Glycerol trinitrate

Genetic toxicity: in vitro

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

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1976

Report date:

1976

Reference 2

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 3

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 4

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

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

Test material information

Constituent 1

Reference substance name:

Glycerol trinitrate

EC Number:

200-240-8

EC Name:

Glycerol trinitrate

Cas Number:

55-63-0

Molecular formula:

C3H5N3O9 C3H5(NO3)3

IUPAC Name:

propane-1,2,3-triyl trinitrate

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

Key result

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.