Lack of mutagenicity of diphenylhydantoin in in vitro short-term tests

https://doi.org/10.1016/0165-1218(84)90095-8Get rights and content

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.

References (38)

  • J. South

    Teratogenic effect of anticonvulsants

    Lancet

    (1972)
  • B.D. Speidel et al.

    Maternal epilepsy and abnormalities of the fetus and newborn

    Lancet

    (1972)
  • M.A. Stenchever et al.

    Diphenylhydantoin: Effect on the chromosomes of human leukocytes

    Am. J. Obstet. Gynecol.

    (1971)
  • B.N. Ames et al.

    An improved bacterial test system for the detection and classification of mutagens and carcinogens

  • B.N. Ames et al.

    Methods for detecting carcinogens and mutagens with the Salmonella/mammalian-microsome mutagenicity test

    Mutation Res.

    (1975)
  • G.R. De Vore et al.

    Phenytoin: An evaluation of several potential teratogenic mechanisms

    Epilepsia

    (1977)
  • A.R. Fazel et al.

    Phenytoin-induced cardiac malformation in A/J mice

    Teratology

    (1980)
  • R.H. Finnel

    Phenytoin-induced teratogenesis: A mouse model

    Science

    (1981)
  • J.E. Gibson et al.

    Teratogenic effects of diphenylhydantoin in Swiss-Webster and A/J mice

  • Cited by (14)

    • Phenytoin – An anti-seizure drug: Overview of its chemistry, pharmacology and toxicology

      2020, Food and Chemical Toxicology
      Citation Excerpt :

      Data on mutagenicity, carcinogenicity, and teratogenicity are provided in separate subchapters. The mutagenicity of phenytoin and the mutagenicity of its major metabolite, 5-(4-hydroxyphenyl)-5-phenylhydantoin (HPPH), have been tested in vitro on different Salmonella typhimurium strains (TA1535, TA100, TA1537, TA1538, TA98) using an Ames test (Sezzano et al., 1982; Léonard et al., 1984; Riedel and Obe, 1984). From the results of these studies, it was concluded that phenytoin does not have mutagenic properties.

    • The genotoxicity of ambient outdoor air, a review: Salmonella mutagenicity

      2004, Mutation Research - Reviews in Mutation Research
    View all citing articles on Scopus
    View full text