Improved safety margin for embryotoxicity in rats for the new endoperoxide artefenomel (OZ439) as compared to artesunate.

Background: Combination medicines including an artemisinin are the mainstay of antimalarial therapy. Artemisinins are potent embryotoxicants in animal species due to their trioxane moiety.

Methods: As part of its development, the new synthetic trioxolane antimalarial artefenomel (OZ439) was tested in rat whole embryo culture and in rat embryo-fetal toxicity studies with dosing throughout organogenesis or with a single dose on Gestational Day (GD) 12.

Effects of the Oral Oxytocin Receptor Antagonist Tocolytic OBE001 on Reproduction in Rats.

Background: OBE001 is a novel, orally active nonpeptide oxytocin receptor antagonist under development for the treatment of preterm labor and improvement in embryo implantation and pregnancy rate in assisted reproductive technology (ART). The reproductive safety of OBE001 was evaluated in customized fertility embryonic development (FER)/early embryonic development (EED) and fetal development (FD) and pre/postnatal development (PPN) studies mimicking clinical exposure scenarios.

Methods: Oral OBE001 was evaluated at doses of 37.

Inhibin B as a marker of sertoli cell damage and spermatogenic disturbance in the rat.

This study was designed to determine the effects of Compound A on spermatogenesis including assessment of inhibin B levels and on fertility in the male rat over a 15 to 19 weeks treatment and a 19 weeks treatment-free period in control and 30, 60, and 180 mg/kg dose groups (n = 22/group). Compound A in a dose-dependent manner induced various degrees of spermatogenic alterations compatible with Sertoli cells being the primary target, for example, inter- and intracellular Sertoli cell vacuolization and altered cellular morphology followed by germ cell degeneration and marked reduction of epididymidal sperm numbers. Blood-testis barrier remained intact (electron microscopy and hyperosmotic fixation test) until germ cells disappeared.

Adult fathead minnow, Pimephales promelas, partial life-cycle reproductive and gonadal histopathology study with bisphenol A.

Bisphenol A (BPA) is an intermediate used to produce epoxy resins and polycarbonate plastics. Although BPA degrades rapidly in the environment with aquatic half-lives from 0.5 to 6 d, it can be found in aquatic systems because of widespread use.