Registration Dossier

Toxicological information

Genetic toxicity: in vitro

Currently viewing:

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:
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

Reference
Name:
Unnamed
Type:
Constituent
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.