the potential long-term effects of the product in the environment, regardless of its
environmental exposure concentration. Depending on the results obtained in the
Phase I (screening phase), a more detailed and definitive assessment is performed in
Phase II.
To conclude, and despite recognizing that the implementation of the ERA procedures has constituted a relevant progress to prevent the environmental undesirable
effects of pharmaceuticals, some limiting aspects are worth to be mentioned:
– Even though that the presentation of an ERA is mandatory in the registration of a
drug, the final authorization or refusal does not depend on the ERA itself.
– ERAs are compulsory for new drugs, but not for those authorized before the
approval of the Directive 2001/83/EC.
– ERAs are conducted with pharmaceutical products rather than with drugs.
6 Presence of Pharmaceuticals in Wastewater
The presence of pharmaceuticals in treated wastewater, surface water, and other
freshwater resources is a common phenomenon at a global level that has been
documented for almost four decades [24–32]. As seen before, drugs and metabolites
are excreted and reach wastewater treatment plants (WWTPs) [30, 33–48]. Drugs for
human use are the main source in wastewater, whereas hospital wastes are the
second largest source. Discharges from drug manufacturers are of minor
relevance [32].
The persistence of pharmaceutical compounds in wastewater (or pseudopersistence) is mainly due their continuous release into the WWTPs. Although the
total amount is affected by the continuous degradation wastewater treatment processes, their continuous inputs in small quantities due to multiple sources, cause
many pharmaceutical products remain in the aquatic environment for long periods of
time [49–53]. For example, some pharmaceuticals such as carbamazepine, clofibric
acid, diclofenac, naproxen, sulfamethoxazole, and lamotrigine can pass the treatment in WWTPs. Once in the aquatic environment, naproxen and sulfamethoxazole
can resist up to 1 year in nature being biologically active, while clofibric acid can be
maintained in its original form for several years [32].
The most frequently detected families of pharmaceuticals in wastewater worldwide are antibiotics, analgesics, blood lipid regulators, cardiovascular drugs, and
antidepressants. For example, while the highest amount of antibiotics was detected
in Asia, the highest amount of painkillers was detected in Europe, and the highest
concentration of antidepressants was measured in North America [24, 54]. Currently,
of the approximately 1,500 pharmaceutical ingredients most used and studied in total
(which represent only a limited portion of the total) [55], nearly 560 different
compounds have been effectively detected globally in wastewater [24]. Figure 3
shows the total concentrations of several families of drugs detected in European
WWTPs since 2010. Analgesics/anti-inflammatory drugs, β-blocker agents, drugs
The Journey of Human Drugs from Their Design at the Bench to Their Fate in Crops
17
environmental exposure concentration. Depending on the results obtained in the
Phase I (screening phase), a more detailed and definitive assessment is performed in
Phase II.
To conclude, and despite recognizing that the implementation of the ERA procedures has constituted a relevant progress to prevent the environmental undesirable
effects of pharmaceuticals, some limiting aspects are worth to be mentioned:
– Even though that the presentation of an ERA is mandatory in the registration of a
drug, the final authorization or refusal does not depend on the ERA itself.
– ERAs are compulsory for new drugs, but not for those authorized before the
approval of the Directive 2001/83/EC.
– ERAs are conducted with pharmaceutical products rather than with drugs.
6 Presence of Pharmaceuticals in Wastewater
The presence of pharmaceuticals in treated wastewater, surface water, and other
freshwater resources is a common phenomenon at a global level that has been
documented for almost four decades [24–32]. As seen before, drugs and metabolites
are excreted and reach wastewater treatment plants (WWTPs) [30, 33–48]. Drugs for
human use are the main source in wastewater, whereas hospital wastes are the
second largest source. Discharges from drug manufacturers are of minor
relevance [32].
The persistence of pharmaceutical compounds in wastewater (or pseudopersistence) is mainly due their continuous release into the WWTPs. Although the
total amount is affected by the continuous degradation wastewater treatment processes, their continuous inputs in small quantities due to multiple sources, cause
many pharmaceutical products remain in the aquatic environment for long periods of
time [49–53]. For example, some pharmaceuticals such as carbamazepine, clofibric
acid, diclofenac, naproxen, sulfamethoxazole, and lamotrigine can pass the treatment in WWTPs. Once in the aquatic environment, naproxen and sulfamethoxazole
can resist up to 1 year in nature being biologically active, while clofibric acid can be
maintained in its original form for several years [32].
The most frequently detected families of pharmaceuticals in wastewater worldwide are antibiotics, analgesics, blood lipid regulators, cardiovascular drugs, and
antidepressants. For example, while the highest amount of antibiotics was detected
in Asia, the highest amount of painkillers was detected in Europe, and the highest
concentration of antidepressants was measured in North America [24, 54]. Currently,
of the approximately 1,500 pharmaceutical ingredients most used and studied in total
(which represent only a limited portion of the total) [55], nearly 560 different
compounds have been effectively detected globally in wastewater [24]. Figure 3
shows the total concentrations of several families of drugs detected in European
WWTPs since 2010. Analgesics/anti-inflammatory drugs, β-blocker agents, drugs
The Journey of Human Drugs from Their Design at the Bench to Their Fate in Crops
17