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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:
1 (reliable without restriction)

Data source

Reference
Reference Type:
publication
Title:
Mutagenicity of glyceryl trinitrate (nitroglycerin) in Salmonella typhimurium
Author:
Maragos, C.M., Andrews, A.W., Keefer, L.K. and Elespuru, R.K.
Year:
1993
Bibliographic source:
Mutation Research, 298:187-195

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
GLP compliance:
not specified
Type of assay:
bacterial reverse mutation assay

Test material

Constituent 1
Chemical structure
Reference substance name:
Glycerol trinitrate
EC Number:
200-240-8
EC Name:
Glycerol trinitrate
Cas Number:
55-63-0
Molecular formula:
C3H5N3O9
IUPAC Name:
propane-1,2,3-triyl trinitrate

Method

Species / strainopen allclose all
Species / strain / cell type:
S. typhimurium TA 1535
Species / strain / cell type:
S. typhimurium, other:
Details on mammalian cell type (if applicable):
TA1975, TA102, TA1538, TA100, TA100NR, YG1026
Metabolic activation:
with and without
Metabolic activation system:
hamster liver S9
Test concentrations with justification for top dose:
0.1 to 10.0 µmol/plate, 10.1% NG in vehicle
Vehicle / solvent:
lactose
Controls
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
Positive controls:
yes

Results and discussion

Test results
Species / strain:
S. typhimurium TA 1535
Metabolic activation:
with and without
Genotoxicity:
other: positive, but attributed to nitric oxide generation
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
all tested strains
Additional information on results:
One strain (TA1535) of S. typhimurium showed susceptibility to single base pair changes (i.e., C→T transitions) (Wink et al.,1991). A follow-up AMES test on this strain and six others (Maragos et al., 1993) suggested that NG is weakly mutagenic to this particular strain and none of the others tested. Specifically, the single base pair changes were observed in the first or second position of the hisG46 codon (CCC). Using the TA1535 strain, this same pattern of mutagenicity was observed in response to nitric oxide. Given that nitric oxide is generated when NG is metabolized, the authors postulated that it is likely nitric oxide and not NG that is responsible for the mutagenicity observed in the TA1535 strain.

Applicant's summary and conclusion

Conclusions:
negative

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