On the meta-analysis of hormetic effects

This review identifies understudied areas of emerging contaminant (EC) research in wastewaters and the environment, and recommends direction for future monitoring. Non-regulated trace organic ECs including pharmaceuticals, illicit drugs and personal care products are focused on due to ongoing policy initiatives and the expectant broadening of environmental legislation. These ECs are ubiquitous in the aquatic environment, mainly derived from the discharge of municipal wastewater effluents. Their presence is of concern due to the possible ecological impact (e.g., endocrine disruption) to biota within the environment. To better understand their fate in wastewaters and in the environment, a standardised approach to sampling is needed. This ensures representative data is attained and facilitates a better understanding of spatial and temporal trends of EC occurrence. During wastewater treatment, there is a lack of suspended particulate matter analysis due to further preparation requirements and a lack of good analytical approaches. This results in the under-reporting of several ECs entering wastewater treatment works (WwTWs) and the aquatic environment. Also, sludge can act as a concentrating medium for some chemicals during wastewater treatment. The majority of treated sludge is applied directly to agricultural land without analysis for ECs. As a result there is a paucity of information on the fate of ECs in soils and consequently, there has been no driver to investigate the toxicity to exposed terrestrial organisms. Therefore a more holistic approach to environmental monitoring is required, such that the fate and impact of ECs in all exposed environmental compartments are studied. The traditional analytical approach of applying targeted screening with low resolution mass spectrometry (e.g., triple quadrupoles) results in numerous chemicals such as transformation products going undetected. These can exhibit similar toxicity to the parent EC, demonstrating the necessity of using an integrated analytical approach which compliments targeted and non-targeted screening with biological assays to measure ecological impact. With respect to current toxicity testing protocols, failure to consider the enantiomeric distribution of chiral compounds found in the environment, and the possible toxicological differences between enantiomers is concerning. Such information is essential for the development of more accurate environmental risk assessment.

Hormesis is a term used by toxicologists to refer to a biphasic dose-response to an environmental agent characterized by a low dose stimulation or beneficial effect and a high dose inhibitory or toxic effect. In the fields of biology and medicine hormesis is defined as an adaptive response of cells and organisms to a moderate (usually intermittent) stress. Examples include ischemic preconditioning, exercise, dietary energy restriction and exposures to low doses of certain phytochemicals. Recent findings have elucidated the cellular signaling pathways and molecular mechanisms that mediate hormetic responses which typically involve enzymes such as kinases and deacetylases, and transcription factors such as Nrf-2 and NF-kappaB. As a result, cells increase their production of cytoprotective and restorative proteins including growth factors, phase 2 and antioxidant enzymes, and protein chaperones. A better understanding of hormesis mechanisms at the cellular and molecular levels is leading to and to novel approaches for the prevention and treatment of many different diseases.

Despite growing evidence of the deleterious effects on ecological and human health, little is known regarding the global occurrence of pharmaceuticals in rivers. Studies assessing their occurrence are available for 75 of 196 countries, with most research conducted in North America and Western Europe. This leaves large geographical regions relatively unstudied. Here, we present the findings of a global reconnaissance of pharmaceutical pollution in rivers. The study monitored 1,052 sampling sites along 258 rivers in 104 countries of all continents, thus representing the pharmaceutical fingerprint of 471.4 million people. We show that the presence of these contaminants in surface water poses a threat to environmental and/or human health in more than a quarter of the studied locations globally. Environmental exposure to active pharmaceutical ingredients (APIs) can have negative effects on the health of ecosystems and humans. While numerous studies have monitored APIs in rivers, these employ different analytical methods, measure different APIs, and have ignored many of the countries of the world. This makes it difficult to quantify the scale of the problem from a global perspective. Furthermore, comparison of the existing data, generated for different studies/regions/continents, is challenging due to the vast differences between the analytical methodologies employed. Here, we present a global-scale study of API pollution in 258 of the world’s rivers, representing the environmental influence of 471.4 million people across 137 geographic regions. Samples were obtained from 1,052 locations in 104 countries (representing all continents and 36 countries not previously studied for API contamination) and analyzed for 61 APIs. Highest cumulative API concentrations were observed in sub-Saharan Africa, south Asia, and South America. The most contaminated sites were in low- to middle-income countries and were associated with areas with poor wastewater and waste management infrastructure and pharmaceutical manufacturing. The most frequently detected APIs were carbamazepine, metformin, and caffeine (a compound also arising from lifestyle use), which were detected at over half of the sites monitored. Concentrations of at least one API at 25.7% of the sampling sites were greater than concentrations considered safe for aquatic organisms, or which are of concern in terms of selection for antimicrobial resistance. Therefore, pharmaceutical pollution poses a global threat to environmental and human health, as well as to delivery of the United Nations Sustainable Development Goals.