title: The read-across hypothesis and environmental risk assessment of pharmaceuticals.
abstract: Pharmaceuticals in the environment have received increased attention over the past decade, as they are ubiquitous in rivers and waterways. Concentrations are in sub-ng to low μg/L, well below acute toxic levels, but there are uncertainties regarding the effects of chronic exposures and there is a need to prioritise which pharmaceuticals may be of concern. The read-across hypothesis stipulates that a drug will have an effect in non-target organisms only if the molecular targets such as receptors and enzymes have been conserved, resulting in a (specific) pharmacological effect only if plasma concentrations are similar to human therapeutic concentrations. If this holds true for different classes of pharmaceuticals, it should be possible to predict the potential environmental impact from information obtained during the drug development process. This paper critically reviews the evidence for read-across, and finds that few studies include plasma concentrations and mode of action based effects. Thus, despite a large number of apparently relevant papers and a general acceptance of the hypothesis, there is an absence of documented evidence. There is a need for large-scale studies to generate robust data for testing the read-across hypothesis and developing predictive models, the only feasible approach to protecting the environment.
authors.affiliation: Biosciences, School of Health Sciences and Social Care, Brunel University , Uxbridge, Middlesex, UB8 3PH, United Kingdom.
authors.forename: Mariann
authors.initials: M
authors.lastname: Rand-Weaver
authors.forename: Luigi
authors.initials: L
authors.lastname: Margiotta-Casaluci
authors.forename: Alpa
authors.initials: A
authors.lastname: Patel
authors.forename: Grace H
authors.initials: GH
authors.lastname: Panter
authors.forename: Stewart F
authors.initials: SF
authors.lastname: Owen
authors.forename: John P
authors.initials: JP
authors.lastname: Sumpter
mesh_terms: D000818:Animals; D055669:Ecological and Environmental Phenomena; D006801:Humans; D008962:Models, Theoretical; D004364:Pharmaceutical Preparations / Q000032:analysis*; D018570:Risk Assessment
chemical_list: D004364:Pharmaceutical Preparations