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Toxicological information

Genetic toxicity: in vitro

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Administrative data

Endpoint:
in vitro gene mutation study in bacteria
Remarks:
Type of genotoxicity: gene mutation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
no data
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The data was retrieved from the NTP website. No study report avialable. No details on test substance composition. Protocol and results are available online. NTP study data is generally well trusted.

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1999

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Principles of method if other than guideline:
The study was performed accoding to standard NTP Protocol which is based on Zeiger (1992).
GLP compliance:
not specified
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Test substance: Sodium chlorate. No further data . For the carcinogenicity study in which this mutagenicity study was summarized the test substance was obtained from Aldrich Chemical Company, Inc. (Milwaukee, WI)

Method

Target gene:
Histidine operon
Species / strain
Species / strain / cell type:
other: Salmonella typhimurium TA97 - TA98 - TA100 - TA102 - TA104 - TA1535
Additional strain / cell type characteristics:
not specified
Metabolic activation:
with and without
Metabolic activation system:
S9-mix from rat or hamster
Test concentrations with justification for top dose:
100, 333, 1000, 3333 and 10000 microgram/plate
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: no data
Controls
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: see "any other information on materials...."
Details on test system and experimental conditions:
METHOD OF APPLICATION: preincubation

DURATION
- Preincubation period: 20 minutes
- Exposure duration: 2 days
- Expression time (cells in growth medium): not applicable
- Selection time (if incubation with a selection agent): not applicable
- Fixation time (start of exposure up to fixation or harvest of cells): not applicable

SELECTION AGENT (mutation assays): histidine
SPINDLE INHIBITOR (cytogenetic assays): not applicable
STAIN (for cytogenetic assays): not applicable

NUMBER OF REPLICATIONS: triplicate

NUMBER OF CELLS EVALUATED: not applicable

DETERMINATION OF CYTOTOXICITY
- Method: In the methos it is stated: All chemicals were run initially in a toxicity assay to determine the appropriate dose range for the mutagenicity
assay. The toxicity assay was performed using TA100 or the system developed by Waleh et al. [1982]. Toxic concentrations were defined as those that produced a decrease in the number of his+ colonies, or a clearing in the density of the background lawn, or both.
No data about a cytotoxicity test has been reported by the NTP.

OTHER EXAMINATIONS:
- Determination of polyploidy: not applicable
- Determination of endoreplication: not applicable
Evaluation criteria:
A chemical was judged mutagenic or weakly mutagenic if it produced a reproducible, dose-related response over the solvent control, under a single metabolic activation condition, in replicate trials. A chemical was judged questionable if the results of individual trials were not reproducible, if increases in his+ revertants did not meet the criteria for a weakly mutagenic response, or if only single doses produced increases in his+ revertants in repeat trials.Chemicals were judged nonmutagenic (-) if they did not meet the criteria for a mutagenic or questionable response.
Statistics:
-

Results and discussion

Test results
Species / strain:
other: Salmonella typhimurium TA97 - TA98 - TA100 - TA102 - TA104 - TA1535
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not specified
Vehicle controls validity:
valid
Untreated negative controls validity:
not examined
Positive controls validity:
valid
Additional information on results:
TEST-SPECIFIC CONFOUNDING FACTORS
- Effects of pH: no data
- Effects of osmolality: no data
- Evaporation from medium: not applicable
- Water solubility: water soluble
- Precipitation: no data
- Other confounding effects: no data

RANGE-FINDING/SCREENING STUDIES: no data

COMPARISON WITH HISTORICAL CONTROL DATA: no data

ADDITIONAL INFORMATION ON CYTOTOXICITY: no data
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
negative

Under the criteria of this study sodium chlorate (100 to 10,000 µg/plate) was not mutagenic in S. typhimurium strains TA97, TA98, TA100, TA102, TA104, or TA1535, with or without induced rat or hamster liver S9 enzymes.
Executive summary:

Testing was performed as reported by Zeiger et al. (1992). Sodium chlorate was sent to the laboratory as a coded aliquot. It was incubated with the Salmonella typhimurium tester strains TA97, TA98, TA100, TA102, TA104, and TA1535 either in buffer or S9 mix (metabolic activation enzymes and cofactors from Aroclor 1254-induced male Sprague-Dawley rat or Syrian hamster liver) for 20 minutes at 37° C. Top agar supplemented with L-histidine and d-biotin was added, and the contents of the tubes were mixed and poured onto the surfaces of minimal glucose agar plates. Histidine-independent mutant colonies arising on these plates were counted following incubation for 2 days at 37° C. Each trial consisted of triplicate plates of concurrent positive and negative controls and at least five doses of sodium chlorate. In the absence of toxicity, 10,000 µg/plate was selected as the high dose.Test concentrations were 100, 333, 1000, 3333 and 10000 microgram/plate. All trials were repeated at the same or a higher S9 fraction. In this assay, a positive response is defined as a reproducible, dose-related increase in histidine-independent (revertant) colonies in any one strain/activation combination. An equivocal response is defined as an increase in revertants that is not dose related, is not reproducible, or is not of sufficient magnitude to support a determination of mutagenicity. A negative response is obtained when no increase in revertant colonies is observed following chemical treatment. There is no minimum percentage or fold increase required for a chemical to be judged positive or weakly positive. In this assay sodium chlorate did not induce an increase in the number of revertant colonies. Sodium chlorate (100 to 10,000 µg/plate) was not mutagenic in S. typhimurium strains TA97, TA98, TA100, TA102, TA104, or TA1535, with or without induced rat or hamster liver S9 enzymes.