The contraceptive active ingredient levonorgestrel disrupts the physiology of Macrocyclops albidus

Active pharmaceutical ingredients, such as levonorgestrel (LNG), continue to increase in aquatic ecosystems and are detected in environmental matrices; however, their ability to bioaccumulate and cause reproductive, developmental, and biochemical defects in benthic organisms, such as Macrocyclops albidus, is unknown. This study investigated the effects of LNG on the oxidative stress response, reproduction, and development of M. albidus. Levonorgestrel induced a significant (p < 0.05) increase in total protein with increasing concentrations from 10 ng L^-1. Intracellular hydrogen peroxide levels were elevated after exposure to LNG (p < 0.05). Malondialdehyde level declined as LNG concentration increased at day 7 and increased at higher LNG at day 14. Peroxidase activity was significantly (p < 0.05) elevated by lower (1-100 ng L^-1) than higher (1000-10000 ng L^-1) concentrations of LNG. Glutathione S-transferase activity declined with increasing concentrations of LNG. Increased metamorphosis from the nauplii to the copepodite stage was significantly induced by 1000 and 10000 ng L^-1 LNG within four days of exposure. In addition, higher concentrations of LNG induced early production of egg sacs in female M. albidus within four days. Levonorgestrel bioaccumulated in M. albidus, with higher tissue concentrations occurring at high exposures. This study revealed that LNG is readily absorbed and causes stress by interfering with reproduction and metamorphosis in M. albidus, thereby highlighting the role of this zooplankton as a sensitive bioindicator of endocrine disruptors in aquatic ecosystems.