Toward an evidence-based toxicology

Abstract

<jats:p> The increasing demands on toxicology of large-scale risk assessment programmes for chemicals and emerging or expanding areas of chemical use suggest it is timely to review the toxicological toolbox. Like in clinical medicine, where an evidence-based medicine (EBM) is critically reviewing traditional approaches, toxicology has the opportunity to reshape and enlarge its methodology and approaches on the basis of compounded scientific knowledge. Such revision would have to be based on structured reviews of current practice, ie, assessment of test performance characteristics, mechanistic understanding, extended quality assurance, formal validation and the use of integrated testing strategies. This form of revision could optimize the balance between safety, costs and animal welfare, explicitly stating and, where possible, quantifying uncertainties. After a self-critical reassessment of current practices and evaluation of the thus generated information, such an evidence-based toxicology (EBT) promises to make better use of resources and to increase the quality of results, facilitating their interpretation. It shall open up hazard and also risk assessments to new technologies, flexibly accommodating current and future mechanistic understanding. An EBT will be better prepared to answer the continuously growing safety demands of modern societies. </jats:p>

Expert Review for GHS Classification of Chemicals on Health Effects

“…Without an explanation of how evidence is "weighed" or "weighted", the WOE approach may be to be a "black box" of scientific judgment 13) . To keep transparency of expert reviews, the review should be objective and taken into consideration of evidence based toxicology 16) .…”

An economic approach to non-animal toxicity testing for skin sensitisation

“…Uncertainties should be transparently addressed and documented. Furthermore, different cost components need to be acknowledged, in particular welfare losses from misclassifications (Hoffmann and Hartung, 2006), monetary costs of regulatory validation of testing strategies (Schaafsma et al, 2009), animal welfare loss (Hartung et al, 2013;Rovida et al, 2015) and direct testing costs Hartung et al, 2013;Rovida et al, 2015). Jaworska and Hoffmann (2010) indicated that the process of integrating information from toxicity testing should allow for evidence maximisation while considering factors such as costs, animal welfare and test complexity for an optimal selection of information sources (computational, in chemico and in vitro methods).…”

“…Lewis et al, 2007;Kinsner-Ovaskainen et al, 2009;Schaafsma et al, 2009;Krewski et al, 2010;De Wever et al, 2012 Protect animal welfare; reduce/minimise the number of animal used in testing or animal suffering when animal testing is considered unavoidable. Hoffmann and Hartung, 2006;Lewis et al, 2007;Hoffmann et al, 2008;Schaafsma et al, 2009;Krewski et al, 2010 Evaluation of cost-effectiveness or efficiency. Hoffmann and Hartung, 2006;Lewis et al, 2007;Hoffmann et al, 2008;Schaafsma et al, 2009;Krewski et al, 2010 Conceptual requirements for DA development Data integration and final conclusion based on a coherent methodology (e.g.…”

“…Hoffmann and Hartung, 2006;Lewis et al, 2007;Hoffmann et al, 2008;Schaafsma et al, 2009;Krewski et al, 2010 Evaluation of cost-effectiveness or efficiency. Hoffmann and Hartung, 2006;Lewis et al, 2007;Hoffmann et al, 2008;Schaafsma et al, 2009;Krewski et al, 2010 Conceptual requirements for DA development Data integration and final conclusion based on a coherent methodology (e.g. unambiguous algorithm).…”

“…Hoffmann et al, 2008;Dellarco et al, 2010;De Wever et al, 2012 Use of scientifically valid (accurate, reliable) and adequate information. Hoffmann and Hartung, 2006;Ahlers et al, 2008;Schaafsma et al, 2009;Krewski et al, 2010;Schoeters, 2010;De Wever et al, 2012 Evaluation of the performance (e.g. predictivity, goodness-of-fit, robustness) of individual testing methods and strategies.…”