Benzoic acid, 3-amino-5-[[(2,3-dihydroxypropyl)amino]carbonyl]-2,4,6-triiodo-

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Gene mutation (bacterial reverse mutation assay / Ames test, GLP, OECD TG 471): negative with and without metabolic activation (preincubation and direct plate incorporation method)

 

Link to relevant study records

Reference

Reference 1

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

key study

Study period:

March 1993

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Version / remarks:

1983

Deviations:

yes

Remarks:

no bacteria strain included to detect cross-linking mutagens (e.g. TA 102)

Principles of method if other than guideline:

modified Ames test with preincubation for 60 min at 37°C
No E. coli WP2 or S. typhimurium TA102 strain tested. This requirement was first formulated in the adoption of the guideline in 1997 and thus the study was conducted prior to implementation.

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Target gene:

Histidine gene locus

Species / strain / cell type:

S. typhimurium, other: TA 1535, TA 100, TA 1537, TA 1538 and TA 98

Metabolic activation:

with and without

Metabolic activation system:

S9-mix from Aroclor 1254-induced rat liver

Test concentrations with justification for top dose:

0.10, 0.25, 0.50, 1.00, 2.50 and 5.0 mg/plate

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

Remarks:

DMSO and phosphate buffer pH 7.4, 0.1 mol/l

Positive controls:

yes

Positive control substance:

other: 9-Acridinamine, hydrochloride; 2-Aminoanthracene; 2-Nitrofluorene; Benzo[a]pyrene; Sodium azide; Cyclophosphamide

Details on test system and experimental conditions:

NUMBER OF REPLICATIONS:
- Number of cultures per concentration: triplicate
- Number of independent experiments: one

METHOD OF TREATMENT/ EXPOSURE:
- Test substance added in agar (plate incorporation)

METHODS FOR MEASUREMENT OF CYTOTOXICITY
- Method: background growth inhibition

Evaluation criteria:

The plates were scored for the number of mutant colonies with an automated colony counter (Artek M 982B, Artek Systems Corporation, Farmingdale, NY, USA). The arithmetic means of the number of mutant colonies of the 3 parallel plates in the negative control groups were compared with those of the compound groups. A positive response was considered if at least 5 mg/plate or up to a toxic dose had been tested (or the compound formed precipitates in the agar) and if the number of induced revertants compared to the number of spontaneous ones was reproducibly higher than 2-fold. A dose-dependent increase in the number of revertants was also considered to indicate a mutagenic effect.

Key result

Species / strain:

other: Salmonella typhimurium TA 1535, TA 100, TA 1537, TA 1538, TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Positive controls validity:

valid

Growth inhibition of the background lawn was not observed. There were no precipitates in the agar.

Conclusions:

Interpretation of results: negative

Tamip monoamide is not mutagenic under the conditions of this test system

Executive summary:

Tamip monoamide (ZK 39211) did not show any mutagenic potential in a bacterial reverse mutation assay with S. typhymurium (TA 1535, TA 100, TA 1537, TA 1538, TA 98) when tested with preincubation up to 5.0 mg/plate in the absence and presence of intrinsic metabolic activation (liver mix from Aroclor 1254 -treated rat)

Reference 2

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

key study

Study period:

January 1993

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Version / remarks:

1983

Deviations:

yes

Remarks:

no bacteria strain included to detect cross-linking mutagens (e.g. TA 102)

Principles of method if other than guideline:

Direct plate incorporation procedure was performed. No E. coli WP2 or S. typhimurium TA102 strain tested; no preincubation test performed. These requirements were first formulated in the adoption of the guideline in 1997 and thus the study was conducted prior to implementation of these requirements.

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Target gene:

Histidine gene locus

Species / strain / cell type:

S. typhimurium, other: TA 1535, TA 100, TA 1537, TA 1538 and TA 98

Additional strain / cell type characteristics:

not specified

Metabolic activation:

with and without

Metabolic activation system:

liver mix from Aroclor 1254 -treated rat

Test concentrations with justification for top dose:

0.10, 0.25, 0.50, 1.00, 2.50 and 5 mg/plate

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Positive control substance:

other: 9-Acridinamine, hydrochloride; 2-Aminoanthracene; 2-Nitrofluorene; Benzo[a]pyrene; Sodium azide; Cyclophosphamide

Details on test system and experimental conditions:

NUMBER OF REPLICATIONS:
- Number of cultures per concentration: triplicate
- Number of independent experiments: one

METHOD OF TREATMENT/ EXPOSURE:
- Test substance added in agar (plate incorporation)

METHODS FOR MEASUREMENT OF CYTOTOXICITY
- Method: background growth inhibition

Evaluation criteria:

The plates were scored for the number of mutant colonies with an automated colony counter (Artek M 982B, Artek Systems Corporation, Farmingdale, NY, USA). The arithmetic means of the number of mutant colonies of the 3 parallel plates in the negative control groups were compared with those of the compound groups. A positive response was considered if at least 5 mg/plate or up to a toxic dose had been tested (or the compound formed precipitates in the agar) and if the number of induced revertants compared to the number of spontaneous ones was reproducibly higher than 2-fold. A dose-dependent increase in the number of revertants was also considered to indicate a mutagenic effect.

Key result

Species / strain:

other: Salmonella typhimurium TA 1535, TA 100, TA 1537, TA 1538, TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Positive controls validity:

valid

Growth inhibition of the background lawn was not observed. There were no precipitates in the agar.

Conclusions:

Interpretation of results: negative

Tamip monoamide is not mutagenic under the conditions of this test system

Executive summary:

Tamip monoamide (ZK 39211) did not show any mutagenic potential in a bacterial reverse mutation assay with S. typhymurium (TA 1535, TA 100, TA 1537, TA 1538, TA 98) when tested up to 5.0 mg/plate in the absense and presense of intrinsic metabolic activation (liver mix from Aroclor 1254 -treated rats)

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Tamip monoamide (ZK 39211) did not show any mutagenic potential in a bacterial reverse mutation assay with S. typhymurium (TA 1535, TA 100, TA 1537, TA 1538, TA 98) when tested up to 5.0 mg/plate in the absense and presense of intrinsic metabolic activation (liver mix from Aroclor 1254 -treated rats) (Schering AG, Report No. A483; 1993-06-28)

Tamip monoamide (ZK 39211) did not show any mutagenic potential in a bacterial reverse mutation assay with S. typhymurium (TA 1535, TA 100, TA 1537, TA 1538, TA 98) when tested with preincubation up to 5.0 mg/plate in the absense and presense of intrinsic metabolic activation (liver mix from Aroclor 1254 -treated rat) (Schering AG, Report No. A556; 1993-08-12)

Short description of key information:
Gene mutation (Bacterial reverse muation assay/AMES test, GLP): negative with and without metabolic activation
[Schering AG, Report No. A483; 1993-06-28]

Gene mutation (Bacterial reverse muation assay/AMES test, GLP): negative with and without metabolic activation
[Schering AG, Report No. A556; 1993-08-12]

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

 

Tamip monoamide was tested in two standard genotoxicity tests and did not show any genotoxic potential. 

 

Tamip monoamide is not classified as genotoxic according to the German legislation (TRGS-905).

 

Classification according to Directive 67/548/EEC and Regulation (EC) 1272/2008 (CLP) is not required.