Keywords Anti-inflammatories, Antipyretic, Bioaccumulation, Ecotoxicity,
Micropollutants
1 Introduction
Pharmaceutical products are present in the environment as a result of patient use,
production, and formulation of the drug and improper disposal [1]. Based on this
knowledge, the European Medicines Agency (EMA) issued a Guide for Environmental Risk Assessment (ERA) of medicines for human use in 2006 [2]. This
guideline consists of two phases. In Phase I, the predicted environmental concentration (PEC) for surface water is calculated, and the octanol-water partition coefficient (K ow ) is measured. If the PEC is above 0.01 μg L
À1 , a Phase II evaluation is
performed; if logK ow 4.5, persistence, bioaccumulation potential, and toxicity should
be evaluated. Pharmaceuticals that are known to have toxic activity in concentrations
below 0.01 μg L
À1 must also enter Phase II, following a personalized risk assessment
strategy that addresses their specific mechanism of action. Phase II is divided into
two levels (A and B). Level A involves a basic set of aquatic toxicity and target tests
to determine the predicted no-effect concentration (PNEC) for three trophic levels
(algae, daphnia, and fish). Level B consists of an extended evaluation that uses
refined values for PEC and PNEC calculations. At this stage, both an analysis of the
destination and effect studies can be performed. The pharmaceutical product is
evaluated by generating a risk quotient (RQ), evaluating the relationship between
the PEC and the PNEC; when the ratio is less than 1, no risk is expected from the
pharmaceutical environment for the aquatic environment.
In recent years, the level of health care is increasing, so various pharmaceutical
products are frequently used to cure diseases such as muscle pain, headache, and
some inflammatory conditions. Nonsteroidal anti-inflammatory drugs (NSAIDs) are
generally used to cure any type of pain. NSAIDs are mainly derivatives of carboxylic
acid that act by inhibiting the synthesis of prostaglandins produced by the cyclooxygenase enzyme that is present in various tissues and that is responsible for the
mediation of various physiological signals. Among the most consumed NSAIDs are
diclofenac, naproxen, ketoprofen, ibuprofen acetylsalicylic acid, and paracetamol
[3]. Among the main reasons that this pharmacological class is among the most
consumed worldwide is that its sale does not require a prescription; they are
inexpensive and usually have fewer side effects [4].
In particular, diclofenac has been used as a NSAID for human health purposes
since the 1970s, and in some countries, it has been used as an all-purpose veterinary
medicine for domestic livestock. Regarding human health purposes, the global
annual consumption averaged 1,443 Æ 58 t [5]. It is due to this that it has been
habitually detected in the environment and that the study of the risk that it could have
when being in contact with the organisms becomes relevant. Table 1 presents some
of the studies that have been carried out regarding this pharmaceutical.
322
J. D. Cardoso-Vera et al.
Micropollutants
1 Introduction
Pharmaceutical products are present in the environment as a result of patient use,
production, and formulation of the drug and improper disposal [1]. Based on this
knowledge, the European Medicines Agency (EMA) issued a Guide for Environmental Risk Assessment (ERA) of medicines for human use in 2006 [2]. This
guideline consists of two phases. In Phase I, the predicted environmental concentration (PEC) for surface water is calculated, and the octanol-water partition coefficient (K ow ) is measured. If the PEC is above 0.01 μg L
À1 , a Phase II evaluation is
performed; if logK ow 4.5, persistence, bioaccumulation potential, and toxicity should
be evaluated. Pharmaceuticals that are known to have toxic activity in concentrations
below 0.01 μg L
À1 must also enter Phase II, following a personalized risk assessment
strategy that addresses their specific mechanism of action. Phase II is divided into
two levels (A and B). Level A involves a basic set of aquatic toxicity and target tests
to determine the predicted no-effect concentration (PNEC) for three trophic levels
(algae, daphnia, and fish). Level B consists of an extended evaluation that uses
refined values for PEC and PNEC calculations. At this stage, both an analysis of the
destination and effect studies can be performed. The pharmaceutical product is
evaluated by generating a risk quotient (RQ), evaluating the relationship between
the PEC and the PNEC; when the ratio is less than 1, no risk is expected from the
pharmaceutical environment for the aquatic environment.
In recent years, the level of health care is increasing, so various pharmaceutical
products are frequently used to cure diseases such as muscle pain, headache, and
some inflammatory conditions. Nonsteroidal anti-inflammatory drugs (NSAIDs) are
generally used to cure any type of pain. NSAIDs are mainly derivatives of carboxylic
acid that act by inhibiting the synthesis of prostaglandins produced by the cyclooxygenase enzyme that is present in various tissues and that is responsible for the
mediation of various physiological signals. Among the most consumed NSAIDs are
diclofenac, naproxen, ketoprofen, ibuprofen acetylsalicylic acid, and paracetamol
[3]. Among the main reasons that this pharmacological class is among the most
consumed worldwide is that its sale does not require a prescription; they are
inexpensive and usually have fewer side effects [4].
In particular, diclofenac has been used as a NSAID for human health purposes
since the 1970s, and in some countries, it has been used as an all-purpose veterinary
medicine for domestic livestock. Regarding human health purposes, the global
annual consumption averaged 1,443 Æ 58 t [5]. It is due to this that it has been
habitually detected in the environment and that the study of the risk that it could have
when being in contact with the organisms becomes relevant. Table 1 presents some
of the studies that have been carried out regarding this pharmaceutical.
322
J. D. Cardoso-Vera et al.