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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
Study period:
1.3.1975-25.2.1976
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to Guideline study with acceptable restrictions.

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1976
Report Date:
1976
Reference Type:
publication
Title:
Genetics of somatic mammalian cells. VII. Induction and isolation of nutritional mutants in Chinese hamster cells.
Author:
Kao, F.T. and T.T. Puck
Year:
1968
Bibliographic source:
Proc. Nat. Acad. Sci., 60, 1275 - 1281.
Reference Type:
publication
Title:
Genetics of somatic mammalian cells. IX. Quantitation of mutagenesis by physical and chemical agents.
Author:
Kao, F.T. and T.T. Puck
Year:
1969
Bibliographic source:
J. Cell Physiol., 74(3), 245 - 257.
Reference Type:
publication
Title:
Genetics of somatic mammalian cells. V. Treatment with 5-bromodeoxyuridine and visible light for isolation of nutritionally deficient mutants.
Author:
Puck, T.T. and F.T. Kao
Year:
1967
Bibliographic source:
Proc. Nat. Acad. Sci., 58, 1227- 1234.

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
Deviations:
yes
Remarks:
No metabolic activation, two dose levels, no negative control.
Principles of method if other than guideline:
Wild type cells (Kao and Puck, 1968) capable of growth in both a minimal and enriched medium were exposed. Concentrations were selected from a single cell survival curve obtained according to the method of Puck and Kao (1967). Potential mutants were isolated by the BudR-visible light technique and confirmed by plating the cells in both aforesaid media. A mutant was defined as having growth capability in only the enriched medium. The positive control was ethylmethanesulfonate (Kao and Puck, 1969).
GLP compliance:
no
Remarks:
Unlikely. Study pre-dated even USFDA GPLs.
Type of assay:
mammalian cell gene mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Trinitroglycerin, TNG- Substance type: organic substance- Physical state: capsules, 10% mixture in lactose- Source: SDM No.17, Atlas Chemical Division, ICI America Inc., Wilmigton, DE

Method

Species / strain
Species / strain / cell type:
Chinese hamster Ovary (CHO)
Details on mammalian cell type (if applicable):
- Wild type Chinese hamster ovary cells.
Metabolic activation:
without
Test concentrations with justification for top dose:
50 µg/ml, 144.8 µg/ml.
Controls
Untreated negative controls:
no
Negative solvent / vehicle controls:
no
True negative controls:
no
Positive controls:
yes
Positive control substance:
ethylmethanesulphonate
Evaluation criteria:
Mutagenesis was measured relative to the known mutagen ethyl methanesulfonate.

Results and discussion

Test results
Species / strain:
Chinese hamster Ovary (CHO)
Metabolic activation:
without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not determined
Positive controls validity:
valid

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):negative without metabolic activationNo mutagenic effects were evident from TNG under the conditions of this test.