Time will be needed ...

Abstract.

Understanding the toxicity of chemicals to organisms requires considering the molecular mechanisms involved as well as the relationships between exposure concentration and toxic effects with time. Our current knowledge about such relationships is mainly explained from a toxicodynamic and toxicokinetic perspective. This paper re-introduces an old approach that takes into account the biochemical mode of action and their resulting biological effects over time of exposure. Empirical evidence demonstrates that the Druckrey–Küpfmüller toxicity model, which was validated for chemical carcinogens in the early1960s, is also applicable to a wide range of toxic compounds in ecotoxicology. According to this model, the character of a poison is primarily determined by the reversibility of critical receptor binding. Chemicals showing irreversible or slowly reversible binding to specific receptors will produce cumulative effects with time of exposure, and whenever the effects are also irreversible (e.g. death) they are reinforced overtime; these chemicals have time-cumulative toxicity. Compounds having non-specific receptor binding, or involving slowly reversible binding to some receptors that do not contribute to toxicity, may also be time-dependent; however, their effects depend primarily on the exposure concentration, with time playing a minor role. Consequently, the mechanism of toxic action has important implications for risk assessment. Traditional risk approaches cannot predict the impacts of toxicants with time-cumulative toxicity in the environment. New assessment procedures are needed to evaluate the risk that the latter chemicals pose on humans and the environment. An example is shown to explain how the risk of time-dependent toxicants is underestimated when using current risk assessment protocols.

Henk A. Tennekes, Experimental Toxicology Services (ETS) Nederland BV, Frankensteeg 4, 7201 KN Zutphen, The Netherlands Centre for Ecotoxicology, 
Francisco Sánchez-Bayoba, University of Technology Sydney, C/480 Weeroona Road, Lidcombe, NSW 2141, Australia.

Elsevier Ireland Ltd. All rights reserved.

Article history: Received 19 February 2013 - Received in revised form 9 April 2013 - Accepted 10 April 2013.


Ghislain De Roeck,
Belgium.

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