BIOCHEMODYNAMICS

The onlyway to properly characterize biological systems is by simultaneously addressing chemical

reactions, motion, and biological processes.Mass and energy exchanges are taking place constantly

within and between cells, and at every scale of an ecosystem or a human population. Thus,

biochemodynamics addresses energy and matter as they move (dynamics), change (chemical

transformation), and cycle through organisms (biology).Asingle chemical or organismundergoes

biochemodynamics, from its release to its environmental fate (see Figure 1.1).

Since biotechnologies apply the principles of science, the only way to assess them properly is

by considering them biochemodynamically. Recently, the environmental community has

become increasingly proficient in using biomonitoring to assess ecosystem condition or to

determine pathways that have led to xenobiotic body burdens in humans. This has come to be

known as exposure reconstruction. In other words, by analyzing concentrations of substances

in tissue, the route that led to these concentrations can retrace the pathways, such as those in

Figure 1.1.

Reconstruction of body burden in an organism that follows the release of a substance to the

environment is an example of the biochemodynamic approach. To date, the use of biomonitoring

data for environmental assessment has been limited to relatively straightforward exposure scenarios, such as those involving inert and persistent chemicals with relatively long

biological half-lives and well-defined sources and pathways of exposure (e.g. the metal lead

[p3b] that is inhaled or ingested). More complex scenarios, including multiple chemical,

multiple route of entry to the body and multiple pathway exposures, will need to complement

biological information with large amounts of chemical and physical data (e.g. multimedia

dynamics of the chemical). Table 1.1 provides examples of available population biomarker

databases that can complement biomonitoring data.

Assessing biological doses and their effects using exposure measurements constitutes

a ‘‘forward’’ analytical approach, whereas estimating or reconstructing exposures from

biomarkers invokes an ‘‘inverse’’ methodology. The forward analysis can be accomplished

through the direct application of exposure, toxicokinetic, and toxicodynamic models

(discussed in Chapter 2), which can be either empirical or mechanistic (i.e. biologically

based). Reconstruction requires application of both numerical model inversion techniques

and toxicokinetic and/or toxicodynamic models. Physical, chemical, and biological information

must be merged into biochemodynamic information to underpin a systematic,

environmental assessment.

Physiologically based toxicokinetic (PBTK) and biologically based dose-response (BBDR)

models combined with numerical inversion techniques and optimization methods form

a biochemodynamic framework to support environmental risk assessment (see Figure 1.2).

The inversion approach contrasts with so-called ‘‘brute-force sampling,’’ wherein possible

factors as evaluated one-by-one. The biochemodynamic approach calls for a systematic evaluation

of available methods and computational tools that can be used to ‘‘merge’’ existing

forward models and biomarker data >.

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