In the Spotlight
The Year in Review: AltTox Editorial Board members reflect on significant technology and policy developments in 2015
For the final “In the Spotlight” article of 2015, we asked AltTox Editorial Board members to identify what they saw as the most significant development for non-animal chemical safety testing, in the realms of technology or policy. Here is what some of them had to say.
Bas Blaauboer: “An important step forward is the acceptance by the OECD of alternatives for the Draize Eye test with rabbits (such as TG 491). After more than three decades many people have been working on getting rid of this very unreliable in vivo testing of chemicals on rabbit eyes, and finally it is now accepted that it can be done better. An important consequence of this is that the animal test is no longer a ‘gold standard’… perhaps more a ‘rusty standard’? We need to go for the platinum standard and that is human relevance.”
Emanuela Corsini: “In the field of skin sensitization, a great deal of success has been achieved in the in vitro assessment of skin sensitization potential of low molecular weight chemicals, with four methods successfully validated (i.e., the direct peptide reactivity assay (DRPA); the KeratinoSens; the human cell line activation assay (h-CLAT) and the IL-8 Luc assay) and OECD guidelines available or soon to be available. In February 2015, the OECD published Test No. 442D, In Vitro Skin Sensitisation ARE-Nrf2 Luciferase Test Method. Furthermore, several integrated testing strategies have been proposed which allow identification, classification, and labelling of potential skin sensitizers. The acceptance of these strategies by regulatory agencies will contribute to significantly reduce the use of animals, limiting in vivo testing to those chemicals for which estimation of induction sensitization level is necessary for effective risk assessment.
To achieve a complete replacement of animals in skin sensitization assessment, dose-response information and evaluation of relative skin sensitizing potency to support effective risk assessment are necessary. This will require a better understanding of the mechanisms underlying potency, pathway analysis, the selection of an appropriate immune-mediated response and marker(s) to serve as the basis, together with quantitative and qualitative relation between marker signatures and potency of a chemical in relation to the activation of specific immune response. Several groups worldwide are actively involved in this field.”
John R. (Jack) Fowle, III: “In my mind the most significant policy and technical developments in 2015 were EPA’s June 19, 2015 announcement of its plans to use high throughput assays and computational tools to screen chemicals for their ability to interact with the endocrine system rather than the largely animal-based approach used previously. This is one of the first uses of Tox21 alternative methods for regulatory use, and in combination with the EDSP21 Dashboard will accelerate the pace of screening, decrease costs, and reduce animal testing while providing better information to inform decisions about endocrine disruption.”
Albert Li: “International regulatory agencies and the pharmaceutical industry have continued to accept in vitro human hepatic systems for the assessment of human in vivo metabolic fate, pharmacokinetic, and drug-drug interaction properties, with cryopreserved human hepatocytes considered the gold standard. The application has now been extended to the evaluation of drug toxicity. Key to success: in vitro human-based system can provide human-specific information which, due to species difference, cannot be obtained with nonhuman animals. In vitro human-based experimental systems which retain human- and organ-specific properties are superior to in vivo experimental system with nonhuman animals.”
William Mundy: “Three-dimensional (3-D) cultures that mimic central nervous system structure promise to improve the study of neurological disorders, drug efficacy, and neurotoxicity. In vitro organogenesis of the central nervous system using human stem cells is now becoming a reality. Recent work by Schwartz et al. (2015) showed that human embryonic stem cell-derived neural, endothelial, mesenchymal, and microglia/macrophage precursors could self-assemble into 3-D neural constructs and accurately predict the neurotoxicity potential of a 60 chemical training set. These approaches move us closer to a human model system that will reduce the use of animals for neurotoxicity testing and provide data relevant to humans.”
Catherine Willett: “A particularly encouraging trend in 2015 was dramatic expansion of interest in Adverse Outcome Pathways. The concept of pathway-based approaches to integrated testing as a strategy for improving confidence in chemical management decisions was widely discussed at a number of international meetings and is gaining in attention and acceptance. In addition, guidance for developing and using AOPs continues to evolve, and thought-provoking manuscripts describing case studies and theory of use are published nearly every month. The AOP work plan at the Organization of Economic Cooperation and Development (OECD) continues to bloom, with more than 60 pathway projects in development. Strong participation in the AOP wiki and associated databases from a broad range of scientists is essential for building the infrastructure necessary to make this approach work. I’m looking forward to increased international participation in 2016.”
We would like to hear from AltTox readers, as well. Leave a comment below to tell us what you think were 2015’s most significant technology or policy developments for non-animal chemical safety testing.