Toxicology for the Twenty-First Century

Department of Environmental Health Sciences at the Johns Hopkins University Bloomberg School of Public Health, USA.
Nature (Impact Factor: 42.35). 08/2009; 460(7252):208-12. DOI: 10.1038/460208a
Source: PubMed

ABSTRACT The testing of substances for adverse effects on humans and the
environment needs a radical overhaul if we are to meet the challenges of
ensuring health and safety.

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Available from: Thomas Hartung, Aug 27, 2015
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    • "In this way, REACH is expected to play a major role in driving the scientific validation and regulatory acceptance of alternative testing methods (Hartung, 2009, 2010). Many components of the WHO/IPCS IRA Framework (2001) can already be found in the REACH RA approach (Vermeire, 2009). "
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    ABSTRACT: The vision of a sustainable and safe use of chemicals to protect human health, preserve the environment and main- tain the ecosystem requires innovative and more holistic approaches to risk assessment (RA) in order to better in- form decision making. Integrated risk assessment (IRA) has been proposed as a solution to current scientific, societal and policy needs. It is defined as the mutual exploitation of environmental risk assessment (ERA) for human health risk assessment (HHRA) and vice versa in order to coherently and more efficiently characterize an overall risk to humans and the environment for better informing the risk analysis process. Extrapolating between species which are relevant for HHRA and ERA requires a detailed understanding of pathways of toxicity/modes of action (MoA) for the various toxicological endpoints. Significant scientific advances, changes in chemical legislation, and increas- ing environmental consciousness have created a favourable scientific and regulatory environment to develop and promote the concept and vision of IRA. An initial proof of concept is needed to foster the incorporation of IRA approaches into different chemical sectorial regulations and demonstrate their reliability for regulatory purposes. More familiarity and confidence with IRA will ultimately contribute to an overall reduction in in vivo toxicity testing requirements. However, significant progress will only be made if long-term support for MoA-related research is secured. In the short term, further exchange and harmonization of RA terminology, models and methodologies across chemical categories and regulatory agencies will support these efforts. Since societal values, public perceptions and cultural factors are of increasing importance for the acceptance of risk analysis and successful implementation of risk mitigation measures, the integration of socio-economic analysis and socio-behavioural considerations into the risk analysis process may help to produce a more effective risk evaluation and consideration of the risks and benefits associated with the use of chemicals.
    Science of The Total Environment 04/2015; · 4.10 Impact Factor
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    • "sub-chronic, reproductive toxicity). However, as previously mentioned, these guidelines are very resource intensive in terms of animals, time and overall cost (Rovida and Hartung 2009; Tsuji and Crofton 2012) and have been used only for a very limited number of pesticides and industrial chemicals. This highlights the pressing need for alternative methodologies that can more rapidly and cost-effectively screen large numbers of chemicals for their potential to cause DNT or investigate mechanisms to provide information on human relevance (Crofton et al. 2012). "
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    ABSTRACT: A major problem in developmental neurotoxicity (DNT) risk assessment is the lack of toxicological hazard information for most compounds. Therefore, new approaches are being considered to provide adequate experimental data that allow regulatory decisions. This process requires a matching of regulatory needs on the one hand and the opportunities provided by new test systems and methods on the other hand. Alignment of academically and industrially driven assay development with regulatory needs in the field of DNT is a core mission of the International STakeholder NETwork (ISTNET) in DNT testing. The first meeting of ISTNET was held in Zurich on 23-24 January 2014 in order to explore the concept of adverse outcome pathway (AOP) to practical DNT testing. AOPs were considered promising tools to promote test systems development according to regulatory needs. Moreover, the AOP concept was identified as an important guiding principle to assemble predictive integrated testing strategies (ITSs) for DNT. The recommendations on a road map towards AOP-based DNT testing is considered a stepwise approach, operating initially with incomplete AOPs for compound grouping, and focussing on key events of neurodevelopment. Next steps to be considered in follow-up activities are the use of case studies to further apply the AOP concept in regulatory DNT testing, making use of AOP intersections (common key events) for economic development of screening assays, and addressing the transition from qualitative descriptions to quantitative network modelling.
    Archive für Toxikologie 01/2015; 89(2). DOI:10.1007/s00204-015-1464-2 · 5.08 Impact Factor
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    • "It has been suggested that the " gold standard " for eye irritation should be the human response (Bagley et al., 2006) and that ideally, a testing strategy to determine if a substance is harmful to humans would utilize an extremely high number of human subjects in order to faithfully represent human diversity. They would have to be unknowingly exposed to a substance under realistic conditions and the effects assessed (Hartung, 2009). However, such experimentation is both unrealistic and unethical. "
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    ABSTRACT: Given the hazardous nature of many materials and substances, ocular toxicity testing is required to evaluate the dangers associated with these substances after their exposure to the eye. Historically, animal tests such as the Draize test were exclusively used to determine the level of ocular toxicity by applying a test substance to a live rabbit’s eye and evaluating the biological response. In recent years, legislation in many developed countries has been introduced to try to reduce animal testing and promote alternative techniques. These techniques include ex vivo tests on deceased animal tissue, computational models that use algorithms to apply existing data to new chemicals and in vitro assays based on two dimensional (2D) and three dimensional (3D) cell culture models. Here we provide a comprehensive overview of the latest advances in ocular toxicity testing techniques, and discuss the regulatory framework used to evaluate their suitability.
    Toxicology 11/2014; 327C:32-46. DOI:10.1016/j.tox.2014.11.003 · 3.75 Impact Factor
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