Time-dependent toxicity of neonicotinoids and other toxicants: Implications for a new approach to risk assessment

OMICS Publishing Group
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Journal Article
Journal of Environmental & Analytical Toxicology, 2011, 2011 (04), pp. 1 - 8
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A fundamental goal of toxicology is to determine safe levels of exposure to potentially poisonous substances for humans and the environment. Traditionally, safe levels of a chemical have been derived from the non-observable effect level (NOEL) estimated in laboratory toxicity bioassays with organisms which are representative of certain taxa. There are fundamental problems with the validity of this approach, both conceptual and statistical in nature. Firstly, the outdated NOEL concept is being replaced by the no-effect concentration (NEC) level, which assumes that toxic chemicals do not have any effect on a population of organisms at very low concentrations. Recent developments in ecotoxicology, however, suggest that some toxicants can produce effects at any concentration level provided their exposure time is sufficiently long. Consequently, risk assessment of these chemicals, which includes neonicotinoid insecticides, some carcinogenic substances and certain metallic compounds, may require entirely new approaches. Secondly, the traditional approach to toxicity testing is to consider dose or concentration-effect relationships at arbitrarily fixed exposure durations which are supposed to reflect âacuteâ or âchronicâ time scales. This approach measures the proportion of all exposed individuals responding by the end of those fixed exposure times. However, the endpoint values obtained this way cannot be linked to make predictions for the wide range of exposures encountered by humans or in the environment, thus leading to serious underestimates of actual risk. In order to overcome this handicap, an increasing number of researchers are using a variant of the traditional toxicity testing protocol which includes time to event (TTE) methods. This TTE approach measures the times to respond for all individuals, and provides information on the acquired doses as well as the exposure times needed for a toxic compound to produce any level of effect on the organisms tested. Consequently, extrapolations and predictions of toxic effects for any combination of concentration and time are now made possible. Examples are shown to demonstrate that this approach is superior to current toxicological testing procedures, and has important implications for risk assessment of chemicals, particularly when the chemical has delayed toxic effects in a time-dependent manner.
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