Abstract

We present a model to identify the effects of low toxicant concentrations. Due to inadequate models, such effects have so far often been misinterpreted as random variability. Instead, a tri-phasic relationship describes the effects of a toxicant when a broad range of concentrations is assessed: i) at high concentrations where substantial mortality occurs (LC50), we confirmed the traditional sigmoidal response curve (ii) at low concentrations about 10 times below the LC50, we identified higher survival than previously modelled, and (iii) at ultra-low concentrations starting at around 100 times below the LC50, higher mortality than previously modelled. This suggests that individuals benefit from low toxicant stress. Accordingly, we postulate that in the absence of external toxicant stress individuals are affected by an internal “System Stress” (SyS) and that SyS is reduced with increasing strength of toxicant stress. We show that the observed tri-phasic concentration-effect relationship can be modelled on the basis of this approach. Here we revealed that toxicant-related effects (LC5) occurred at remarkably low concentrations, 3 to 4 orders of magnitude below those concentrations inducing strong effects (LC50). Thus, the ECx-SyS model presented allows us to attribute ultra-low toxicant concentrations to their effects on individuals. This information will contribute to performing a more realistic environmental and human risk assessment.

Highlights

  • We present a model to identify the effects of low toxicant concentrations

  • All 6 experiments revealed a tri-phasic concentration-response relationship: at low toxicant concentrations (0.03 μg/L) slight mortality compared to the control (1st phase), at medium concentrations (0.3 μg/L) lower effects compared to the control (2nd phase), and at high concentrations (>1 μg/L) the traditional sigmoidal response curve (3rd phase)

  • We show that the traditional fitting of concentration-response only identifies a reduction in the LC5 compared to the LC50 by a factor of 7 (Fig. 4)

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Summary

Introduction

We present a model to identify the effects of low toxicant concentrations. Due to inadequate models, such effects have so far often been misinterpreted as random variability. A tri-phasic relationship describes the effects of a toxicant when a broad range of concentrations is assessed: i) at high concentrations where substantial mortality occurs (LC50), we confirmed the traditional sigmoidal response curve (ii) at low concentrations about 10 times below the LC50, we identified higher survival than previously modelled, and (iii) at ultra-low concentrations starting at around 100 times below the LC50, higher mortality than previously modelled This suggests that individuals benefit from low toxicant stress. A meta-study investigating the concentration-effect relationship of various toxicants with a concentration range of about 2 orders of magnitude found that out of 26 studies more than two thirds of studies (18) showed a sub-hormetic reduction in survival[1] When such low concentrations of toxicants are tested, a tri-phasic concentration-response relationship becomes apparent with increasing toxicant concentrations: strong mortality at high concentrations, increasing survival at low, hormetic concentrations and small adverse effects at ultra-low subhormetic concentrations. We expect that such an approach is the key to identify and predict biological responses in the range of low and ultra-low concentrations

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