Effects of the Gestagen Levonorgestrel in a Life Cycle Test with Zebrafish (Danio rerio).

The amount of pharmaceuticals transferred to the aquatic environment via municipal and hospital waste water is steadily increasing. The progress in medical research results in active substances of increased stability, specificity and potency, which can trigger adverse effects in aquatic organisms. Moreover, advanced analytical methods allow the detection of pharmaceuticals in environmental matrices at very low concentrations which increases the number of substances to be assessed. Levonorgestrel is a synthetic gestagen commonly used in medicinal products for contraception. As progestogenic compounds could have an impact on fish maturation processes, a life cycle test was conducted to assess the effects of levonorgestrel exposure of the embryonic to the adult stage of zebrafish (Danio rerio) at mean measured concentrations of 0.06, 0.16, 0.47, 1.64 and 5.45 ng/L. Apical endpoints were survival, growth, reproduction and sex ratio. Indication of endocrine modulation was completed by measurement of vitellogenin and 11-keto-testosterone in blood plasma, as well as by histopathological analysis of gonads. For all parameters, control values were within the recommended quality range. The most prominent levonorgestrel effect was the shift towards an increased number of male fish at 1.64 and especially 5.45 ng/L, where all fish were histologically determined as males and no spawning occurred; 11-keto-testosterone was significantly decreased. The NOEC of 0.47 ng levonorgestrel/L was confirmed by the fertilisation capability of adult fish, the male maturation stages and female gonad histopathology. Whereas hatch and juvenile growth were not affected, post-hatch survival was significantly impeded at ≥ 0.47 ng levonorgestrel/L, although not clearly related to the test concentration. For male length and weight the same NOEC of 0.16 ng/L was obtained at study termination. This article is protected by copyright. All rights reserved.