Cyanoguanidine

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

other: No info on GLP; no specification of test compound; 5th bacteria strain is TA1538 (according to old guidelines); only TA98 & TA100 were tested with S9 mix. S9 mix from mice, not rats, no indication if induced. This study is listed in OECD SIDS of DCD (3)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1989

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

not specified

Principles of method if other than guideline:

Salmonella typhimurium strains TA98, TA100, TA1535, TA1537, TA1538 were tested with and without metabolic activation. Concentrations without metabolic activation: 0.01, 0.05, 0.1, 0.5, 1.0, 2.5, 5.0 mg/plate;wWith metabolic activation (mouse S-9 mix): 0.1, 0.5, 1.0, 2.5, 5.0 mg/plate, (maize fraction S-14): 0.1, 1.0, 5.0, 10.0 mg/plate

GLP compliance:

no

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Cyanoguanidine

EC Number:

207-312-8

EC Name:

Cyanoguanidine

Cas Number:

461-58-5

Molecular formula:

C2H4N4

IUPAC Name:

1-cyanoguanidine

Test material form:

solid: particulate/powder

Method

Species / strain

Species / strain / cell type:

S. typhimurium, other: TA98, TA100, TA1535, TA1537, TA1538

Additional strain / cell type characteristics:

other: histidine auxotrophy

Metabolic activation:

with and without

Metabolic activation system:

S-9 mix, S-14 mix

Test concentrations with justification for top dose:

Without metabolic activation: 0.01, 0.05, 0.1, 0.5, 1.0, 2.5, 5.0 mg/plate,
With metabolic activation (mouse S-9 mix): 0.1, 0.5, 1.0, 2.5, 5.0 mg/plate,
(maize fraction S-14): 0.1, 1.0, 5.0, 10.0 mg/plate

Results and discussion

Test results

Species / strain:

S. typhimurium, other: TA98, TA100, TA1535, TA1537, TA1538

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Any other information on results incl. tables

This substance reduced the numbers of bacterial colonies in plates with 10, 5 or 2.5 mg/plate, respectively. It did not exert mutagenic effects on tester strains incubated was observed in strain TA1535 when tested with 0.1, 0.5 and 1.0 mg per plate.

Applicant's summary and conclusion

Conclusions:

negative without metabolic activation
negative with metabolic activation S-9 mix
ambiguous with metabolic activation S-14 fraction, only TA98
Cyanoguanidine became not mutagenic in all of the tested strains of Salmonella typhimurium without metabolic activation and with metabolic activation by the S-9 mix.
Cyanoguanidine became mutagenic for Salmonella strain TA98 after metabolic activation by the S-14 plant fraction.
Comment: the mutagenic effect for Salmonella strain TA98 after metabolic activation by the S-14 plant fraction is not relevant in regards with toxic/mutagenic effects in humans because of different enzymes (plant-human).

Executive summary:

The mutagenic activity of Cyanoguanidine was tested in reversion mutagnicity assays with a set of histidine auxotrophic strains of Salmonella typhimurium (TA98, TA100, TA1535, TA1537, TA1538). A possible metabolic activation of the test substance by cell free fractions from maize-seedlings (S-14-fraction) and for comparison from mouse liver (s-9 mix) was examined. Following concentrations were used: Without metabolic activation: 0.01, 0.05, 0.1, 0.5, 1.0, 2.5, 5.0 mg/plate, With metabolic activation (mouse S-9 mix): 0.1, 0.5, 1.0, 2.5, 5.0 mg/plate, (maize fraction S-14): 0.1, 1.0, 5.0, 10.0 mg/plate.

Cyanoguanidine did not exert mutagenic activity in the bacterial strains without metabolic activation. Cyanoguanidine became mutagenic for Salmonella strain TA98 after metabolic activation by the S-14 plant fraction. Cyanoguanidine was not mutagenic in the presence of S-9 mix made from mouse liver.