Advancing environmental toxicology through chemical dosimetry: External exposures versus tissue residues

Abstract

The tissue residue dose concept has been used, although in a limited manner, in environmental toxicology for more than 100 y. This review outlines the history of this approach and the technical background for organic chemicals and metals. Although the toxicity of both can be explained in tissue residue terms, the relationship between external exposure concentration, body and/or tissues dose surrogates, and the effective internal dose at the sites of toxic action tends to be more complex for metals. Various issues and current limitations related to research and regulatory applications are also examined. It is clear that the tissue residue approach (TRA) should be an integral component in future efforts to enhance the generation, understanding, and utility of toxicity testing data, both in the laboratory and in the field. To accomplish these goals, several key areas need to be addressed: 1) development of a risk-based interpretive framework linking toxicology and ecology at multiple levels of biological organization and incorporating organism-based dose metrics; 2) a broadly applicable, generally accepted classification scheme for modes/mechanisms of toxic action with explicit consideration of residue information to improve both single chemical and mixture toxicity data interpretation and regulatory risk assessment; 3) toxicity testing protocols updated to ensure collection of adequate residue information, along with toxicokinetics and toxicodynamics information, based on explicitly defined toxicological models accompanied by toxicological model validation; 4) continued development of residue-effect databases is needed ensure their ongoing utility; and 5) regulatory guidance incorporating residue-based testing and interpretation approaches, essential in various jurisdictions.

Determining potential adverse effects in marine fish exposed to pharmaceuticals and personal care products with the fish plasma model and whole-body tissue concentrations

“…Tissue concentrations are one important step closer in the progression from ambient exposure to concentrations in whole body, organs, and at the receptor. Using tissue concentrations as the dose metric generally provides an important reduction in variability compared to modeling toxicity from water exposure to compound concentrations at the site of the molecular initiating event (Meador et al 2008; McCarty et al 2011). As with any aquatic toxicity assay, it is assumed that the ambient exposure concentration is proportional to the tissue concentration, which is in turn proportional to the concentration at the receptor (McCarty et al 2011).…”

“…Using tissue concentrations as the dose metric generally provides an important reduction in variability compared to modeling toxicity from water exposure to compound concentrations at the site of the molecular initiating event (Meador et al 2008; McCarty et al 2011). As with any aquatic toxicity assay, it is assumed that the ambient exposure concentration is proportional to the tissue concentration, which is in turn proportional to the concentration at the receptor (McCarty et al 2011). This concept can be applied here and in this case we are using the fish plasma concentration as a surrogate for the internal concentration that can be related to human therapeutic concentrations as measured in plasma.…”

Reduced Life Expectancy Model for Effects of Long Term Exposure on Lethal Toxicity with Fish

“…Toxicity is a function of both exposure time period and concentration or dose [1–4]. Nevertheless most of the toxicological data are based on the quantitative relationship between concentration or dose and adverse effect without consideration of the exposure time period [5–7].…”

Processes, Assessment and Remediation of Contaminated Sediments

“…For those with higher variability, the use of tissue residues based on a species sensitivity distribution would be the most appropriate method for determining the critical body burden for protecting the most sensitive species (Steevens et al, 2005). The application of the TRA approach for the evaluation of effects elicited by non-polar organic compounds and organometallic compounds has been critically reviewed and its strengths and limitations discussed (Barron et al, 2002;Landrum and Meador, 2002;McElroy et al, 2011;McCarty et al, 2011). For metals, the application of whole-body residues as threshold criteria associated with effects does not lead to a defensible prediction of risk to the organism largely due to the existence of metal-and species-specific physiological mechanisms that facilitate acclimation to metal exposure .…”