Environmental fate and effects assessment of human pharmaceuticals: lessons learnt from regulatory data

Simon Schwarz,Daniela Gildemeister,Jean Bachmann,Patrick Schröder,Arne Hein

doi:10.1186/s12302-021-00503-0

Abstract

Human pharmaceuticals are extensively studied and assessed before marketing approval. Since 2006, this also includes an assessment of environmental risks. In the European Union, this is based on the guideline on the environmental risk assessment of medicinal products for human use (EMEA/CHMP/SWP/4447/00 corr 2), which is currently under revision. For Germany, the German Environment Agency (UBA) is tasked with the evaluation of environmental risks of human pharmaceuticals. Applicants seeking approval of medicinal products need to submit fate and effect data, in case predicted environmental concentrations (PECs) exceed 10 ng/L in surface waters, or the substance is of specific concern through its mode of action or physico-chemical characteristics.Over the last decade, this regulatory work resulted in an internal agency database containing effect data on approximately 300 active pharmaceutical ingredients (APIs). A considerable part of this data is currently not publicly available due to property rights held by the respective applicants. The database was evaluated to draw conclusions on how the current assessment approach may be improved.The evaluation of aquatic effect data shows considerable variation in ecotoxic effect concentrations, but supports the current use of 10 ng/L as PEC action limit. For endocrine-active substances and antibiotics, a clear sensitivity profile was observed, which allows a more targeted assessment in the future. The conclusions drawn from terrestrial effect data are less clear, as the database itself is biased because information is only available for substances with high sorption. Further adaptations of the terrestrial assessment strategy, including action triggers, appear necessary. Fate data show a high persistence of many APIs: approximately 43% of all APIs are classified as very persistent; 12% of these show DT50 values in a range where abiotic or biotic degradation is not expected.Overall, the evaluation has shown that improvements of the current guideline are possible.

Highlights

Pharmaceuticals as environmental contaminants Pharmaceutical residues are widely recognised as contaminants in the environment [1–3]
European legislation has recognised the problem of pharmaceuticals in the environment and Article 8(3) of Directive 2001/83/EC demands the assessment of environmental risks in the authorisation process of human medicinal products [9]
For 87 Active pharmaceutical ingredient (API) the no observed effect concentration (NOEC) or E C10 was lower than 0.01 mg/L, the threshold for a substance to be classified as “toxic” (T) in PBT assessment according to the REACH Regulation [51]

Summary

Introduction

Pharmaceuticals as environmental contaminants Pharmaceutical residues are widely recognised as contaminants in the environment [1–3]. Various active pharmaceutical ingredients (APIs) applied in human or Schwarz et al Environ Sci Eur (2021) 33:68 veterinary medicine are frequently found in the environment [4]. European legislation has recognised the problem of pharmaceuticals in the environment and Article 8(3) of Directive 2001/83/EC demands the assessment of environmental risks in the authorisation process of human medicinal products [9]. For the European Union, the “Guideline on the environmental risk assessment of medicinal products for human use” [10] describes the current requirement of an environmental risk assessment (ERA) for human pharmaceuticals. Environmental issues concerning pharmaceuticals are still of great interest in the EU, the outcome of the environmental risk assessment is not part of the benefit–risk assessment in the authorisation procedure for human pharmaceuticals

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