Pollution from drug manufacturing: review and perspectives

Abstract

As long ago as the sixteenth century, Paracelsus recognized that ‘the dose makes the poison’. Indeed, environmental concentrations of pharmaceuticals excreted by humans are limited, most importantly because a defined dose is given to just a fraction of the population. By contrast, recent studies have identified direct emission from drug manufacturing as a source of much higher environmental discharges that, in some cases, greatly exceed toxic threshold concentrations. Because production is concentrated in specific locations, the risks are not linked to usage patterns. Furthermore, as the drugs are not consumed, metabolism in the human body does not reduce concentrations. The environmental risks associated with manufacturing therefore comprise a different, wider set of pharmaceuticals compared with those associated with risks from excretion. Although pollution from manufacturing is less widespread, discharges that promote the development of drug-resistant microorganisms can still have global consequences. Risk management also differs between production and excretion in terms of accountability, incentive creation, legal opportunities, substitution possibilities and costs. Herein, I review studies about industrial emissions of pharmaceuticals and the effects associated with exposure to such effluents. I contrast environmental pollution due to manufacturing with that due to excretion in terms of their risks and management and highlight some recent initiatives.

Potential ecological footprints of active pharmaceutical ingredients: an examination of risk factors in low-, middle- and high-income countries

“…The presence of industrial wastewater in the sewage stream can be a significant contributor to the environmental load of APIs not only in lower income nations [60,62], but also globally [15,65]. A companion paper in this issue [15] discusses this aspect in the global context and demonstrates the point-source pollution implications of the API manufacturing sector.…”

“…APIs used to treat diseases in humans (and animals) can enter the natural environment during the manufacturing process [15] or, following therapeutic use, via some form of wastewater collection and treatment system [16]. The excretion or application of animal manures to agricultural land or waterways occur following veterinary/aquaculture use [17,18].…”

Medicating the environment: assessing risks of pharmaceuticals to wildlife and ecosystems

“…Recycled raw sewage, municipal wastewater and biosolids are also being applied increasingly to urban green spaces such as parks and golf courses, which is likely to result in increased environmental exposure to organisms occurring across a range of habitats [14,33,34]. Pharmaceuticals also have been detected at high concentrations near drug production facilities, particularly in countries with developing economies [2]. Using modern analytical techniques pioneered by some of the authors featured in this Theme Issue, a range of pharmaceuticals, including synthetic hormones, anti-inflammatories and antidepressants have recently been detected in soils, surface waters, sediments, groundwaters and in marine ecosystems [12,22,32].…”

“…Despite environmental risk assessment procedures being established as part of the registration and approval of pharmaceuticals, there is a legacy of existing, untested products in use globally. There is also a lack of environmental monitoring and regulation, in both developed and developing countries, with regard to the release of APIs from manufacturing and also via effluent and sewage sludge from WWTPs [2]. This Theme Issue has the potential to provide much needed evidence for improving or tailoring the environmental risk assessment of pharmaceuticals by considering the vulnerability of wildlife to exposure and adverse effects, based on their ecology and physiology [16].…”

“…With this comes an increase in the quantity and diversity of pharmaceuticals consumed and subsequently excreted. Significant quantities of pharmaceuticals can be emitted to the environment from manufacturing sites (particularly, but not exclusively, in lower income countries, reviewed by Larsson [2]), in addition to those released via inadequately treated sewage [3]. Different types of pharmaceuticals also are commonly used to enhance livestock production in both high-and low-income countries, sometimes without strong regulatory controls for use or discharge.…”