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Lack of mutagenicity of diphenylhydantoin in in vitro short-term tests
Mutation Research
|August 1, 1984
Abstract:
The mutagenicity of diphenylhydantoin (DPH) and its major metabolite, 5-(p-hydroxyphenyl)-5-phenylhydantoin (HPPH), has been re-evaluated by the Ames test using Salmonella typhimurium and, for DPH only, by an in vitro cytogenetic test with human lymphocytes and a turbidimetric assay of tubulin polymerization. As negative results were obtained in all test systems used here, one has to conclude that DPH is devoid of mutagenic properties.
Insights
Diphenylhydantoin (DPH) and its metabolite HPPH were tested for mutagenicity. All assays, including the Ames test, showed no mutagenic properties for DPH.
Area of Science:
- Pharmacology and Toxicology
- Genetics and Molecular Biology
Background:
- Diphenylhydantoin (DPH) is an anticonvulsant drug with a known therapeutic profile.
- Concerns regarding the potential mutagenicity of DPH and its metabolites necessitate rigorous evaluation.
Purpose of the Study:
- To re-evaluate the mutagenicity of diphenylhydantoin (DPH) and its primary metabolite, 5-(p-hydroxyphenyl)-5-phenylhydantoin (HPPH).
- To assess the genotoxic potential of DPH using multiple in vitro test systems.
Main Methods:
- Ames test using Salmonella typhimurium for both DPH and HPPH.
- In vitro cytogenetic assay with human lymphocytes for DPH.
- Turbidimetric assay of tubulin polymerization for DPH.
Main Results:
- All conducted test systems yielded negative results for mutagenicity.
- Diphenylhydantoin (DPH) did not induce gene mutations in the Ames test.
- No chromosomal aberrations were observed in human lymphocytes treated with DPH.
Conclusions:
- Diphenylhydantoin (DPH) is devoid of mutagenic properties based on the evaluated test systems.
- The findings suggest a lack of genotoxic risk associated with DPH exposure.