Approaching a closer surrogate for the biologically effective dose with subcellular partitioning-based toxicokinetic models

Critical Reviews in Environmental Science and Technology, vol. 53, pp. 1103–1125

Abstract

A general concept in risk assessment is that a threshold of exposure exists above which adverse effects are initiated. Toxicity is related to the target-site concentration or the biologically active dose. Although it is often a huge challenge to measure the specific dose metric of metal toxicity, significant progress has been obtained to approach closer to the target-site concentration. Such developments are reviewed in the present study. In addition, a general framework to simulate the subcellular metal partitioning, which is supposed to account for the internal metal sequestration, is developed and applied to various metals. The framework allows for delineating mechanisms of internal metal sequestration. Moreover, the specificity in these mechanisms, which varies among metals, species, and exposure conditions, might explain the complicated relationship between the internal concentration and metal toxicity. Attention should be paid to the data requirements as the high number of unknown parameters might be accompanied by potential uncertainties. In addition, future efforts should focus on linking the concentration of metals in sensitive fractions and toxicological effects.

Authors 4

1. T.T. Yen Le corresponding

   University of Duisburg-Essen

   Affiliation as printed

   Department of Aquatic Ecology, University of Duisburg-Essen

   Department of Aquatic Ecology, University of Duisburg-Essen, Essen, Germany

2. Olivier Geffard

   Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement · Fonctionnement des hydrosystèmes

   Affiliation as printed

   Laboratoire d‘écotoxicologie, INRAE, UR RiverLy

   Laboratoire d‘écotoxicologie, INRAE, UR RiverLy, Villeurbanne, France

3. Alain Geffard

   Stress Environnementaux et Biosurveillance des Milieux Aquatiques · Université de Reims Champagne-Ardenne

   Affiliation as printed

   Laboratoire d’Eco-Toxicologie, Université Reims Champagne Ardenne, UMR-I 02 SEBIO, UFR Sciences Exactes et Naturelles

   Laboratoire d’Eco-Toxicologie, Université Reims Champagne Ardenne, UMR-I 02 SEBIO, UFR Sciences Exactes et Naturelles, Reims, France

4. Willie J.G.M. Peijnenburg Aachen Institute for Environmental Sciences (CML)

   Leiden University · National Institute for Public Health and the Environment

   Affiliation as printed

   Center for Safety of Substances and Products, National Institute for Public Health and the Environment

   Institute for Environmental Sciences, Leiden University

   RIVM - National Institute for Public Health and the Environment [Bilthoven] (Antonie van Leeuwenhoeklaan 9, 3721 MA, Bilthoven / PO Box 1, 3720 BA Bilthoven - Netherlands)

   Universiteit Leiden = Leiden University (Leiden University | 2300 RA Leiden The Netherlands - Netherlands)