Toxicological and ecotoxicological risk‐based prioritization of pharmaceuticals in the natural environment

Abstract

Approximately 1500 active pharmaceutical ingredients are currently in use; however, the environmental occurrence and impacts of only a small proportion of these have been investigated. Recognizing that it would be impractical to monitor and assess all pharmaceuticals that are in use, several previous studies have proposed the use of prioritization approaches to identify substances of most concern so that resources can be focused on these. All of these previous approaches suffer from limitations. In the present study, the authors draw on experience from previous prioritization exercises and present a holistic approach for prioritizing pharmaceuticals in the environment in terms of risks to aquatic and soil organisms, avian and mammalian wildlife, and humans. The approach considers both apical ecotoxicological endpoints as well as potential nonapical effects related to the therapeutic mode of action. Application of the approach is illustrated for 146 active pharmaceuticals that are used either in the community or in hospital settings in the United Kingdom. Using the approach, 16 compounds were identified as a potential priority. These substances include compounds belonging to the antibiotic, antidepressant, anti-inflammatory, antidiabetic, antiobesity, and estrogen classes as well as associated metabolites. In the future, the prioritization approach should be applied more broadly around the different regions of the world. Environ Toxicol Chem 2016;35:1550-1559. © 2016 SETAC.

Are exposure predictions, used for the prioritization of pharmaceuticals in the environment, fit for purpose?

“…This was not reflected for all over-the-counter pharmaceuticals, similarly to a recent study in Canada [28]. This highlights the need for a new approach to incorporate over-thecounter consumption into WWTP pharmaceutical loadings [4,27]. The results from the River Ouse ( Figure 5) are more complicated, a mixture of both over-the-counter and prescription-only pharmaceuticals had MECs that were greater than the PEC (worst case) estimates.…”

Impacts of compound properties and sediment characteristics on the sorption behaviour of pharmaceuticals in aquatic systems

“…The specific objectives were to: 1) explore the effects of sediment type on the sorption behaviour of a range pharmaceuticals with different properties; 2) evaluate the suitability of existing predictive models for ionsible compounds for use on pharmaceuticals in sediments; and 3) develop improved models for estimating the sorption behaviour of pharmaceuticals in different sediment types. The study was performed using five pharmaceuticals chosen based on a risk-based screening studies in aquatic and terrestrial systems that was performed by our group to identify the pharmaceuticals of most concern in environment in the UK [64] and Iraq [65]. The compounds varied in their physicochemical properties.…”

Application of prioritization approaches to optimize environmental monitoring and testing of pharmaceuticals

“…The most common approach to risk-based prioritization is to calculate a risk-quotient (RQ), Other risk-based methods focused on assessment of risks to predators or humans posed by secondary poisoning via exposure from food or water. In the case of human unintended exposure, the acceptable daily intake (ADI) is typically used to derive the PNEC ( These PECs and MECs are generally applied to entire countries or regions (Guo et al 2016). Highertier spatial PEC modelling approaches might also be used.…”

“…In terms of the PNEC (Table 2), experimental ecotoxicity data for pharmaceuticals is limited and to compensate for this, models are extensively utilized which may be inappropriate for all or for specific groups of pharmaceuticals and/or have yet to be validated for drugs specifically. ECOSAR was commonly cited as the source of modelled ecotoxicity data despite many compounds falling outside its applicability domain (Dong et al 2013;Guo et al 2016;Ortiz de García et al 2013). In addition, the relevance to pharmaceuticals is questionable as ECOSAR was originally validated using a small set of industrial chemicals with simple molecular structures dissimilar to those of drugs and mainly acting via a non-specific narcosis mode of action (Sangion and Gramatica 2016;Sanderson et al 2004).…”

“…A variety of prioritization approaches were suggested, which employ different methodologies (Dong et al 2013;Kumar and Xagoraraki 2010;Diamond et al 2011;Besse et al 2012;Fick et al 2010;Ortiz de García et al 2013, Guo et al 2016. Many of these approaches are limited in scope in terms of both number of compounds included and environmental exposure routes considered.…”