3,5-diiodosalicylic acid

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

3,5-diiodosalicylic acid was found to be non-genotoxic.

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:

Prediction is done using QSAR Toolbox version 3.1

GLP compliance:

no

Type of assay:

bacterial reverse mutation assay

Species / strain / cell type:

S. typhimurium TA 1538

Additional strain / cell type characteristics:

not specified

Metabolic activation:

not specified

Metabolic activation system:

S9

Species / strain:

S. typhimurium TA 1538

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 "i" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Phenols (Acute toxicity) by US-EPA New Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.1

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Michael addition OR Michael addition >> Quinone type compounds OR Michael addition >> Quinone type compounds >> Quinoneimine Derivatives OR Michael addition >> Quinone type compounds >> Quinones OR Radical OR Radical >> Generation of reactive oxygen species OR Radical >> Generation of reactive oxygen species >> Coumarins OR Radical >> Generation of reactive oxygen species >> Thiols OR Radical >> Radical mechanism by ROS formation OR Radical >> Radical mechanism by ROS formation >> Nitro Compounds OR Radical >> Radical mechanism by ROS formation >> Quinones OR Radical >> ROS formation after GSH depletion OR Radical >> ROS formation after GSH depletion >> Aromatic and Heterocyclic Primary Amines OR Radical >> ROS formation after GSH depletion >> Quinoneimine Derivatives OR SN1 OR SN1 >> Nitrenium and/or Carbenium ion formation OR SN1 >> Nitrenium and/or Carbenium ion formation >> Urea Derivatives OR SN1 >> Nitrenium ion formation OR SN1 >> Nitrenium ion formation >> Aromatic and Heterocyclic Primary Amines OR SN1 >> Nitrenium ion formation >> Nitro Compounds OR SN1 >> Non-enzymatic nitroso radical and/or nirtosonium cation formation OR SN1 >> Non-enzymatic nitroso radical and/or nirtosonium cation formation >> Urea Derivatives OR SN2 OR SN2 >> P450-mediated epoxidation OR SN2 >> P450-mediated epoxidation >> Coumarins OR SN2 >> SN2 at sp3-carbon atom OR SN2 >> SN2 at sp3-carbon atom >> Sulfonates and Sulfates by DNA binding by OASIS v.1.1

Domain logical expression index: "d"

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

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Michael addition OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> 5-alkoxyindoles OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Alkyl phenols OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Arenes OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Hydroquinones OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Methylenedioxyphenyl OR Michael addition >> Polarised Alkenes-Michael addition OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated ketones OR Michael addition >> Quinones and Quinone-type Chemicals OR Michael addition >> Quinones and Quinone-type Chemicals >> Quinones OR SN1 OR SN1 >> Carbenium Ion Formation OR SN1 >> Carbenium Ion Formation >> Allyl benzenes OR SN1 >> Iminium Ion Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines OR SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >> Aromatic azo OR SN1 >> Nitrenium Ion formation >> Secondary aromatic amine OR SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine OR SN2 OR SN2 >> SN2 at an sp3 Carbon atom OR SN2 >> SN2 at an sp3 Carbon atom >> Aliphatic halides by DNA binding by OECD

Domain logical expression index: "f"

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

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Ester aminolysis OR Acylation >> Ester aminolysis >> Amides OR Acylation >> Ester aminolysis or thiolysis OR Acylation >> Ester aminolysis or thiolysis >> Diarylesters OR Michael addition 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 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 SNAr OR SNAr >> Nucleophilic aromatic substitution on activated halogens OR SNAr >> Nucleophilic aromatic substitution on activated halogens >> Activated haloarenes by Protein binding by OASIS v1.1

Domain logical expression index: "h"

Parametric boundary:The target chemical should have a value of log Kow which is >= 4.18

Domain logical expression index: "i"

Parametric boundary:The target chemical should have a value of log Kow which is <= 4.86

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 1538 with S9 metabolic activation it was estimated that 3,5-diiodosalicylic 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 1538 with S9 metabolic activation it was estimated that 3,5-diiodosalicylic acid does not exhibit positive gene mutation effect.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Additional information

Additional information from genetic toxicity in vitro:

Studies reviewed for Genetic toxicity from QSAR Toolbox 3.1 prediction & QSAR predictions by VegaNIC client version 1.0.6 model.

 

The summary of the results are presented below

 

Sr. No.	Endpoint	Interpretation of results	Strain/SpeciesSources
1	Gene Mutation	Negative with metabolic activation	S. typhimurium TA 1538
2	Gene Mutation	Negative without metabolic activation	S. typhimurium TA 97
3	Chromosome aberration	Negative	Chinese hamster Lung (CHL)
4	Gene Mutation	Negative	S. typhimurium SAi 77
5	Gene Mutation	Negative metabolic activation	Chinese hamster Ovary (CHO)

  

By applying weight of evidence approach, it was concluded that the test substance3,5-diiodosalicylic acid does not exhibit positive gene mutation effect as is the same case for chromosome aberration.

 

Justification for selection of genetic toxicity endpoint
Based on the prediction for in-vitro bacterial reverse mutation assay test on Salmonella typhimurium strain TA 1538 & TA 97 with & without S9 metabolic activation respectively. It was estimated that 3,5-diiodosalicylic acid does not exhibit positive gene mutation effect. Also the chromosome aberration is based on the prediction for in-vitro mammalian chromosome aberration test on Chinese hamster Lung (CHL) with S9 metabolic activation it was estimated that 3,5-diiodosalicylic acid does not exhibit positive chromosomal effect.

Justification for classification or non-classification

3,5-diiodosalicylic acid shows negative activity as is the case for chromosome abberation for the same substance.