## 3.6.1. Definitions

Authors: Martina Vijver

Reviewer: Kees van Gestel, Ravi Naidu

Learning objectives:

You should be able to:

- understand that bioavailability consists of three principle processes.
- understand that bioavailability is a dynamic concept.
- understand why bioavailability is important to explain uptake and effects, essential for a proper risk assessment of chemicals.

Keywords: Chemical availability, actual and potential uptake, toxico-kinetics, toxico-dynamics.

Introduction:

Although many environmental chemists, toxicologists, and engineers claim to know what bioavailability means, the term eludes a consensus definition. Bioavailability may be defined as that fraction of chemical present in the environment that is or may become available for biological uptake by passage across cell membranes.

Figure 1. Bioavailability relates to a series of processes, ranging from processes external of organisms, towards internal tissues, and fully internal to the biological response site. Redrawn from Ortega-Calvo et al. (2015) by Wilma IJzerman.

Bioavailability generally is approached from a process-oriented point of view within a toxicological framework, which is applicable to all types of chemicals (Figure 1).

The first process is chemical availability which can be defined as the fraction of the total concentration of chemicals present in an environmental compartment that contributes to the exposure of an organism. The total concentration in an environmental compartment is not necessarily involved in the exposure, as a smaller or larger fraction of the chemical may be bound to organic or inorganic components of the environment. Organic matter and clay particles, for instance, are important in binding chemicals (see section on Soil), while also the presence of cations and pH are important factors modifying the partitioning of chemicals between different environmental phases (see section on Metal speciation).

The second process is the actual or potential uptake, described as the toxicokinetics of a substance which reflects the development with time of its concentration on, and in, the organism (see section on Bioconcentration and kinetics modelling).

The third process describes the internal distribution of the substance leading to its interaction(s) at the cellular site of toxicity activation. This is sometimes referred to as toxico-availability and also includes the biochemical and physiological processes resulting from the effects of the chemical at the site of action.

Details on the bioavailability concept described above as well as how the physico-chemical interactions influencing each process are described in the sections on Metal speciation and Bioconcentration and kinetics modelling.

Figure 2. Bioavailability relates to a series of time frames, particularly in external processes (according to Ortega-Calvo et al. 2015).

Kinetics are involved in all three basic processes. The timeframe can vary from very brief (less than seconds) to very long in the order of hundreds of years. Figure 2 shows that some fractions of pollutants are present in soil or sediment, but may never contribute to the transport of chemicals that could reach the internal site during an organism’s lifespan. The fractions with different desorption kinetics may relate to different experimental techniques to determine the relevant bioavailability metric.

Box 1: Illustration of how bioavailability influences our human fitness Iron deficiency occurs when a body has not enough iron to supply its needs. Iron is present in all cells of the human body and has several vital functions. It is a key component of the hemoglobin protein, carrying oxygen to the tissues from the lungs. Iron also plays an important role in oxidation/reduction reactions, which are crucial for the functioning of the cytochrome P450 enzymes that are responsible for the biotransformation of endogenic as well as xenobiotic chemicals. Iron deficiency therefore can interfere with these vital functions, leading to a lack of energy (feeling tired) and eventually to malfunctioning of muscles and the brain. In case of iron deficiency, the medical doctor will prescribe Fe-supplements and iron-rich food such as red meat and green leafy vegetables like spinach. Although this will lead to a higher intake of iron (after all exposure is higher), it does not necessarily lead to a higher uptake as here bioavailability becomes important. It is advised to avoid drinking milk or caffeinated drinks together with eating iron-rich products or supplements because both drinks will prevent the absorption of iron in the intestinal tract. Calcium ions abundant in milk will compete with iron ions for the same uptake sites, so excess calcium will reduce iron uptake. Carbonates and caffeine molecules, but also phytate (inositol polyphosphate) present in vegetables, will strongly bind the iron, also reducing its availability for uptake.

Figure 3. Bioavailability correction to estimate the HC5 copper concentration in relation to properties like dissolved organic carbon content and pH (Table 1) in order to estimate its risk in different water types (according to Vijver et al. 2008), in comparison to the 1.5 µg/L total dissolved Cu in surface waters as the current generic Dutch standard (horizontal line). Redrawn from Vijver et al. (2008) by Wilma Ijzerman

Bioavailability used in Risk Assessment

For regulatory purposes, it is necessary to use a straightforward approach to assess and prioritize contaminated sites based on their risk to human and environmental health. The bioavailability concept offers a scientific underpinned concept to be used in risk assessment. Examples for inorganic contaminants are the derived 2nd tier models such as the Biotic Ligand Models, while for organic chemicals the Equilibrium Partitioning (EqP) concept (see Box 2 in the section on Sorption) is applied.

A quantitative example is given for copper in different water types in Figure 3 and Table 1, in which water chemistry is explicitly accounted for to enable estimating the available copper concentration. The current Dutch generic quality target for surface waters is 1.5 µg/L total dissolved copper. The bioavailability-corrected risk limits (HC5) for different water types, in most cases, exceeded this generic quality target.

Table 1. Bioavailability adjusted Copper 5% Hazardous Concentration (HC5, potentially affecting <5% of relevant species) for different water types.

Water type description | no. | DOC (mg/L) | pH | Average HC5 (µg/L)
Large rivers | 1 | 3.1 ± 0.9 | 7.7 ± 0.2 | 9.6 ± 2.9
Canals, lakes | 2 | 8.4 ± 4.4 | 8.1 ± 0.4 | 35.0 ± 17.9
Streams, brooks | 3 | 18.2 ± 4.3 | 7.4 ± 0.1 | 73.6 ± 18.9
Ditches | 4 | 27.5 ± 12.2 | 6.9 ± 0.8 | 64.1 ± 34.5
Sandy springs | 5 | 2.2 ± 1.0 | 6.7 ± 0.1 | 7.2 ± 3.1

When the calculated HC5 value is lower, this means that the bioavailability of copper is higher and hence at the same total copper concentration in water the risk is higher. The bioavailability-corrected HC5s for Cu differ significantly among water types. The lowest HC5 values were found for sandy springs (water type V) and large rivers (water type I), which appear to be sensitive water bodies. These differences can be explained from partitioning processes (chemical availability) and competition processes (the toxicokinetics step) on which the BLMs are based. Streams and brooks (water type III) have rather high total copper concentrations without any adverse effects, which can be attributed to the protective effect of relatively high dissolved organic carbon (DOC) concentrations and the neutral to basic pH causing a high binding of Cu to the DOC.

For risk managers, this water type specific risk approach can help to identify the priority in cleanup activities among sites having elevated copper concentrations. It remains possible that, for extreme environmental situations (e.g., extreme droughts and low water discharges or extreme rain fall and high runoff), combinations of the water chemistry parameters may result in calculated HC5 values that are even lower than the calculated average values. For the latter (important) reason, the generic quality target is more strict.

References

Hamelink, J., Landrum, P.F., Bergman, H., Benson, W.H. (1994) Bioavailability: physical, chemical, and biological interactions, CRC Press.

Ortega-Calvo, J.J., Harmsen, J., Parsons, J.R., Semple, K.T., Aitken, M.D., Ajao, C., Eadsforth, C., Galay-Burgos, M., Naidu, R., Oliver, R., Peijnenburg, W.J.G.M., Römbke, J., Streck, G., Versonnen, B. (2015) From bioavailability science to regulation of organic chemicals. Environmental Science and Technology 49, 10255−10264.

Vijver, M.G., de Koning, A., Peijnenburg, W.J.G.M. (2008) Uncertainty of water type-specific hazardous copper concentrations derived with biotic ligand models. Environmental Toxicology and Chemistry 27, 2311-2319.