Difluoroacetic acid

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Difluoroacetic acid does not exhibit positive gene mutation effect.

Link to relevant study records

Reference

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

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

Type of assay:

bacterial reverse mutation assay

Species / strain / cell type:

S. typhimurium TA 100

Additional strain / cell type characteristics:

not specified

Metabolic activation:

with

Metabolic activation system:

S9

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

not specified

Untreated negative controls validity:

not specified

Positive controls validity:

not specified

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

The prediction was based on dataset comprised from the following descriptors: "Gene mutation"
Estimation method: Takes highest mode 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 ( not "i") )  )  and ("j" and "k" )  )

Domain logical expression index: "a"

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

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Not possible to classify according to these rules (GSH) by Protein binding potency

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Slightly reactive (GSH) OR Slightly reactive (GSH) >> Substituted haloacetamides (SN2) by Protein binding potency

Domain logical expression index: "d"

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: "e"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Direct acyation involving a leaving group OR Acylation >> Direct acyation involving a leaving group >> Geminal Polyhaloalkanes OR Michael addition OR Michael addition >> alpha, beta-unsaturated carabonyl compounds OR Michael addition >> alpha, beta-unsaturated carabonyl compounds >> Alpha, Beta-Unsaturated Aldehydes OR Radical OR Radical >> Radical mechanism by ROS formation OR Radical >> Radical mechanism by ROS formation >> Geminal Polyhaloalkanes OR Schiff base fomers OR Schiff base fomers >> Direct acting Schiff base formers OR Schiff base fomers >> Direct acting Schiff base formers >> Alpha, Beta-Unsaturated Aldehydes OR Schiff base fomers >> Direct acting Schiff base formers >> Geminal Polyhaloalkanes OR Schiff base fomers >> Multi-step Shiff base formation OR Schiff base fomers >> Multi-step Shiff base formation >> Haloalkanes Containing Electron-Withdrawing Groups OR SN2 OR SN2 >> Epoxidation of Aliphatic Alkenes OR SN2 >> Epoxidation of Aliphatic Alkenes >> Polarized Haloalkene Derivatives OR SN2 >> Internal SN2 reaction with aziridinium and/or cyclic sulfonic ion formation OR SN2 >> Internal SN2 reaction with aziridinium and/or cyclic sulfonic ion formation >> Vicinal Dihaloalkanes OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Geminal Polyhaloalkanes OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Haloalkanes Containing Electron-Withdrawing Groups OR SN2 >> P450-mediated epoxidation OR SN2 >> P450-mediated epoxidation >> Polarized Haloalkene Derivatives OR SN2 >> SN2 at sp3 and activated sp2 carbon atom OR SN2 >> SN2 at sp3 and activated sp2 carbon atom >> Polarized Haloalkene Derivatives 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 Halogens AND Non-Metals by Groups of elements

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Transition Metals by Groups of elements

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Aliphatic halogens by in vitro mutagenicity (Ames test) alerts by ISS

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as alpha,beta-unsaturated carbonyls OR No alert found OR S or N mustard by in vitro mutagenicity (Ames test) alerts by ISS

Domain logical expression index: "j"

Parametric boundary:The target chemical should have a value of log Kow which is >= -1.27

Domain logical expression index: "k"

Parametric boundary:The target chemical should have a value of log Kow which is <= 3.32

Conclusions:

Interpretation of results (migrated information):
negative with metabolic activation

Based on the prediction for in-vitro bacterial reverse mutation assay test on Salmonella typhimurium strain TA 100 with S9 metabolic activation it was estimated that difluoroacetic acid does not exhibit positive gene mutation effect.

Executive summary:

Based on the prediction for in-vitro bacterial reverse mutation assay test on Salmonella typhimurium strain TA 100 with S9 metabolic activation it was estimated that difluoroacetic acid does not exhibit positive gene mutation effect.

In case we consider the functional analog study of tribromoacetic acid, the substance is mutagenic in Salmonella and induced DNA damage (SCGE assay) in CHO cells in the absence of S9. Thus, tribromoacetic acid is slightly mutagenic in bacteria and induced DNA damage in mammalian cells in vitro. Since the functional analog indicates low positive effect and the target chemical prediction is negative, thus it can be infered that the target substance, difluoroacetic acid, will not have genetic toxicity effects.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Additional information

Additional information from genetic toxicity in vitro:

GENETIC TOXICITY:

Based on the prediction for in-vitro bacterial reverse mutation assay test on Salmonella typhimurium strain TA 100 with S9 metabolic activation it was estimated that difluoroacetic acid does not exhibit positive gene mutation effect.

Also based on the publication available for read across for in-vitro bacterial reverse mutation assay test on Salmonella typhimurium strain TA98, TA 100, TA 1535, TA 1537, and TA 1538 with and without S9 metabolic activation shows ambiguous result but another studies shows on Escherichia coli PQ 37 & S. typhimurium TA 100 with and without S9 metabolic activation shows slightly positive gene mutation effect which was dose or concentration dependent effect on the target strain.On which it can be concluded that the difluoroacetic acid does not exhibit positive gene mutation effects. 

Based on studies reviewed for genetic toxicity from reliable sources having Klimish rating 2 considering weight of evidence approach.

 

The summary of the results are presented below

Sr. No.	Endpoint	Interpretation of results	Species	Sources
1.	Genetic toxicity	Negative with & without metabolic activation	S. typhimurium TA 100	Predicted data for target chemical
2.	Genetic toxicity	ambiguous with & without metabolic activation	S. typhimurium TA98, TA 100, TA 1535, TA 1537, and TA 1538	Data from Publication for 79-43-6
3.	Genetic toxicity	slightly positive with & without metabolic activation	Escherichia coli PQ 37	Data from Publication for 79-43-6
4	Genetic toxicity	slightly positive with & without metabolic activation	S. typhimurium TA 100	Data from Publication for 79-43-6
5	Genetic toxicity	slightly positive with & without metabolic activation	Escherichia coli PQ 37	Data from Publication for 631-64-1
6	Genetic toxicity	slightly positive with & without metabolic activation	S. typhimurium TA 100	Data from Publication for 631-64-1
7	Genetic toxicity	Negative	S. typhimurium; unspecified	Data from Publication for 75-96-7
8	Genetic toxicity	Negative	Pleurodeles newt	Data from Publication for 631-64-1
9	Genetic toxicity	Negative	Escherichia coli PQ 37	Data from Publication for 75-96-7

 

Since the functional analogs indicates negative & low positive effect and the target chemical prediction is negative, thus it can be inferred that the target substance, difluoroacetic acid, will not have genetic toxicity effects.

Justification for selection of genetic toxicity endpoint

Based on the prediction for in-vitro bacterial reverse mutation assay test on Salmonella typhimurium strain TA 100 with S9 metabolic activation it was estimated that difluoroacetic acid does not exhibit positive gene mutation effect.

Justification for classification or non-classification

Since the functional analog indicates low positive effect and the target chemical prediction is negative, thus it can be infered that the target substance, difluoroacetic acid, will not have genetic toxicity effects.