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Recommendations to address uncertainties in environmental risk assessment using toxicokinetics-toxicodynamics modelsuse asterix (*) to get italics
Virgile Baudrot and Sandrine CharlesPlease use the format "First name initials family name" as in "Marie S. Curie, Niels H. D. Bohr, Albert Einstein, John R. R. Tolkien, Donna T. Strickland"
<p>Providing reliable environmental quality standards (EQS) is a challenging issue for environmental risk assessment (ERA). These EQS are derived from toxicity endpoints estimated from dose-response models to identify and characterize the environmental hazard of chemical compounds as those released by human activities. The classical toxicity endpoints are the x% effect/lethal concentrations at a specific time (i.e., EC/LC(x,t)), or the multiplication factors applied to environmental exposure profiles leading to x% of effect reduction at a specific time (i.e., MF(x,t)). However, classical dose-response models used to estimate the toxicity endpoints have some weaknesses such as their dependency on observation time-points which are likely to differ between species. Also, real exposure profiles are hardly ever constant over time, what makes impossible the use of classical dose-response models and compromises the derivation of MF(x,t), actually designed to tackle time-variable exposure profiles. When dealing with survival or immobility toxicity test data, these issues can be overcome with the use of the General Unified Threshold model of Survival (GUTS), a toxicokinetics-toxicodynamics (TKTD) model, providing an explicit framework to analyze both time and concentration-dependent data sets, as well as a mechanistic derivation of EC/LC(x,t) and MF(x,t) whatever x and at any time of interest. In addition, the assessment of a risk is inherently built upon probability distributions, so that the next critical step for ERA is to characterize uncertainties of toxicity endpoints, and sequentially of EQS. The innovative approach investigated in our paper is the use of the Bayesian framework to deal with uncertainties raising in the calibration process and propagated all along the successive prediction steps until the LC(x,t) and MF(x,t) derivations. We also explored the mathematical properties of LC(x,t) and MF(x,t) as well as the impact of different experimental designs in order to provide some recommendations for a robust derivation of toxicity endpoints leading to reliable EQS.</p> should fill this box only if you chose 'All or part of the results presented in this preprint are based on data'. URL must start with http:// or https://
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Survival models ; Dose-Response ; GUTS ; Lethal Concentration ; Multiplication Factor ; Margin of safety ; Environmental Risk Assessment
NonePlease indicate the methods that may require specialised expertise during the peer review process (use a comma to separate various required expertises).
Chemical ecology, Ecotoxicology, Experimental ecology, Statistical ecology
No need for them to be recommenders of PCIEcology. Please do not suggest reviewers for whom there might be a conflict of interest. Reviewers are not allowed to review preprints written by close colleagues (with whom they have published in the last four years, with whom they have received joint funding in the last four years, or with whom they are currently writing a manuscript, or submitting a grant proposal), or by family members, friends, or anyone for whom bias might affect the nature of the review - see the code of conduct
e.g. John Doe []
2018-06-27 21:33:30
Luis Schiesari