Two of the main classes of pesticides commonly used in agriculture are azole fungicides and pyrethroid insecticides. Because azoles have been shown to synergize the effect of pyrethroids, the effect of their mixture is of concern. The aim of the present study was to investigate the effect of sublethal concentrations of epoxiconazole and α-cypermethrin and their mixture on growth, reproduction, and in vivo cytochrome P450 activity of the aquatic crustacean Daphnia magna over 42 d. Continuous exposure to nonlethal concentrations of α-cypermethrin at 20 ng/L negatively affected adult growth and number and size of neonates within the first 14 d of exposure. Exposure to epoxiconazole at 25 μg/L increased protein content of adults within 1 to 3 d after initiating exposure and increased cumulative number of offspring at exposure times >31 d. Epoxiconazole enhanced the negative effect of α-cypermethrin up to 3-fold leading to decreased growth, cytochrome P450 activity, and reproduction of D. magna within the first 14 d of exposure. After 14 d, the synergistic interactions disappeared. The reported effects, although lacking direct negative consequence in the long term, might have cumulative toxicity with other stressors such as food scarcity, predation, and pathogens, posing an additional hazard for the organisms at the beginning of their life cycle. Environ Toxicol Chem 2017;36:2155-2166. © 2017 SETAC.

Ca2+-signalling controls human sperm functions necessary for successful fertilization. Multiple endocrine disrupting chemicals have been found to activate the CatSper Ca2+-channel and thereby interfere with Ca2+-signalling in human sperm. Finasteride is prescribed to men in the fertile age to treat hair loss and its use has been associated with impaired male fertility. Due to the structural relatedness of finasteride to the endogenous CatSper ligand progesterone this study aimed to investigate whether finasteride affects human sperm in a progestogen-like manner. The effect of finasteride on Ca2+-signalling via CatSper in human sperm was investigated in cell suspensions and by single cell imaging. Additionally, effects on sperm penetration into viscous medium and acrosome reaction were assessed. Finasteride alone caused a minor, transient rise in the intracellular, free Ca2+ concentration ([Ca2+]i) at physiologically relevant concentrations. Ca2+-signals induced by PGE1 were inhibited by finasteride displaying mixed type of inhibition consistent with multiple binding sites. Finasteride did not interfere with progesterone-induced Ca2+-signalling and no effect on acrosome reaction or sperm viability was found. Finasteride significantly decreased PGE1-induced penetration into viscous medium, but in concentrations above what is measured in blood and seminal fluids during regular finasteride administration. In conclusion, the use of finasteride may affect Ca2+-signalling in human sperm through an interaction with the PGE1-binding site, but to which extend it alters the chances of a successful fertilization needs further investigation. It remains to be investigated whether finasteride administration may give rise to side effects by interfering with prostaglandin signalling elsewhere in the human body.

No abstract