ATLA 41.6, December 2013

//ATLA 41.6, December 2013

Editorial: The 2012 Lush Prize Awards

Kelly A. BéruBé and Katy Brown

The Lush Prize awards represent a collaboration between Lush Cosmetics and Ethical Consumer Research Association (Ethical Consumer). Lush is a campaigning manufacturer and retailer of fresh handmade cosmetics, with shops in 49 countries.

The Ethical Consumer is a UK-based research and consultancy co-operative, focused on working with companies and consumers around effective ethical choices.

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2017-01-09T06:38:56+00:00 Tags: |

Medical Waste Tissues — Breathing Life back into Respiratory Research

Kelly A. BéruBé

With the advent of biobanks to store human lung cells and tissues from patient donations and from the procurement of medical waste tissues, it is now possible to integrate (both spatially and temporally) cells into anatomically-correct and physiologically-functional tissues. Modern inhalation toxicology relies on human data on exposure and adverse effects, to determine the most appropriate risk assessments and mitigations for beneficial respiratory health. A point in case is the recapitulation of airway tissue, such as the bronchial epithelium, to investigate the impact of air pollution on human respiratory health. The bronchi are the first point of contact for inhaled substances that bypass defences in the upper respiratory tract. Animal models have been used to resolve such inhalation toxicology hazards. However, the access to medical waste tissues has enabled the Lung Particle Research Group to tissue-engineer the Micro-Lung™ and Metabo-Lung™ cell culture models, as alternatives to animals in basic research and in the safety testing of aerosolised consumer goods. The former model favours investigations focused on lung injury and repair mechanisms, and the latter model provides the element of metabolism, through the co-culturing of lung and liver (hepatocyte) cells. These innovations represent examples of the animal-free alternatives advocated by the 21st century toxicology paradigm, whereby human-derived cell/tissue data will lead to more accurate and more-reliable public health risk assessments and therapeutic mitigations (e.g. exposure to ambient air pollutants and adverse drug reactions) for lung disease.
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Update from the Japanese Center for the Validation of Alternative Methods (JaCVAM)

Hajime Kojima

The Japanese Center for the Validation of Alternative Methods (JaCVAM) was established in 2005 to promote the use of alternatives to animal testing in regulatory studies, thereby replacing, reducing, or refining the use of animals, according to the Three Rs principles. JaCVAM assesses the utility, limitations and suitability for use in regulatory studies, of test methods needed to determine the safety of chemicals and other materials. JaCVAM also organises and performs validation studies of new test methods, when necessary. In addition, JaCVAM co-operates and collaborates with similar organisations in related fields, both in Japan and internationally, which also enables JaCVAM to provide input during the establishment of guidelines for new alternative experimental methods. These activities help facilitate application and approval processes for the manufacture and sale of pharmaceuticals, chemicals, pesticides, and other products, as well as for revisions to standards for cosmetic products. In this manner, JaCVAM plays a leadership role in the introduction of new alternative experimental methods for regulatory acceptance in Japan.
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Animal-free Toxicology: The Use of Human Tissue to Replace the Use of Animals — Examples from Human Biomonitoring and Human Placental Transport Studies

Lisbeth E. Knudsen

Human data on exposure and adverse effects are the most appropriate for human risk assessment, and modern toxicology focuses on human pathway analysis and the development of human biomarkers. Human biomonitoring and human placental transport studies provide necessary information for human risk assessment, in accordance with the legislation on chemical, medicine and food safety. Toxicology studies based on human mechanistic and exposure information can replace animal studies. These animal-free approaches can be further supplemented by new in silico methods and chemical structure–activity relationships. The inclusion of replacement expertise in the international Three Rs centres, the ongoing exploration of alternatives to animal research, and the improvement of conditions for research animals, all imply the beginning of a paradigm shift in toxicology research toward the use of human data.
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A Vision Becoming Reality

Gill Langley

Non-animal science in toxicology and health research has been progressing for decades, but
only now is it being seen widely as advanced science. The emergence of novel human biology-based tools and models, combined with legislative and regulatory change, a 21st century concept for toxicology, continuing failures in the drug pipeline, and systematic critiques of animal models, have created a pivotal moment of change. The leading edge is starting to become the norm. Humans and other animals are likely to benefit as a result.
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Humane Society International’s Global Campaign to End Animal Testing

Troy Seidle

The Research & Toxicology Department of Humane Society International (HSI) operates a multifaceted and science-driven global programme aimed at ending the use of animals in toxicity testing and research. The key strategic objectives include: a) ending cosmetics animal testing worldwide, via the multinational Be Cruelty-Free campaign; b) achieving near-term reductions in animal testing requirements through revision of product sector regulations; and c) advancing humane science by exposing failing animal models of human disease and shifting science funding toward human biology-based research and testing tools fit for the 21st century. HSI was instrumental in ensuring the implementation of the March 2013 European sales ban for newly animal-tested cosmetics, in achieving the June 2013 cosmetics animal testing ban in India as well as major cosmetics regulatory policy shifts in China and South Korea, and in securing precedent-setting reductions in in vivo data requirements for pesticides in the EU through the revision of biocides and plant protection product regulations, among others. HSI is currently working to export
these life-saving measures to more than a dozen industrial and emerging economies.
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Adverse Outcome Pathway-based Screening Strategies for an Animal-free Safety Assessment of Chemicals

Brigitte Landesmann, Milena Mennecozzi, Elisabet Berggren and Maurice Whelan

Currently, the assessment of risk to human health from exposure to manufactured chemicals is mainly based on experiments performed on living animals (in vivo). Substantial efforts are being undertaken to develop alternative solutions to in vivo toxicity testing. This new paradigm, based on the Mode-of-Action (MoA) framework, postulates that any adverse human health effect caused by exposure to an exogenous substance can be described by a series of causally-linked biochemical or biological key events with measurable parameters. The elaboration of mechanistic knowledge through literature research is necessary for a MoA-driven design of integrated testing strategies using in vitro methods for in vivo predictions. The objective of our ongoing research is to demonstrate the feasibility of an integrated approach to predict human toxicity following the Adverse Outcome Pathway (AOP) framework. In our previous work on MoA with the HepaRG cell model, we developed a strategy to identify chemicals that were hepatotoxic. This pioneered an innovative way of using data from in vitro experiments to group chemicals based on their MoA, which is likely to be an important step in a toxicity testing strategy.
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A Proposed Study on the Transplacental Transport of Parabens in the Human Placental Perfusion Model

Line Mathiesen, Giuseppina Zuri, Maria H. Andersen and Lisbeth E. Knudsen

Human exposure to parabens as a preservative used in personal care products is of increasing concern, as there is evidence from in vivo and in vitro studies of hormone disruption in association with exposure to parabens. Transport across the placenta could be critical for risk assessment, but the available data are sparse. The aim is to develop a method for estimating fetal exposure, via the placenta, to the most  commonly-used parabens, by using a human placental perfusion model. The use of human tissue is vital for determining human fetal exposure, because animal studies are of little relevance, since the placenta exhibits significant interspecies variation. An HPLC model is currently being established to simultaneously quantify four different parabens, namely, methylparaben, ethylparaben, propylparaben and butylparaben, and their main metabolite, p-hydroxybenzoic acid. With this model, we aim to determine the transport kinetics of these parabens across the human placenta, and to investigate placental metabolism, including differences in transport due to molecular characteristics. This will facilitate assessment of the risks associated with the use of paraben-containing products during pregnancy.
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Cryopreserved Human Whole Blood: A Human-based In Vitro Immunotoxicological System

Félix E. Rivera-Mariani

The airborne environment poses numerous human health risks, including potential exposure to particulate matter and to fungal bioaerosols with pro-inflammatory capabilities. The utility of animal models in the study of the human health effects of these exposures is often limited. This is due to the necessity for a high-throughput of samples and the high financial costs involved, as well as various associated animal welfare issues. In addition, animal models might not appropriately predict the responses of humans to pro-inflammatory stimuli. Here are discussed the recent applications of a human-based assay, the cryopreserved human whole blood system, to study the human health effects of exposures to particulate matter and to the less-studied fungal spores of higher fungi (phylum Basidiomycota or ‘true mushrooms’).
Evidence is provided to support the utility of the human-based assay in the fields of environmental health and medical mycology, for the evaluation of common paradigms in environmental health studies, and to highlight the potential human health effects of spores of basidiomycete fungi.
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