Late Gestational Exposure to the Fungicide Prochloraz: MATERIALS AND METHODS(1)



We used prochloraz (45631; Riedel-deHaen; lot 9060X, CAS 06774709-5, [C15H16Cl3N3O2] 99.4% pure by high-performance liquid chromatography, formula weight 376.67 g/mol), corn oil (C 8267; Sigma Chemical Co., St. Louis, MO; lot 81K2204, CAS 8001-30-7, density = 0.9 g/ ml), and dihydrotestosterone (DHT; Sigma; >99% purity). Hydroxyflu-tamide was provided by R.O. Neri (Schering Corp., Bloomfield, NJ).

Late Gestational Exposure to the Fungicide Prochloraz: INTRODUCTION(2)

Neither PZ nor its metabolites 2,4,6-trich-lorophenoxyacetic acid and 2,4,6-trichlorophenol affect androgen receptor (AR)-dependent gene expression in transfected cells.

In the fetal male rat, maternal PZ treatment inhibits testosterone production and increases progesterone production, indicating an inhibition of P450 17,20 lyase activity.

Late Gestational Exposure to the Fungicide Prochloraz: INTRODUCTION(1)


Prochloraz (1-{ Af-propyl-Af-[2-(2,4,6-trichlorophenoxy) ethyl]} carbamoylimidazole), or PZ, is a broad-spectrum fungicide containing an imidazole moiety that has P450-dependent demethylase activity shared by many other imidazole and imidazole-like fungicides that inhibits the conversion of lanosterol to ergosterol in fungi. Imidazole fungicides can also affect activities of several P450-dependent enzymes in vertebrates, including aromatase, 170-hydroxylase, and 17,20 lyase activity.