEB–2000) for the structurally similar read across substance Methyl benzoylformate (CAS no. 15206-55-0). In acute inhalation toxicity study, 5 Rats were exposed to Methyl benzoylformate in the concentration of 10600 mg/m3 inhaled as a Single dose for 4 hour.No mortality was observed at concentration 10600 mg/m³ in air. Therefore, LC50 value was considered to be >10600 mg/ m3 when rats were exposed with Methyl benzoylformate by inhalation for 4 hour.

Thus, based on the above studies and predictions on 2-furoic acid (88-14-2) and its read across substances, it can be concluded that LD50 value was 7600 mg/m³ in air. Thus, comparing this value with the criteria of CLP regulation,2-furoic acid (88-14-2) can be “Not classified” for acute inhalation toxicity.

 

Justification for classification or non-classification

Thus, comparing this value with the criteria of CLP regulation,2-furoic acid (88-14-2) can be “Not classified” for acute oral toxicity and acute inhalation toxicity.