Developmental exposure to fenproporex: reproductive and morphological evaluation.

This study was designed to evaluate the maternal toxicity and teratogenicity of fenproporex, one of the most widely-used anorectic drugs in many countries, including Brazil. Three periods of exposure were evaluated: (a) 30 days before mating; (b) from gestational day (GD) 0 to 14; and (c) 30 days before mating and during pregnancy, until GD 14. Female mice from experimental groups received, by gavage, 15 mg/kg of fenproporex. Treatment with fenproporex increased ambulation of dams in the open-field test and did not influence the mobility in the forced-swimming test. There was no significant difference in maternal weight gain between the controls and fenproporex-treated groups, although fenproporex treatment reduced the gravid uterus weight. No significant difference was observed in postimplantation loss, fetal viability and sex ratio. In addition, this compound did not impair intra-uterine growth. The reduction in the number of implantations in the groups receiving fenproporex indicates that this drug may have an adverse effect on implantation. Fenproporex treatment also increased the number of fetuses presenting small kidneys and cervical ribs. The present results indicate that fenproporex, in the dose and exposure periods tested, appears to exhibit a low maternal toxicity and teratogenic potential in mice.

Behavioral neurotoxicity in adolescent and adult mice exposed to fenproporex during pregnancy.

We investigated the effects of gestational exposure to fenproporex, one of the most used anorectic drugs in Brazil, on the behavior of adolescent and adult pups (30 and 60 days of age, respectively). Pregnant Swiss mice were treated daily, by gavage, with 15 mg/kg of fenproporex chloride or water during the whole gestational period. Male pups were submitted to open-field, forced swimming test, tail suspension test and fenproporex-induced stereotyped behavior. The results demonstrated that gestational exposure to fenproporex induces antidepressant-like effect and decreases fenproporex-induced stereotyped behavior in both adolescent and adult pups. Moreover, fenproporex-exposed adolescent pups tended (P= 0.06) to be more active than control pups. Our data show, for the first time, that gestational exposure to fenproporex leads to long-lasting behavioral toxicity in male mice characteristic of altered dopaminergic transmission.