[Comparison of the teratogenic properties manifested in BALB c mice, by diphenylhydantoin and deuterated diphenylhydantoin].

The aim of this study was to investigate the role of an arene oxide pathway in the teratogenicity displayed by DPH, a highly effective antiepileptic agent. This approach was carried out by comparing the teratogene potential of DPH and of p2-H-DPH administrated at days 8, 9 and 12 of gestation. The present findings support the hypothesis that substitution of protium by deuterium at the para position of one of the phenyl rings, which favours an arene oxide pathway, causes an increase in some to the teratogenic effects of DPH.

Mutagenic and leukemogenic activity of haloperidol: a negative study.

The mutagenic and leukemogenic potential of haloperidol, a neuroleptic of the butyrophenone class, has been studied in an in vitro Ames Salmonella/microsome test and in an 18-month carcinogenicity study in mice. Three variants of the Salmonella mutation assay were included: the spot test, the standard plate incorporation test and the preincubation test. There was no evidence that haloperidol had any mutagenic activity in any of the Salmonella mutation tests with any of the Salmonella typhimurium tester strains in the presence or absence of Aroclor 1254-induced rat- or mouse-liver S9-mix.

Population monitoring for genetic damage induced by environmental physical and chemical agents.

The short-term tests performed in vitro on different systems, from phage to human cells, or in vivo, on laboratory animals, allow only a qualitative estimate of the action of mutagenic agents, and the extrapolation of such experimental results to man may encounter many difficulties.Direct biomonitoring of populations exposed to chemicals could represent a more realistic approach for an evaluation of the hazards to man. Certain methods are still under development.

Metabolism and mutagenicity of acrylonitrile: an in vivo study.

The mutagenic activity present in urine of animals treated with acrylonitrile (ACN) is tentatively related to the excretion of three urinary metabolites: thiocyanate (SCN-), hydroxyethylmercapturic acid (OH-MA), and cyanoethylmercapturic acid (CN-MA). It is shown that the route of administration and animal species affect SCN- excretion but not the excretion of hydroxyethyl- and cyanoethylmercapturic acids or the mutagenicity of urine from ACN-treated animals. Various pretreatments (phenobarbital, CoCl2, diethylmaleate, trichloroacetonitrile) decrease the mutagenicity of urine from ACN-treated animals and decrease the excretion of SCN- and OH-MA.