The vision of toxicity testing in the 21st century: moving from discussion to action.
ABSTRACT Over the past year, a series on commentaries have appeared in the Toxicological Sciences Forum Series related to the 2007 National Research Council (NRC) publication, Toxicity Testing in the 21st Century: A Vision and A Strategy. The first article in the series provided an overview of the vision and was accompanied by an editorial by the three editors of Toxicological Sciences. During the past year, eight invited commentaries from the academic, industrial, and regulatory sectors have provided diverse perspectives on the vision, noted challenges to its implementation, and highlighted aspects of toxicity testing that were not addressed in the original NRC report. Here, we offer a summary of the main points raised by the commentators in tabular form, identify a number of common themes, and finish the series by providing our perspective on several key issues in charting the path forward to move from discussion to action.
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ABSTRACT: Understanding the toxic mechanisms by which organisms cope to environmental stressful conditions is a fundamental question for ecotoxicology. In this study, we evaluated biochemical responses and hydrocarbons bioaccumulation of the mangrove oyster Crassostrea brasiliana exposed for 96 h to four sublethal concentrations of diesel fuel water-accommodated fraction (WAF). For that purpose, enzymatic activities (SOD, CAT, GPx, GR, G6PDH, GST and GGT), HSP60 and HSP90 immunocontent and lipid peroxidation (LPO) levels were determined in the gill and digestive gland of oysters and related to the hydrocarbons accumulated in the whole soft tissues. The results of this study revealed clear biochemical responses to diesel fuel WAF exposure in both tissues of the oyster. The capacity of C. brasiliana to bioaccumulate aliphatic and aromatic hydrocarbons in a dose-dependent manner is a strong indication of its suitability as a model in biomonitoring programs along the Brazilian coast, which was also validated by the response of the antioxidant defenses, phase II biotransformation and chaperones. HSP60 levels and GGT activity were the most promising biomarkers in the gill, while GST and GR activities stood out as suitable biomarkers for the detection of diesel toxicity in the digestive gland. The decrease of SOD activity and HSP90 levels may also reflect a negative effect of diesel exposure regardless the tissue. The present results provide a sound preliminary report on the biochemical responses of C. brasiliana challenged with a petroleum by-product and should be carefully considered for use in the monitoring of oil and gas activities in Brazil.Aquatic toxicology (Amsterdam, Netherlands) 09/2011; 105(3-4):652-60. · 3.12 Impact Factor
- Chemico-biological interactions 01/2014; 209:14-24. · 2.46 Impact Factor
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ABSTRACT: Despite wide-spread consensus on the need to transform toxicology and risk assessment in order to keep pace with technological and computational changes that have revolutionized the life sciences, there remains much work to be done to achieve the vision of toxicology based on a mechanistic foundation. To this end, a workshop was organized to explore one key aspect of this transformation - the development of Pathways of Toxicity as a key tool for hazard identification based on systems biology. Several issues were discussed in depth in the workshop: The first was the challenge of formally defining the concept of a Pathway of Toxicity (PoT), as distinct from, but complementary to, other toxicological pathway concepts such as mode of action (MoA). The workshop came up with a preliminary definition of PoT as "A molecular definition of cellular processes shown to mediate adverse outcomes of toxicants". It is further recognized that normal physiological pathways exist that maintain homeostasis and these, sufficiently perturbed, can become PoT. Second, the workshop sought to define the adequate public and commercial resources for PoT information, including data, visualization, analyses, tools, and use-cases, as well as the kinds of efforts that will be necessary to enable the creation of such a resource. Third, the workshop explored ways in which systems biology approaches could inform pathway annotation, and which resources are needed and available that can provide relevant PoT information to the diverse user communities.ALTEX. 10/2013;