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Toxicological information

Genetic toxicity: in vitro

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Administrative data

Endpoint:
in vitro gene mutation study in mammalian cells
Remarks:
Type of genotoxicity: gene mutation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Adquately documented publication on cyanurate.

Data source

Reference
Reference Type:
publication
Title:
Absence of mutagenic activity for monosodium cyanurate
Author:
Hammond, BG, Barbee, SJ, Wheeler AG and Cascieri, T
Year:
1985
Bibliographic source:
Fundamental and Applied Toxicology 5, pp. 655-664

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
Deviations:
yes
GLP compliance:
not specified
Type of assay:
mammalian cell gene mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
solid: crystalline
Details on test material:
- name in publication: monosodium cyanurate
- supplier: Monsanto company
- composition: 77% cyanurate, 13% sodium and 10% water
- solubility in water: 0.7% w/v
Specific details on test material used for the study:
- name in publication: monosodium cyanurate
- supplier: Monsanto company
- composition: 77% cyanurate, 13% sodium and 10% water
- solubility in water: 0.7% w/v

Method

Species / strain
Species / strain / cell type:
mouse lymphoma L5178Y cells
Metabolic activation:
with and without
Metabolic activation system:
liver S9 preparted from arochlor 1254-induced Sprague-Dawley rats
Test concentrations with justification for top dose:
50 - 2000 μg/plate (toxicity test)
250, 500, 750, 1000, 1250, 1500, 1750 and 2000 μg/plate (mutagenicity test)
Vehicle / solvent:
cell culture medium (F10P) or S-9 mix
Controlsopen allclose all
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
7,12-dimethylbenzanthracene
Remarks:
with S9
Positive control substance:
ethylmethanesulphonate
Remarks:
without S9
Details on test system and experimental conditions:
METHOD OF APPLICATION: in medium; in agar (plate incorporation); preincubation; in suspension; as impregnation on paper disk


DURATION
- Preincubation period: no data
- Exposure duration: 4h
- Expression time (cells in growth medium): 48 h
- Selection time (if incubation with a selection agent): 12 days
- Fixation time (start of exposure up to fixation or harvest of cells):


SELECTION AGENT (mutation assays): trifluorothymidine



NUMBER OF REPLICATIONS: triplicate


NUMBER OF CELLS EVALUATED: Clones growing from 200 cells/plate


DETERMINATION OF CYTOTOXICITY
- Method: cloning efficiency
Evaluation criteria:
Statistic difference to vehicle control
Statistics:
not required

Results and discussion

Test results
Species / strain:
mouse lymphoma L5178Y cells
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
Vehicle controls validity:
valid
Untreated negative controls validity:
not examined
Positive controls validity:
valid

Any other information on results incl. tables

Relative cloning efficiencies ranged from 86 - 111% and 88 - 106% for all incubations with and without metabolic activation, respectively.

Mutant frequency (10exp-6) Mutant frequency (10exp-6)
with S9 without S9
Solvent control 47 42
positive control 538 929
2000 48 58±9
1750 63±17 23±6
1500 39±18 46±9
1250 53±5 41
1000 52±5 40±2
750 48±11 culture lost
500 37±2 36±5
250 58±3 35±5

Applicant's summary and conclusion

Conclusions:
Sodium cyanurate is not mutagenic in mammalian cells in vitro.