Difluoroacetic acid

Endpoint summary

Description of key information

Based on the end point values it can be confirmed that the target chemical will be non toxic to animals

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)

Justification for type of information:

QSAR prediction: migrated from IUCLID 5.6

Qualifier:

according to guideline

Guideline:

other: OECD Guideline 401 (Acute Oral Toxicity)

Principles of method if other than guideline:

Data is predicted by QSAR toolbox version 3.1

GLP compliance:

no

Test type:

standard acute method

Species:

rat

Strain:

other: Charles River CD(BR)

Sex:

male

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Doses:

2.6 to 168 mM/kg bw

No. of animals per sex per dose:

5 in 5 dose groups

Control animals:

yes

Sex:

male

Dose descriptor:

LD50

Effect level:

6 957.5 mg/kg bw

Based on:

test mat.

The prediction was based on dataset comprised from the following descriptors: LD50
Estimation method: Takes average value from the 7 nearest neighbours
Domain  logical expression:Result: In Domain

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

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Low (Class I) by Toxic hazard classification by Cramer (original)

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Alkyl halide AND Carboxylic acid by Organic functional groups

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Alkyl halide AND Carboxylic acid AND Overlapping groups by Organic functional groups (nested)

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Alkyl fluoride AND Alkyl halide AND Carbonic acid derivative AND Carboxylic acid AND Carboxylic acid derivative AND Halogen derivative by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "e"

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

Domain logical expression index: "f"

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 >> Anhydrides OR Acylation >> Isocyanates and Related Chemicals OR Acylation >> Isocyanates and Related Chemicals >> Isocyanates OR Michael addition OR Michael addition >> Polarised Alkenes OR Michael addition >> Polarised Alkenes >> Polarised alkene - esters OR Michael addition >> Polarised Alkenes >> Polarised alkene - ketones OR Schiff Base Formers OR Schiff Base Formers >> Direct Acting Schiff Base Formers OR Schiff Base Formers >> Direct Acting Schiff Base Formers >> Di-substituted alpha, beta-unsaturated aldehydes OR Schiff Base Formers >> Direct Acting Schiff Base Formers >> Mono-carbonyls OR SN2 OR SN2 >> SN2 reaction at a sulphur atom OR SN2 >> SN2 reaction at a sulphur atom >> Thiols 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: "g"

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

Domain logical expression index: "h"

Similarity boundary:Target: C(=O)(O)C(F)F
Threshold=20%,
Dice(Atom centered fragments)

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as No alert found by Protein binding by OASIS v1.1

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as SN2 OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> alpha-activated haloalkanes by Protein binding by OASIS v1.1

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Group 14 - Carbon C AND Group 16 - Oxygen O AND Group 17 - Halogens F AND Group 17 - Halogens F,Cl,Br,I,At by Chemical elements

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Group 15 - Nitrogen N OR Group 7 - Trans.Metals Mn,Tc,Re by Chemical elements

Domain logical expression index: "m"

Parametric boundary:The target chemical should have a value of log Kow which is >= -0.783

Domain logical expression index: "n"

Parametric boundary:The target chemical should have a value of log Kow which is <= 0.568

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute oral median lethal dose (LD50) of difluoroacetic acid in Rat (Charles River CD(BR) ) was estimated to be 6957.5mg/kg bw. This value indicates that difluoroacetic acid does not exhibits acute toxicity by the oral route .

Executive summary:

The acute oral median lethal dose (LD50) of difluoroacetic acid in Rat (Charles River CD(BR) ) was estimated to be 6957.5mg/kg bw. This value indicates that difluoroacetic acid does not exhibits acute toxicity by the oral route .

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

6 957.5 mg/kg bw

Quality of whole database:

The data is K2 level as the data has been obtained from QSAR model considered by OECD.

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)

Justification for type of information:

QSAR prediction: migrated from IUCLID 5.6

Qualifier:

according to guideline

Guideline:

other: estimated data

Principles of method if other than guideline:

Data is predicted by QSAR toolbox version 3.1

GLP compliance:

no

Test type:

standard acute method

Species:

rat

Strain:

other: Carworth Farms-Nelson

Sex:

female

Route of administration:

inhalation

Type of inhalation exposure:

whole body

Vehicle:

not specified

Duration of exposure:

8 h

No. of animals per sex per dose:

6

Sex:

female

Dose descriptor:

LC50

Effect level:

28.598 mg/L air

Based on:

test mat.

The prediction was based on dataset comprised from the following descriptors: LC50
Estimation method: Takes average value from the 5 nearest neighbours
Domain  logical expression:Result: In Domain

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

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Low (Class I) by Toxic hazard classification by Cramer (original)

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Alkyl halide AND Carboxylic acid by Organic functional groups

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Alkyl halide AND Carboxylic acid AND Overlapping groups by Organic functional groups (nested)

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Alkyl fluoride AND Alkyl halide AND Carbonic acid derivative AND Carboxylic acid AND Carboxylic acid derivative AND Halogen derivative by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as No alert found by DNA alerts for AMES, MN and CA by OASIS v.1.1

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Schiff base fomers OR Schiff base fomers >> Direct acting Schiff base formers OR Schiff base fomers >> Direct acting Schiff base formers >> Specific Acetate Esters OR SN1 OR SN1 >> Carbenium ion formation OR SN1 >> Carbenium ion formation >> Specific Acetate Esters OR SN2 OR SN2 >> Acylating agents OR SN2 >> Acylating agents >> Specific Acetate Esters OR SN2 >> SN2 at sp3-carbon atom OR SN2 >> SN2 at sp3-carbon atom >> Specific Acetate Esters by DNA alerts for AMES, MN and CA by OASIS v.1.1

Domain logical expression index: "g"

Parametric boundary:The target chemical should have a value of log Kow which is >= -0.633

Domain logical expression index: "h"

Parametric boundary:The target chemical should have a value of log Kow which is <= 0.568

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The LC50 value of difluoroacetic acid in Rat was estimated to be 28.597999573mg/m³ air.Thus considering the CLP Criteria for classification of the substance it is concluded that difluoroacetic acid could not exhibits acute toxicity by the inhalative route.

Executive summary:

The LC50 value of difluoroacetic acid in Rat was estimated to be 28.597999573mg/m³ air.Thus considering the CLP Criteria for classification of the substance it is concluded that difluoroacetic acid does not exhibits acute toxicity by the inhalative route.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

28.598 mg/m³ air

Quality of whole database:

The data is K2 level as the data has been obtained from QSAR model considered by OECD.

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

(Q)SAR

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Justification for type of information:

QSAR prediction: migrated from IUCLID 5.6

Qualifier:

according to guideline

Guideline:

other: OECD Guideline 402 (Acute Dermal Toxicity)

Principles of method if other than guideline:

Data is predicted by QSAR toolbox version 3.1

GLP compliance:

no

Test type:

standard acute method

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Duration of exposure:

presumably 24 hrs

Doses:

not specified

No. of animals per sex per dose:

4

Control animals:

not specified

Sex:

male/female

Dose descriptor:

LD50

Effect level:

5 717.286 mg/kg bw

Based on:

test mat.

Remarks on result:

other: abraded skin

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" or "b" or "c" or "d" )  and "e" )  and "f" )  and "g" )  and ("h" and "i" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Low (Class I) by Toxic hazard classification by Cramer (original)

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Alkyl halide AND Carboxylic acid by Organic functional groups

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Alkyl halide AND Carboxylic acid AND Overlapping groups by Organic functional groups (nested)

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Alkyl fluoride AND Alkyl halide AND Carbonic acid derivative AND Carboxylic acid AND Carboxylic acid derivative AND Halogen derivative by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "e"

Similarity boundary:Target: C(=O)(O)C(F)F
Threshold=10%,
Dice(Atom centered fragments)

Domain logical expression index: "f"

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

Domain logical expression index: "g"

Similarity boundary:Target: C(=O)(O)C(F)F
Threshold=20%,
Dice(Atom centered fragments)

Domain logical expression index: "h"

Parametric boundary:The target chemical should have a value of log Kow which is >= -0.65

Domain logical expression index: "i"

Parametric boundary:The target chemical should have a value of log Kow which is <= 0.0549

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The LD50 value as predicted by the QSAR model was found to be 5717.285 mg/Kg bw of rabbit by the dermal route.

Executive summary:

The LD50 value as predicted by the QSAR model was found to be 5717.285 mg/Kg bw of rabbit by the dermal route. This value suggests that difluoroacetic acid shall not exhibit acute toxicity by the dermal route within this concentration range

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 717.285 mg/kg bw

Quality of whole database:

The data is K2 level as the data has been obtained from QSAR model considered by OECD.

Additional information

ACUTE TOXICITY:

Acute toxicity oral:

Based on studies reviewed for acute toxicity by oral route from reliable sources having Klimish rating 2 considering the weight of evidence approach.

The summary of the results are presented below:

 

Sr. No	Endpoint	Effect values	Species	Sources
1	LD50	6957.5 mg/kg bw	Rat	Predicted data
2	LD50	2285.83 mg/kg bw	Mouse	Predicted data
3	LD50	1737 mg/kg bw	Rat	Data from publication for RA 631-64-1

 

Based on the endpoint values summarized in above table, it was found that LD50 values are between 1737 mg/kg to 6957.5 mg/kg bw. Based upon these available data it can be concluded that the test chemical difluoroacetic acid does not exhibit acute oral toxicity to rat and can be not be classified as acute toxicity as the criteria of CLP regulation.

 

Acute toxicity inhalation:

 

Based on studies reviewed for acute toxicity by inhalation route from reliable sources having Klimish rating 2 considering the weight of evidence approach.

The summary of the results are presented below:

 

Sr. No	Endpoint	Effect values	Species	Sources
1	LC50	28.59 mg/L air	Rat	Predicted data
3	LC50	137 mg/m³ air	Rat	Data from publication for RA 640-19-7

 

Based on the endpoint values summarized in above table, it was found that LC50 values are28.59 mg/L air&137 mg/m³ air. Based upon these available data it can be concluded that the test chemical difluoroacetic acid does not exhibit acute inhalation toxicity to rat and can be not be classified as acute toxicity as the criteria of CLP regulation.

 

Acute toxicity dermal.

 

The LD50 value as predicted using the OECD QSAR toolbox was found to be 5717.285 mg/Kg bw for rabbit by the dermal route. This value suggests that difluoroacetic acid shall not exhibit acute toxicity by the dermal route within this concentration range as the criteria of CLP regulation.

Justification for selection of acute toxicity – oral endpoint

The acute oral median lethal dose (LD50) of difluoroacetic acid in Rat (Charles River CD(BR) ) was estimated to be 6957.5mg/kg bw. This value indicates that difluoroacetic acid does not exhibits acute toxicity by the oral route .

Justification for selection of acute toxicity – inhalation endpoint

The LC50 value of difluoroacetic acid in Rat was estimated to be 28.597999573mg/m³ air.Thus considering the CLP Criteria for classification of the substance it is concluded that difluoroacetic acid does not exhibits acute toxicity by the inhalative route.

Justification for selection of acute toxicity – dermal endpoint

The LD50 value as predicted by the QSAR model was found to be 5717.285 mg/Kg bw of rabbit by the dermal route. This value suggests that difluoroacetic acid shall not exhibit acute toxicity by the dermal route within this concentration range

Justification for classification or non-classification

The substance, difluoroacetic acid, do not have any toxic effects on animals in any of the exposure route i.e. oral, dermal or inhlation and thus based on the C&L regulation it cna be concluded that the substance will not qualify for acute toxicity.