antiepileptic, anti-inflammatory, antidepressants, or antibiotics have been found at
concentrations ranging from a few ng/L to few mg/L in wastewater, surface water,
and groundwater worldwide [4, 6]. Although the environmental concentrations
measured in aquatic ecosystems are often quite low, pharmaceuticals are designed
to be biologically active at low concentrations; for this reason pharmaceuticals
revealed in environment might represent a potential risk for chronically exposed,
non-target organisms [3, 5]. Considering the potential hazard of pharmaceuticals
towards ecosystems some international actions have been planned. For instance, the
European Union has included 17α-ethinylestradiol, 17β-estradiol, and diclofenac to
the list of the Water Framework Directive (2013/39/EU) as priority molecules to be
monitored in aquatic ecosystems.
Nonsteroidal anti-inflammatory drugs (NSAIDs) represent one of the most relevant therapeutic class found in the aquatic ecosystems. NSAIDs are largely used for
their analgesic, antipyretic, and anti-inflammatory properties to cure pain and
inflammation. They inhibit the synthesis and the release of prostaglandins from
arachidonic acid, acting as non-selective inhibitors of cyclooxygenase enzymes,
including both the cyclooxygenase-1 (COX-1) and the cyclooxygenase-2 (COX-2)
isoforms [7]. Different NSAIDs have been prescribed extensively throughout the
world. For instance, more than 70 million prescriptions are written each year in the
United States, while considering the over-the-counter use, more than 30 billion
NSAID doses are consumed annually in the United States alone [8]. Because of
the huge, continuative and increasing use, as well as their specific pharmacokinetic
properties, NSAIDs can reach detectable concentrations both in sewage and in
surface water [9], accounting for 15% of pharmaceuticals measured in aquatic
ecosystems worldwide [4]. Diverse monitoring surveys have reported levels of
NSAIDs exceeding 1 μg/L in influent and effluents of WWTPs, while lower
concentrations have been found in surface waters [4, 10]. Among NSAIDs, paracetamol, diclofenac, and ibuprofen are the most detected therapeutics found in aquatic
ecosystems [4].
Paracetamol (PCM; N-(4-hydroxyphenyl)acetamide) is an analgesic and antipyretic agent. Although PCM does not own a proper anti-inflammatory action, it is
usually considered in the NSAID group by a toxicological point of view because of
its mode of action, similar to that of NSAIDs [11]. As PCM is considered a safe drug
at therapeutic doses, it can be purchased as an over-the-counter drug in most
countries. According to its extensive use, PCM is one of the most frequently detected
pharmaceuticals in surface waters, wastewaters, and drinking water. For instance,
Kolpin et al. [12] detected PCM in 24% of samples during a survey performed in
139 US streams, at a median concentration of 0.11 μg/L, with concentrations up to
10 μg/L. The median concentration of PCM measured in surface waters worldwide
was 0.055 Æ 0.051 μg/L [13, 14], while in wastewaters PCM was detected at a
median concentration of 48 Æ 75 μg/L [14, 15].
Diclofenac (DCF; 2-[(2,6-dichlorophenyl)amino] phenylacetic acid) is a
phenylacetic acid NSAID used to reduce inflammation and pain associated with
arthritis, osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis
[16]. According to its huge over-the-counter sale, coupled with the great number
Adverse Effects Induced by Nonsteroidal Anti-inflammatory Drugs on Freshwater. . .
149
concentrations ranging from a few ng/L to few mg/L in wastewater, surface water,
and groundwater worldwide [4, 6]. Although the environmental concentrations
measured in aquatic ecosystems are often quite low, pharmaceuticals are designed
to be biologically active at low concentrations; for this reason pharmaceuticals
revealed in environment might represent a potential risk for chronically exposed,
non-target organisms [3, 5]. Considering the potential hazard of pharmaceuticals
towards ecosystems some international actions have been planned. For instance, the
European Union has included 17α-ethinylestradiol, 17β-estradiol, and diclofenac to
the list of the Water Framework Directive (2013/39/EU) as priority molecules to be
monitored in aquatic ecosystems.
Nonsteroidal anti-inflammatory drugs (NSAIDs) represent one of the most relevant therapeutic class found in the aquatic ecosystems. NSAIDs are largely used for
their analgesic, antipyretic, and anti-inflammatory properties to cure pain and
inflammation. They inhibit the synthesis and the release of prostaglandins from
arachidonic acid, acting as non-selective inhibitors of cyclooxygenase enzymes,
including both the cyclooxygenase-1 (COX-1) and the cyclooxygenase-2 (COX-2)
isoforms [7]. Different NSAIDs have been prescribed extensively throughout the
world. For instance, more than 70 million prescriptions are written each year in the
United States, while considering the over-the-counter use, more than 30 billion
NSAID doses are consumed annually in the United States alone [8]. Because of
the huge, continuative and increasing use, as well as their specific pharmacokinetic
properties, NSAIDs can reach detectable concentrations both in sewage and in
surface water [9], accounting for 15% of pharmaceuticals measured in aquatic
ecosystems worldwide [4]. Diverse monitoring surveys have reported levels of
NSAIDs exceeding 1 μg/L in influent and effluents of WWTPs, while lower
concentrations have been found in surface waters [4, 10]. Among NSAIDs, paracetamol, diclofenac, and ibuprofen are the most detected therapeutics found in aquatic
ecosystems [4].
Paracetamol (PCM; N-(4-hydroxyphenyl)acetamide) is an analgesic and antipyretic agent. Although PCM does not own a proper anti-inflammatory action, it is
usually considered in the NSAID group by a toxicological point of view because of
its mode of action, similar to that of NSAIDs [11]. As PCM is considered a safe drug
at therapeutic doses, it can be purchased as an over-the-counter drug in most
countries. According to its extensive use, PCM is one of the most frequently detected
pharmaceuticals in surface waters, wastewaters, and drinking water. For instance,
Kolpin et al. [12] detected PCM in 24% of samples during a survey performed in
139 US streams, at a median concentration of 0.11 μg/L, with concentrations up to
10 μg/L. The median concentration of PCM measured in surface waters worldwide
was 0.055 Æ 0.051 μg/L [13, 14], while in wastewaters PCM was detected at a
median concentration of 48 Æ 75 μg/L [14, 15].
Diclofenac (DCF; 2-[(2,6-dichlorophenyl)amino] phenylacetic acid) is a
phenylacetic acid NSAID used to reduce inflammation and pain associated with
arthritis, osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis
[16]. According to its huge over-the-counter sale, coupled with the great number
Adverse Effects Induced by Nonsteroidal Anti-inflammatory Drugs on Freshwater. . .
149