Pharmaceuticals in the environment

Fate in the environment

The presence of pharmaceuticals in the environment has been discovered worldwide, with high concentrations in regions with limited sanitation, and lower concentrations in regions with sewage treatment facilities (Wilkinson et al., 2022). 

Once active pharmaceutical ingredients (APIs) and their metabolites enter the water system, they do not always stay there. The fate of a chemical in the environment is determined by mobility and degradation, i.e. where it goes and in what form (van de Meent and Matthies, 2019). Many APIs and their metabolites will be (further) degraded into 'transformation products', but this may take some time and may not always be complete, resulting in persistent chemicals. Depending on their physicochemical characteristics, residues of APIs, metabolites and transformation products may sorb to sediments or soils or leach into groundwater. Thus, degradation and sorption processes determine how these compounds will be distributed over various environmental compartments.

Degradation and persistence

In the environment, degradation of APIs leads to transformation products. The molecular structures of metabolites and transformation products and the way they behave in the environment (and associated risks) may be similar, the only difference is where and how these compounds are formed (in humans versus the environment). When a compound is not degraded, it is persistent in the environment.

Transformation of organic chemicals in the environment can occur in different ways:

• Chemical reactions e.g., hydrolysis, oxidation, and photochemical reactions.

• Biochemical degradation happens due to microbial activity.

In many cases, chemicals will be removed by combinations of these different processes and it is sometimes difficult to identify the contributions of the different mechanisms. Indeed, combinations of different mechanisms are sometimes important, for example in cases where microbial activity is responsible for creating conditions that favour chemical reactions (van de Meent and Matthies, 2019). 

Such transformation processess can change (1) the biological activity and thus toxicity of a molecule; (2) physicochemical properties and thus its fate in environmental compartments or its bioavailability. Both metabolites and transformation products may still have some biological activity. If they are more stable than the parent compound and thus exist in higher concentrations, the risks due to metabolites and/or transformation products may be greater than those of the parent compound.

Because of continuous emissions in waste water, even when degradation happens relatively fast, the concentration of APIs and/or their metabolites may not decrease and are always present in the environment. Only for compounds that are fully mineralised (converted to carbon dioxide, nitrates, sulphates, etc.) this is not the case. 

Sorption

The fate of pharmaceutical residues, metabolites and transformation products may be the aquatic environment (where it is emitted), but alternatively the bottom layer in surface water (sediment), soils or groundwater. This depends on the extent to which compounds sorb to sediments and soils. This sorption behaviour is is governed by a few basic properties  (van de Meent and Matthies, 2019): 

• Hydrophobicity (the affinity of a substance towards water) or lipophilicity (the tendency of a substance to dissolve in lipids) is mainly governed by molecular size and polarity. Small and polar molecules interact with water, for example by hydrogen bonding. Larger molecules with weak or no hydrogen bonding disrupt the hydrogen bond network already present in water. A simple measure for the hydrophobicity of chemicals, originating from pharmacology, is the octanol-water partition coefficient, abbreviated as KOW. This is the ratio of the concentration of a chemical in n-octanol and in water, after establishment of an equilibrium between the two phases under laboratory conditions.

• Volatility (tendency of a substance to vapourise) also effects the partition of substances between water and air.

• Whether or not a compound is ionised, as that changes its ability to dissolve in water. 

Sorption of chemicals determines its fate in the environment in a number of ways:

• Sorbed chemicals are less biologically available (low exposure). This influences risk but also the extent to which microorganisms can access the molecule for biodegradation.

• Sorbed chemicals are bound to sediments or soils and will not be transported across water systems in the same way as dissolved chemicals do, which are much more mobile and may end up in groundwater.