Indole

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Bacterial in vitro mutagenicity (Ames test) of the target Indole was estimated by using four predictors: Leadscope, ACD/Percepta, Vega and Toxtree decision rule system. The four predictors, which are based on different prediction methodologies (i.e., statistical and expert rule-based), were combined by expert judgment in order to complement each other and thus enhance the reliability of the predictions. In the combined assessment “not reliable” predictions were not considered.  In the case of Indole, ACD/Percepta and Toxtree prediction were not taken into account due to the fact that ACD/Percepta prediction resulted to be undefined, while Toxtree predictions resulted to be not reliable. Leadscope and Vega were in agreement providing negative predictions of different level of confidence (borderline and moderate, respectively). Thus, based on Leadscope and Vega predictions, it was concluded that Indole was predicted as NEGATIVE for bacterial in vitro mutagenicity and the prediction was assessed as moderate reliable.  It is highlighted that both positive and negative experimental Ames test results are available for the target compound Indole. In particular, negative results are reported for Salmonella strains TA97 and TA102, with and without metabolic activation, and TA100, without activation; positive results are reported for Salmonella strains TA98 and TA100, and E. coli WP2uvrA, with and without metabolic activation.

Link to relevant study records

Reference

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

(Q)SAR

Adequacy of study:

key study

Study period:

2017

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 adequate and reliable documentation / justification

Justification for type of information:

QSAR

Principles of method if other than guideline:

QSAR: Bacterial in vitro mutagenicity (Ames test) of the target Indole was estimated by using four predictors: Leadscope, ACD/Percepta, Vega and Toxtree decision rule system. The four predictors, which are based on different prediction methodologies (i.e., statistical and expert rule-based), were combined by expert judgment in order to complement each other and thus enhance the reliability of the predictions. In the combined assessment “not reliable” predictions were not considered.

GLP compliance:

no

Species / strain / cell type:

S. typhimurium TA 97

Species / strain / cell type:

S. typhimurium TA 102

Species / strain / cell type:

S. typhimurium TA 100

Species / strain / cell type:

S. typhimurium TA 98

Species / strain / cell type:

E. coli WP2 uvr A

Key result

Species / strain:

S. typhimurium TA 97

Metabolic activation:

with and without

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

Key result

Species / strain:

S. typhimurium TA 102

Metabolic activation:

with and without

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

Key result

Species / strain:

S. typhimurium TA 100

Metabolic activation:

without

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

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

positive

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

not specified

Untreated negative controls validity:

not specified

Positive controls validity:

not specified

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

positive

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

not specified

Untreated negative controls validity:

not specified

Positive controls validity:

not specified

Species / strain:

E. coli WP2 uvr A

Metabolic activation:

with and without

Genotoxicity:

positive

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:

no mutagenic potential (based on QSAR/QSPR prediction)

Conclusions:

Bacterial in vitro mutagenicity (Ames test) of the target Indole was estimated by using four predictors: Leadscope, ACD/Percepta, Vega and Toxtree decision rule system. The four predictors, which are based on different prediction methodologies (i.e., statistical and expert rule-based), were combined by expert judgment in order to complement each other and thus enhance the reliability of the predictions. In the combined assessment “not reliable” predictions were not considered. In the case of Indole, ACD/Percepta and Toxtree prediction were not taken into account due to the fact that ACD/Percepta prediction resulted to be undefined, while Toxtree predictions resulted to be not reliable. Leadscope and Vega were in agreement providing negative predictions of different level of confidence (borderline and moderate, respectively). Thus, based on Leadscope and Vega predictions, it was concluded that Indole was predicted as NEGATIVE for bacterial in vitro mutagenicity and the prediction was assessed as moderate reliable. It is highlighted that both positive and negative experimental Ames test results are available for the target compound Indole. In particular, negative results are reported for Salmonella strains TA97 and TA102, with and without metabolic activation, and TA100, without activation; positive results are reported for Salmonella strains TA98 and TA100, and E. coli WP2uvrA, with and without metabolic activation

Executive summary:

Bacterial in vitro mutagenicity (Ames test) of the target Indole was estimated by using four predictors: Leadscope, ACD/Percepta, Vega and Toxtree decision rule system. The four predictors, which are based on different prediction methodologies (i.e., statistical and expert rule-based), were combined by expert judgment in order to complement each other and thus enhance the reliability of the predictions. In the combined assessment “not reliable” predictions were not considered.  In the case of Indole, ACD/Percepta and Toxtree prediction were not taken into account due to the fact that ACD/Percepta prediction resulted to be undefined, while Toxtree predictions resulted to be not reliable. Leadscope and Vega were in agreement providing negative predictions of different level of confidence (borderline and moderate, respectively). Thus, based on Leadscope and Vega predictions, it was concluded that Indole was predicted as NEGATIVE for bacterial in vitro mutagenicity and the prediction was assessed as moderate reliable.  It is highlighted that both positive and negative experimental Ames test results are available for the target compound Indole. In particular, negative results are reported for Salmonella strains TA97 and TA102, with and without metabolic activation, and TA100, without activation; positive results are reported for Salmonella strains TA98 and TA100, and E. coli WP2uvrA, with and without metabolic activation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Justification for classification or non-classification

Ames test negative. Need the chromosome aberration test, after it we can classify it.