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Toxicological information

Genetic toxicity: in vitro

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Administrative data

Endpoint:
in vitro gene mutation study in bacteria
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
secondary literature
Justification for type of information:
Data is from NTRL

Data source

Reference
Reference Type:
secondary source
Title:
MUTAGENICITY EVALUATION OF FDA 75-72 ZINC STEARATE USP(000557-05-1)
Author:
Brusick DJ
Year:
1977
Bibliographic source:
LITTON BIONETICS, INC. '5516 NICHOLSON LANE KENSINGTON, MARYLAND 20795 LBI PROJECT NO. 2672, NATIONAL TECHNICAL INFORMATION SERVICE ,SPRINGFIELD,VA,22161

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: As mention below
Principles of method if other than guideline:
The objective of this study was to evaluate-the test compaund) for genetic activity in microbial assays with and without the addition of mammalian metabolic activation preparations.
GLP compliance:
not specified
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material: Zinc Distearate (ZDS)
- Molecular formula: C18H36O2.1/2Zn
- Molecular weight: 632.3476 g/mol
- Substance type: Organic
- Physical state: Solid (Free flowing white Powder)
- Impurities (identity and concentrations): 0.14 %

Method

Target gene:
Histidine
Species / strain
Species / strain / cell type:
other: TA 1535, TA 1537, TA 1538 ,TA 98 and TA 100
Details on mammalian cell type (if applicable):
Not specified
Additional strain / cell type characteristics:
not specified
Cytokinesis block (if used):
not specified
Metabolic activation:
with and without
Metabolic activation system:
The tissue homogenates and 9,000 x g supernatants were prepared from tissues of the following mammalian species: Mouse - ICR random bred adult males; at - Sprague-Dawley adult males; and monkey - Macaca mulatta adult males
Test concentrations with justification for top dose:
O. 115, 0.0575 and 0.02875%
Vehicle / solvent:
Vehicle
- Vehicle(s)/solvent(s) used: N, N-Dimethyl Formamide
- Justification for choice of solvent/vehicle: Test chemical was soluble in DMF
Controls
Untreated negative controls:
not specified
Negative solvent / vehicle controls:
yes
Remarks:
N, N-Dimethyl Formamide
True negative controls:
not specified
Positive controls:
yes
Positive control substance:
other: -S9;Methylnitrosoguanidine Ethylmethanesulfonate 2-Nitrofluorene Quinacrine mustard +S9; Dimethylnitrosamine 2-Acetylaminofluorene 8-Aminoquinoline 2-Aminoanthracene
Details on test system and experimental conditions:
Details on test system and conditions
METHOD OF APPLICATION;

Experiment I; Plate Tests(overlay method)
Experiment II; Suspension Tests

DURATION
Experiment I;
- Exposure duration:48 to 72 hours

Experiment II;
- Preincubation period: 1 hour
- Exposure duration:48 hours


DETERMINATION OF CYTOTOXICITY
- Method; relative total growth
Evaluation criteria:
Evaluation Criteria for Ames Assay
Because the procedures used to evaluate the mutagenicity of the test chemicalwere semi quantitative. the criteria used to determine positive effects are
inherently subjective and are based primarily on a historical data base. Most data sets are evaluated using the following criteria:
1. Strains TA-1535. TA-1537. and TA-1538
If the solvent control value is within the normal range. a chemical that produces a positive dose response over three concentrations with the lowest increase equal to twice the solvent control value is considered to be mutagenic.
2. Strains TA-98. TA-100. and 04
If the solvent control value is within the normal range. a chemical that produces a positive dose response over three concentrations with the highest increase equal to twice the solvent control value for TA-100 and two to three times the solvent control value for strains TA-98 and 04 is considered to be mutagenic. For these strains. the dose response increase should start at approximately the solvent control value.
3. Pattern
Because TA-1535 and TA-100 were both derived from the same parental strain (G46) and because TA-l~38 and TA-98 were both derived from the same parental strain (03052). There is a built-in redundancy in the microbial assay. In general the two strains of a set respond to the same mutagen and such a pattern is sought. It is also anticipated that if a given strain, e.g. TA1537,responds to a mutagen in nonactivation tests it will generally do so in activation tests. (The converse of this relationship is not expected.) While similar response patterns are not required for all mutagens. they can be used to enhance the reliability of an evaluation decision.
Statistics:
Yes

Results and discussion

Test results
Key result
Species / strain:
other: Salmonella typhimurium TA 1535, TA 1537, TA 1538 ,TA 98 and TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not specified
Vehicle controls validity:
valid
Untreated negative controls validity:
not specified
Positive controls validity:
valid
Remarks on result:
other: No mutagenic effects were observed

Applicant's summary and conclusion

Conclusions:
Zinc Distearate was observed for its mutagenic potential in Salmonella typhimurium TA 1535, TA 1537, TA 1538 ,TA 98 and TA 100 by plate assay and suspension tests in the presence and absence of S9. The test result was considered to be non mutagenic in both the test.
Executive summary:

In genetic toxicity study Zinc Distearate was assessed for its possible mutagenic potential by In vitro bacterial gene mutation assay. The test was performed inSalmonella typhimurium TA 1535, TA 1537, TA 1538 ,TA 98 and TA 100 by plate assay and suspension tests in the presence and absence of S9 . The test substance was exposed at the concentration of O. 115, 0.0575 and 0.02875%.No mutagenic effects were observed in both the assayin the presence and absence of S9.Therefore test substance was considered to be non-mutagenic with and without metabolic activation inSalmonella typhimurium TA 1535, TA 1537, TA 1538 ,TA 98 and TA 100.Hence the substance cannot be classified as gene mutant in vitro.