A comprehensive aquatic risk assessment of the beta-blocker propranolol, based on the results of over 600 research papers.

A comprehensive aquatic environmental risk assessment (ERA) of the human pharmaceutical propranolol was conducted, based on all available scientific literature. Over 200 papers provided information on environmental concentrations (77 of which provided river concentrations) and 98 dealt with potential environmental effects. The median concentration of propranolol in rivers was 7.1 ng/L (range of median values of individual studies 0.07 to 89 ng/L), and the highest individual value was 590 ng/L. Sixty-eight EC50 values for 35 species were available. The lowest EC50 value was 0.084 mg/L. A species sensitivity distribution (SSD) provided an HC50 value of 6.64 mg/L and an HC5 value of 0.22 mg/L. Thus, there was a difference of nearly 6 orders of magnitude between the median river concentration and the HC50 value, and over 4 orders of magnitude between the median river concentration and the HC5 value. Even if an assessment factor of 100 was applied to the HC5 value, to provide considerable protection to all species, the safety margin is over 100-fold. However, nearly half of all papers reporting effects of propranolol did not provide an EC50 value. Some reported that very low concentrations of propranolol caused effects. The lowest concentration reported to cause an effect - in fact, a range of biochemical and physiological effects on mussels - was 0.3 ng/L. In none of these 'low concentration' papers was a sigmoidal concentration-response relationship obtained. Although inclusion of data from these papers in the ERA cause a change in the conclusion reached, we are sceptical of the repeatability of these 'low concentration' results. We conclude that concentrations of propranolol present currently in rivers throughout the world do not constitute a risk to aquatic organisms. We discuss the need to improve the quality of ecotoxicology research so that more robust ERAs acceptable to all stakeholders can be completed.
Competing Interests: Declaration of competing interest This study was partially funded by the pharmaceutical company AstraZeneca, and one of the authors (SFO) is an employee of that company. However, the literature searches, identification of relevant research, extraction of information, and writing the complete first draft of the paper were all conducted entirely by the university-based authors, with no interference from any employee of AstraZeneca. SFO and other employees of AstraZeneca subsequently improved that initial draft, but none of the data, or their interpretation, were changed during that process.
(Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)