Developing Oral Bioavailability Data for Health Risk Assessments

Rosalind A. Schoof, Ph.D.

Ramboll US Corporation, USA

rschoof@ramboll.com

Increasing numbers of countries include site-specific adjustments in health risk assessments to account for differing relative bioavailability (RBA) of chemicals in soil. This talk will describe how RBA is incorporated into health risk assessments and will provide an overview of the history of development of methods for testing metal RBA in soil. The early focus in the late 1980s was on use of animal models to test lead and arsenic RBA, followed soon after by the development of in vitro test systems.

While animal studies have generally been considered the more reliable predictor of RBA in humans, differences in physiology and anatomy among animal species limit the accuracy of these models in predicting behavior in humans. Further, variations in toxicokinetics and other factors result in the need to apply different study designs to different metals. In vivo methods used to assess the bioavailability of soil-borne chemicals are typically modified versions of methods used historically in biomedical research. These methods have been modified to address constraints associated with use of doses relevant to environmental concentrations, the need to reflect weathering behavior in soils over time, and the need to generate data applicable to human health risk assessments. Lead and arsenic provide examples of such differences with arsenic being rapidly excreted in the urine, while lead accumulates in bone and has a much longer half-life in the body. Due to these differences, animal methods to calculate RBA differ for lead and arsenic.

In contrast, a number of in vitro methods now in use have been validated by comparison with animal test results and are considered at least as reliable as animal studies. The prevailing methods in use in Europe, Canada, the United States and Australia will be described. Current in vitro methods for assessing lead and arsenic will be used to illustrate application of these models in risk assessment. Methods being applied to other metals will also be reviewed. While research and methods development effort has focused on evaluation of the relative bioavailability of lead and arsenic in soil, extension of these findings to other metals has been a subject of some debate. Factors that could affect applicable methods for a given metal include differences in toxicokinetics and toxic endpoints. Studies of the bioavailability of soil Cd, Cr, Ni and Hg will be described to illustrate a range of issues and approaches that are compared with approaches used for arsenic and lead. Recommendations for evaluation of other metals will be provided.

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