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Organisms are able to control metal concentrations in certain tissues of their body to minimize damage of reactive forms of essential and nonessential metals and to control selective utilization of essential metals. These physiological aspects of organisms are not accounted for when assessing the risk of metals in the environment. The Critical Body Residue (CBR) approach relates toxicity to bioaccumulation and biomagnification and might at first sight provide a more accurate estimation of effects than the external concentration. When expressing CBRs on total internal concentrations, the capacity of organisms to sequester metals in forms that are not biologically reactive is neglected. The predictability of toxic effects will increase when knowledge on metal compartmentalization within the organisms' body is taken into account. Insight in metal compartmentalization sheds light on the different accumulation strategies organisms can follow upon metal exposure. Using a fractionation procedure to isolate metal-rich granules and tissue fragments from intracellular and cytosolic fractions, the internal compartmentalization of metals can be approximated. In this paper, current knowledge regarding metal compartmentalization in organisms is summarized, and metal fractions are identified that are indicators of toxicity. Guidance is provided on future improvement of models, such as the Biotic Ligand Model (BLM), for risk assessment of metal stress to biota.

(93) In order to finalise the procedure in due time, the Agency should submit its opinions on the suggested action and its impact on the basis of a draft opinion prepared by a rapporteur.(94) In order to speed up the procedure for restrictions, the Commission should prepare its draft amendment within a specific time limit of receiving the Agency's opinions.(95) The Agency should be central to ensuring that chemicals legislation and the decision-making processes and scientific basis underlying it have credibility with all stakeholders and the public. The Agency should also play a pivotal role in coordinating communication around this Regulation and in its implementation. The confidence in the Agency of the Community institutions, the Member States, the general public and interested