Dose-dependent responses of metabolism and tissue injuries in clam Ruditapes philippinarum after subchronic exposure to cadmium

Energy balance is a fundamental requirement of stress adaptation and tolerance. We explore the links between metabolism, energy balance and stress tolerance using aquatic invertebrates as an example and demonstrate that using key parameters of energy balance (aerobic scope for growth, reproduction and activity; tissue energy status; metabolic rate depression; and compensatory onset of anaerobiosis) can assist in integrating the effects of multiple stressors and their interactions and in predicting the whole-organism and population-level consequences of environmental stress. We argue that limitations of both the amount of available energy and the rates of its acquisition and metabolic conversions result in trade-offs between basal maintenance of a stressed organism and energy costs of fitness-related functions such as reproduction, development and growth and can set limit to the tolerance of a broad range of environmental stressors. The degree of stress-induced disturbance of energy balance delineates transition from moderate stress compatible with population persistence (pejus range) to extreme stress where only time-limited existence is possible (pessimum range). It also determines the predominant adaptive strategy of metabolic responses (energy compensation vs. conservation) that allows an organism to survive the disturbance. We propose that energy-related biomarkers can be used to determine the conditions when these metabolic transitions occur and thus predict ecological consequences of stress exposures. Bioenergetic considerations can also provide common denominator for integrating stress responses and predicting tolerance limits under the environmentally realistic scenarios when multiple and often variable stressors act simultaneously on an organism. Determination of bioenergetic sustainability at the organism's level (or lack thereof) has practical implications. It can help identify the habitats and/or conditions where a population can survive (even if at the cost of reduced reproduction and growth) and those that are incapable of supporting viable populations. Such an approach will assist in explaining and predicting the species' distribution limits in the face of the environmental change and informing the conservation efforts and resource management practices. Copyright © 2012 Elsevier Ltd. All rights reserved. Show more

Abstract The Scientific Committee (SC) reconfirms that the benchmark dose (BMD) approach is a scientifically more advanced method compared to the NOAEL approach for deriving a Reference Point (RP). Most of the modifications made to the SC guidance of 2009 concern the section providing guidance on how to apply the BMD approach. Model averaging is recommended as the preferred method for calculating the BMD confidence interval, while acknowledging that the respective tools are still under development and may not be easily accessible to all. Therefore, selecting or rejecting models is still considered as a suboptimal alternative. The set of default models to be used for BMD analysis has been reviewed, and the Akaike information criterion (AIC) has been introduced instead of the log‐likelihood to characterise the goodness of fit of different mathematical models to a dose–response data set. A flowchart has also been inserted in this update to guide the reader step‐by‐step when performing a BMD analysis, as well as a chapter on the distributional part of dose–response models and a template for reporting a BMD analysis in a complete and transparent manner. Finally, it is recommended to always report the BMD confidence interval rather than the value of the BMD. The lower bound (BMDL) is needed as a potential RP, and the upper bound (BMDU) is needed for establishing the BMDU/BMDL per ratio reflecting the uncertainty in the BMD estimate. This updated guidance does not call for a general re‐evaluation of previous assessments where the NOAEL approach or the BMD approach as described in the 2009 SC guidance was used, in particular when the exposure is clearly smaller (e.g. more than one order of magnitude) than the health‐based guidance value. Finally, the SC firmly reiterates to reconsider test guidelines given the expected wide application of the BMD approach. Show more