Complex Mixtures, Complex Responses—Using Comprehensive Approaches to Assess Pharmaceutical Effects on Fish

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Prescription pharmaceuticals have been found in streams and lakes throughout the United States. They enter aquatic ecosystems primarily through treated municipal wastewater treatment plant (WWTP) effluent following human excretion or disposal of unwanted pharmaceuticals into the sewer system. Pharmaceuticals and their transformation products are generally present in low concentrations (less than 100 nanograms per liter) in most treated municipal wastewater effluents, but according to previous U.S. Geological Survey (USGS) research, they can be locally elevated in the effluent at WWTPs that receive incoming waste from pharmaceutical formulation facilities.

The present collaborative study between St. Cloud State University and USGS scientists used a comprehensive set of biological endpoints and minnow life stages in laboratory and field exposures to better understand the effects of pharmaceuticals on larval and adult fathead minnows (Pimephales promelas). This type of minnow was chosen because they are a common laboratory model for studies of this kind and are also an ecologically important species present throughout North America.

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Larval and adult fathead minnows were exposed to treated municipal effluent from a WWTP known to receive input from a pharmaceutical formulation facility. In addition, both life stages were also exposed in the laboratory to the following nine pharmaceuticals individually or in mixtures: temazepam, a sleep aid; methocarbamol, a muscle relaxant; tramadol, an opioid agonist; hydrocodone, methadone, and oxycodone, opioids; and fluoxetine, paroxetine, and venlafaxine-antidepressants. The selected pharmaceuticals and corresponding exposure levels were guided by the previous USGS research.

The complexity of the effluent and laboratory exposures resulted in comparable complex biological responses. Juvenile fathead minnows exposed to the chemicals suffered from reduced growth and altered escape behavior. The altered escape behavior means that, when faced with a threat, the minnows did not escape as efficiently as they normally would, which could potentially increase the chances they would be eaten and could ultimately translate to population-level effects.

Adult fish reacted differently than juvenile fish to exposures. Adult females exposed to a mixture of the pharmaceuticals generally experienced an increase in relative liver size compared to control females, which suggests that the liver is reacting to pharmaceutical exposure. Adult males exposed to the pharmaceuticals had a variety of reactions. Most did not defend their nests as rigorously as those that were not exposed to the pharmaceuticals. The males exposed to WWTP effluent in the field component of this research produced a chemical known as plasma vitellogenin, a protein associated with egg production in females and not present in male fish under normal conditions.

This study documents that treated effluent containing pharmaceuticals and exposures to pharmaceuticals in a laboratory study can affect fish behavior and other biological endpoints. This study highlights the importance of including diverse biological endpoints spanning levels of biological organization and life stages when assessing the effects of pharmaceuticals. The environmental concentrations of prescription pharmaceuticals are usually below human or domestic animal therapeutic concentrations; however, these lower concentrations may still have effects on aquatic organisms that are exposed on a continual basis.

This study is part of a long-term effort by the USGS Toxic Substances Hydrology Program to determine the fate and effects of contaminants of emerging concern and to provide water-resource managers with objective information that assists in the development of effective water management practices. Understanding the impacts of environmental pharmaceutical occurrence in aquatic ecosystems may allow for effective strategies to reduce organism exposures.

This research was funded by the USGS Ecosystems Mission Area’s Environmental Health Program (Contaminant Biology and Toxic Substances Hydrology) and supported by the National Science Foundation (CBET 1336062).