IEAM Journal Spotlight: Tissue Residue Approach—Current Practice and Potential
Nancy Musgrove and John Toll, SETAC Globe Editors
Coming in the January 2011 issue of SETAC’s Integrated Environmental Assessment and Management is a series of six review articles on theory, practice, interpretation, limitations and advancements in the tissue residue approach (TRA) for assessing toxicity to aquatic organisms. These reviews are the result of a June 2007 Pellston Workshop, the purpose of which was to 1) review the science behind using TRA to develop dose metrics for assessing toxic responses, and 2) develop a coherent TRA application framework. The Globe’s editors have previewed these papers with the intent of spotlighting the upcoming IEAM and the recent Pellston workshop, and offer the following brief synopsis of what we found.
McCarty et al. provide a brief history of the TRA approach and the technical background for organic chemicals and metals in “Advancing environmental toxicology through chemical dosimetry: external exposures versus tissue residues.” They argue that although the toxicity of both organic and inorganic chemicals can be explained in tissue residue terms, the relationship between external exposure concentrations, body/tissues dose surrogates, and the effective internal dose at the site(s) of toxic action tends to be more complex for metals. They examine various issues and current limitations related to research and regulatory applications and make the case that TRA should be an integral component of future efforts to generate, understand, and utilize toxicity testing data, both in the laboratory and in the field.
Escher et al. talk about TRA’s mechanistic basis in “The crucial role of mechanisms and modes of toxic action for understanding tissue residue toxicity and internal effect concentrations of organic chemicals.” They argue that whole-body or organ concentrations (residues) can be better metrics for describing toxicity to aquatic organisms than the typically used external media concentrations, but that total internal concentrations still are only useful as dose-metrics to the extent that they provide a surrogate for the concentration or dose at the target site (the biologically effective dose). They explain that depending on the mechanism of toxicity, even the concentration at the target site might not be a sufficient descriptor of toxicity, and explain why.
Adams et al. evaluate the use of metal tissue residues for predicting effects in aquatic organisms in “Utility of tissue residues for predicting effects of metals on aquatic organisms.” Their evaluation includes consideration of different conceptual models, including a relatively new conceptual model in which metal tissue concentrations from metal-accumulating, but relatively insensitive invertebrates could be used to predict effects in metal sensitive taxa that typically don’t significantly accumulate metals. They present several case studies on how tissue residues might be applied for metals, assessing the strengths and weaknesses of different approaches. The authors argue that the use of the TRA for metals other than organometals has not led to the development of a generalized approach, as is the case for organic substances. They talk about species-specific and site-specific approaches that have been developed for one or more metals (e.g., nickel). The use of gill tissue residues within the biotic ligand model (BLM) as a successful TRA application is also discussed. They address the diverse array of homeostatic mechanisms in aquatic organisms, and why whole body (and often specific organ) measurements do not lead to a defensible position regarding risk. A rationale is presented for pursuing species-specific and site-specific approaches for metals.
McElroy et al. review TRA for toxicity assessment as it applies to organic chemicals and some organometallic compounds (tin, mercury, and lead) in aquatic organisms in “A review of the tissue residue approach for organic and organometallic compounds in aquatic organisms.” They emphasize evaluating key factors influencing interpretation of critical body residue (CBR) thresholds: including data quality issues, lipid dynamics, choice of endpoints, processes that alter toxicokinetics and toxicodynamics, phototoxicity, species and life-stage specific sensitivities, and biotransformation. The vast majority of data available on TRA is derived from laboratory studies of acute lethal responses to organic toxicants exhibiting baseline toxicity. Applications of the TRA to various baseline toxicants as well as substances with specific modes of action via receptor-mediated processes (e.g., chlorinated aromatic hydrocarbons, pesticides, and organometals) are discussed, along with application of TRA concepts in field assessments of tissue residues. Factors limiting the use TRA for organic and organometallics compounds are addressed, including influence of biotransformation, contaminant lipid interactions, time dependency of CBRs, receptor-mediated toxicity, and the need for additional residue-effects data on sublethal endpoints, early life stages, and a wider range of legacy and emergent contaminants.
Dyer et al. review the literature related to TRA for chemical mixtures and recommend a practical, tiered approach that can be implemented in regulatory or risk assessment applications. As with the toxicity of individual chemicals, there are a number of significant advantages to addressing mixture toxicity via TRA. These are addressed. The authors discuss the theoretical basis for, experimental data, and field-based validation to support the use of the TRA for mixtures. They recommend a framework for addressing the toxicology of mixtures that integrates the TRA and mixture toxicology.
In the last paper in this series, “Application of the tissue residue approach in ecological risk assessment,” Sappington et al. critically review the use of TRA in ecological risk assessment and environmental criteria development. They summarize TRA applications for bioaccumulative organic chemicals, TBT, and in situ bioassays using bivalve molluscs. The authors present a framework for integrating TRA into ecological assessments along with traditional, exposure concentration-based assessment approaches. They identify the important factors to consider when deciding whether to use TRA in specific situations, and make the case that rather than supplanting exposure concentration-based toxicity assessments, the TRA can be highly effective for evaluating and reducing uncertainty when used in a complementary manner (e.g., when evaluating multiple lines of evidence in field studies). They discuss extrapolating residue-based toxicity data across species, tissues, and exposure durations to address limitations with the available tissue residue response data.
Tissue residues have been used as dose metrics in environmental toxicology for over 100 years, but water and dietary concentrations have been the predominant metrics for establishing exposure and effect, in part due to toxicology’s medical roots and the limitations of testing and analytical technologies during the development of this field. However, relationships between media concentrations and actual effects can vary widely for a given substance depending on the species, their sensitivity or degree of site-specific acclimation, lifestage, exposure medium (e.g., water, sediment) and pathways (dermal contact, ingestion), chemical type and form, exposure duration, and toxicodynamic factors. As a result, lethal concentrations in environmental media (e.g., aqueous LC50s) can vary by orders of magnitude, complicating the interpretation of these data. Toxicity, when measured as a tissue residue, is often found to occur over a much narrower range given the same confounding factors. As such, TRA might offer a less variable metric for assessing deleterious effects as compared to external media-based toxicity assessments. Tissue residues integrate exposure pathways, incorporate effects of spatial and temporal variation in exposure and assist in evaluating chemical bioavailability, but they are still surrogates for the actual dose at the site of effect within an organism.
Keep your eyes open for this upcoming issue or if you can’t wait, go to the IEAM journal page and click on Accepted Articles!
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