Vestel, Jessica. Determination of endocrine disruption risk following exposure to betamethasone in surface and drinking water. Retrieved from https://doi.org/doi:10.7282/T3G44SG4
DescriptionTo date, the presence of synthetic glucocorticosteroids in surface water and their potential endocrine disruption activity at environmental concentrations has not been fully investigated. Synthetic glucocorticosteroids (GC) may interfere with endogenous GC receptors within the hypothalamic-pituitary-gonadal (HPG) axis and disruptions of this pathway can result in decreased reproduction and/or adverse developmental effects in offspring. Much of the evidence for endocrine disruption in wildlife populations has been derived from aquatic animals such as fish, due to widespread contamination of surface water. The HPG axis is phylogenetically conserved across all vertebrate species and fish have the advantage over mammals as an experimental model of reaching maturity relatively quickly and have overall shorter life spans, which make them ideal for life cycle toxicology studies. Betamethasone, a synthetic glucocorticosteroid, has been on the market in the United States since the 1980’s and is on the World Health Organization Model List of Essential Medicines. Betamethasone mimics the action of cortisol and may disrupt the HPG axis. Studying fish for the endocrine disruption potential of betamethasone is logical, as they could be exposed to pharmaceuticals in waste water treatment plant effluent following normal patient use and excretion. In the present study, the Pharmaceutical Assessment and Transport Evaluation (PhATE) model estimated betamethasone concentrations to be <0.6 ng/L in 95% of all surface waters and <0.1 ng/L for 95% of the U.S. population. Environmentally relevant concentrations were then used in a two generation fish full life cycle (FFLC) study with Japanese medaka. Gross endpoints were evaluated, as well as secondary sexual characteristics and vitellogenin expression. The highest concentration at which no endocrine disruption outcomes are anticipated (NOEC) was determined to be 0.1 µg/L and a reference dose of 7 x 10-5 µg/kg-day for humans was derived from the NOEC. The average daily dose to humans was estimated from surface and drinking water concentrations and calculated margins of safety ranging from three to thirty indicate no adverse effects are anticipated from exposures to betamethasone at environmentally relevant concentrations.