Understanding bioavailability requires information from various disciplines. Knowledge of bioavailability is critical for understanding the fate and transport of contaminants in diverse environments, the extent and rate at which contaminants can be degraded by microorganisms, the rate and extent of uptake of contaminants by humans and wildlife, and the availability of the assimilated compounds and ions to organs and tissues. Bioavailability of chemicals is impacted by many factors of both the environment in which the chemical exists and within the target organisms. There are many gaps in our knowledge of how these factors interact and how they impact human health and exposure risk.
This meeting of a small group of academicians, regulatory personnel and practicing professionals discussed three issues: identification of concepts common to different disciplines, examination of the relationships between bioavailability and exposure, and use of data-mapping tools to assess the relationships between exposure and health.
The speakers considered the dimensions of bioavailability in different problem areas, issues related to common concepts and terms, and defining research questions and ways to use bioavailability in risk and exposure assessment.
Several issues came up repeatedly and about which there seemed to be general agreement. These include:
The absence of a good approach for relating exposure to effects
The need for better methods for measurement of exposure and effects
The lack of adequate knowledge of environmental properties controlling exposure
The inadequate understanding of differences among species and among compounds and ions
Often, methods are inadequate to properly address these issues
A particular limitation to developing an understanding has been the absence of multi- and interdisciplinary groups that are critical to assessing issues and approaches to bioavailability
Although bioavailability is only one part of assessments of exposure and risk, it is clearly an indispensable part.
The questions and issues posed in the individual presentations and ensuing discussions included the following.
The problem of terminology: Toxicologists use the term bioaccessibility in reference to uptake from an organism's environment. Environmental scientists designate this uptake by the word bioavailability. It was agreed that specialists should define their terms and not become embroiled in semantic arguments.
The need for future opportunities to bring toxicologists and environmental scientists together because their ultimate goals are similar and often identical. Many of the critical issues can only be addressed by combining the skills of these disparate groups.
The need to develop priorities on subjects for future research.
The need for multi- and interdisciplinary teams to address the multitude of issues in human and animal toxicology and in environmental sciences relative to bioavailability and bioaccessibility.
The critical role of communication of information to practitioners, including those concerned with regulatory issues, human and animal health, risk assessment, environmental remediation and others.
Establishing what bioavailability information is needed to help make regulatory and management decisions.
The importance of field and laboratory validation of methods and models.
A rationale for deciding when to use model systems rather than actual measurements.
The need for reliable information on both metals and organic compounds.
Metabolism in humans and animals, as well as biological and abiotic processes in natural and polluted environments create breakdown products, metabolites and conjugates. Often these by-products have dissimilar bioavailabilities and effects and can be distributed and transported in different ways, therefore it is essential to establish the identities and behaviors of these products.
The focus in the past has been almost entirely on the bioavailability of single compounds, but consideration should be given to the bioavailability of mixtures of compounds and ions.
Further attention should be given to the proper use of GIS as a tool in bioavailability assessments.
Because of the few species that have been tested under comparable experimental conditions, it is difficult to deduce systematic patterns of chemicals and response from toxicological studies.
The juvenile swine model is often considered as the "gold standard," in toxicity assessments for some chemicals, but it is expensive and time-consuming. How well is the model verified and can a less expensive and less time-consuming model be developed?
How well do pharmacokinetic and other drug models apply to bioavailability of compounds and ions from contaminated environments? Are there better models now and can better ones be developed?
Very large cohort studies with large samples and appropriate controls may be needed for some evaluations, but are very expensive and required complex teams of scientists to develop and properly conduct.
Few of the many existing biomarkers have been evaluated for their relationship to the development of human disease.
Existing models are based on a single exposure scenario of time and environmental conditions, but bioavailability is greatly affected by season and changes in environmental conditions. Can we develop better models or incorporate environmental variability into existing models?
The role of human and animal oral bioavailability to tissue concentration and subsequent response should be evaluated further.
Information is needed on possible differences in bioavailability of metals and organic compounds in contaminated environments to different age groups, including children.
Rapid, inexpensive methods are needed to assess dermal and gastrointestinal bioavailability from soil and from excavated sediments, especially in view of the large spatial heterogeneity and temporal variability in chemical concentration and the nature of chemical mixtures.
The bioavailabilities of compounds in soil and probably sediments differ appreciably, and it is important to understand the reasons for these differences and to be able to predict how different compounds will behave.
Because physical and chemical properties of contaminated soils and sediments are very different, it is critical to establish the role of these properties in determining the bioavailability of metals and organic compounds. This will require input from specialists in soil and sediment chemistry, physics and microbiology.
The bioavailability of many chemicals from soils declines with time, often markedly so. Therefore, it is important to understand why such a decline occurs and how to predict future bioavailable concentrations.
A review should be made of the large literature on bioavailability of inorganic ions to plants to determine which information may be relevant to bioavailability assessments for humans and wildlife, particularly because that availability is controlled by soil properties that may be of general biological significance.
The interaction of environmental, biomedical, and regulatory scientists revealed that all face similar questions and many of the same experimental problems. In the continuum between the existence of chemicals in the environment and the development of specific diseases in humans, there are many gaps in knowledge. In order to protect the health of the public and clean up contamination in the environment, it is necessary to address those gaps. Dialogue between the different disciplines involved in this meeting was a first and essential step in bridging those gaps.
Prepared by Martin Alexander and Frederic Pfaender