The Three Rs (, , ) concept put forward by Russell and Burch now appears to be widely accepted. However, their warnings concerning reliance on animals as models for humans, the insurmountable problem of species differenc...The Three Rs (, , ) concept put forward by Russell and Burch now appears to be widely accepted. However, their warnings concerning reliance on animals as models for humans, the insurmountable problem of species differences and the impact of human variation, have been downplayed or even ignored. Schemes for harm-benefit analysis have been introduced, but the focus has largely been on harm to the animals, rather than on the direct and indirect benefit to humans, which is much more difficult to evaluate. Greater recognition should be given to the direct or indirect harm to humans resulting from the current over-reliance of biomedical research and testing on data obtained from animal experiments. That will be hard to achieve in the current climate, given the vigorous defence of animal experimentation by those with vested interests, confusion over responsibilities for regulating animal experimentation, hierarchies of regulatory authorities which require or limit experiments on animals, and exaggerated claims about the current availability of new approach methodologies (NAMs) and relevant and reliable strategies for their use. Those who defend animal experimentation at almost any cost must bear part of the responsibility for the human harms which result. Meanwhile, much greater effort should be put into the development, validation and application of new approaches not involving animals.
Thompson CV, Firman JW, Goldsmith MR
… +7 more, Grulke CM, Tan YM, Paini A, Penson PE, Sayre RR, Webb S, Madden JC
Altern Lab Anim
· 2021 Sep · PMID 34836462
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Across multiple sectors, including food, cosmetics and pharmaceutical industries, there is a need to predict the potential effects of xenobiotics. These effects are determined by the intrinsic ability of the substance, o...Across multiple sectors, including food, cosmetics and pharmaceutical industries, there is a need to predict the potential effects of xenobiotics. These effects are determined by the intrinsic ability of the substance, or its derivatives, to interact with the biological system, and its concentration-time profile at the target site. Physiologically-based kinetic (PBK) models can predict organ-level concentration-time profiles, however, the models are time and resource intensive to generate . Read-across is an approach used to reduce or replace animal testing, wherein information from a data-rich chemical is used to make predictions for a data-poor chemical. The recent increase in published PBK models presents the opportunity to use a read-across approach for PBK modelling, that is, to use PBK model information from one chemical to inform the development or evaluation of a PBK model for a similar chemical. Essential to this process, is identifying the chemicals for which a PBK model already exists. Herein, the results of a systematic review of existing PBK models, compliant with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) format, are presented. Model information, including species, sex, life-stage, route of administration, software platform used and the availability of model equations, was captured for 7541 PBK models. Chemical information (identifiers and physico-chemical properties) has also been recorded for 1150 unique chemicals associated with these models. This PBK model data set has been made readily accessible, as a Microsoft Excel spreadsheet, providing a valuable resource for those developing, using or evaluating PBK models in industry, academia and the regulatory sectors.
As non-animal alternatives gain acceptance, a need for harmonised testing strategies has emerged. Arguably the most physiologically-relevant model for assessing potential respiratory toxicants, that based on human precis...As non-animal alternatives gain acceptance, a need for harmonised testing strategies has emerged. Arguably the most physiologically-relevant model for assessing potential respiratory toxicants, that based on human precision-cut lung slices (hPCLS) has been utilised in many laboratories, but a variety of culture methodologies are employed. In this pilot study, combinations of three different hPCLS culture methods (dynamic organ roller culture (DOC), air-liquid interface (ALI) and submersion) and various media (based on E-199, DMEM/F12 and RPMI-1640) were compared. The hPCLS were assessed in terms of their viability and responsiveness to challenge. The endpoints selected to compare the medium-method (M-M) combinations, which included histological features and viability, were evaluated at day 14 (D14) and day 28 (D28); protein and adenylate kinase (AK) content, and cytokine response to immunostimulants (lipopolysaccharide (LPS) at 5 μg/ml; polyinosinic:polycytidylic acid (Poly I:C) at 15 μg/ml) were evaluated at D28 only. Based on the set of endpoints assessed at D28, it was clear that certain culture conditions significantly affected the hPCLS, with the tissue retaining more of its native features and functionality (in terms of cytokine response) in some of the M-M combinations tested more than others. This pilot study indicates that the use of appropriate M-M combinations can help maintain the health and functional responses of hPCLS, and highlights the need for the standardisation of culture conditions in order to facilitate effective inter-laboratory comparisons and encourage greater acceptance by the regulatory community.
The Butantan Institute is a pioneering Brazilian health sciences institution, which also houses a large science park with museums that contribute to ongoing science education for schools and the wider community. In recen...The Butantan Institute is a pioneering Brazilian health sciences institution, which also houses a large science park with museums that contribute to ongoing science education for schools and the wider community. In recent years, as part of Butantan Institute's ™, zebrafish embryos have been used for the dissemination of scientific knowledge during on-site events and as part of outreach campaigns to non-scientific audiences, mostly children. The aim of this work is mainly to demystify the activities of the scientific researcher, highlight the role of science in the furthering of knowledge, and increase public interest and confidence in science. In this article, the Institute's 'Plataforma Zebrafish Open Doors' programme is described, which offered guided tours of the laboratory facilities. The tours gave visitors the opportunity to observe zebrafish research and embryo development, and to use the knowledge gained from this experience as a framework for understanding fundamental ethical issues. During the 2-day event, around 800 visitors (most of them school-age children) attended. Together with the guided tours, our experience of outreach offered meaningful opportunities to bring children and members of the public closer to science and 'real-life' scientists, hopefully inspiring and encouraging the next generation of scientists. It also gave the scientists an opportunity to engage more closely with wider society. We believe that these activities also substantially contribute to the wider dissemination of relevant experimental results that have been obtained with public funding and that impact society in general.
Two cell lines derived from the brain and heart of a Pacific white snook specimen () were developed and evaluated in terms of their responsiveness to glyphosate-induced cytotoxicity. The cells were grown in Leibovitz-15...Two cell lines derived from the brain and heart of a Pacific white snook specimen () were developed and evaluated in terms of their responsiveness to glyphosate-induced cytotoxicity. The cells were grown in Leibovitz-15 (L-15) medium supplemented with 10% fetal bovine serum (FBS) and were passaged 36 times. Growth was tested at different concentrations of FBS (5, 10 and 20%) at 27°C. The cell lines were cryopreserved at different passages and were successfully thawed, with a survival rate greater than 80% without detectable contamination. At passage 36, the cells were used to assess the deleterious effects of glyphosate, and cell proliferation was measured by direct counting and with the MTT assay. Similar LC values were obtained with both methods. Although the principles behind these two assessment methods differ, our results show that both are suitable for evaluating glyphosate toxicity. In addition, heart- and brain-derived cells showed similar sensitivity, suggesting that the same mode of action might be responsible for the toxicity of glyphosate at the cellular level. The newly developed Pacific white snook brain and heart cell lines could be useful to investigate cellular and molecular mechanisms of toxicity, satisfying the need to reduce the use of animals in experiments. Glyphosate-related toxicological data obtained in the present study will allow us to continue investigating the effects of this herbicide directly on brain and heart fish cells since similar studies have only been carried out on either live organisms or on human cell lines such as neuroblastoma, which are immortalised by oncogenes or similar.
Animal use for testing chemicals under REACH continues to increase, despite advances in non-animal safety science during the past 15 years. The application of modern science and technology, and the use of 'next generatio...Animal use for testing chemicals under REACH continues to increase, despite advances in non-animal safety science during the past 15 years. The application of modern science and technology, and the use of 'next generation' weight-of-evidence assessment approaches, are embedded in EU guidance for establishing the safety of cosmetics and foods - and of the ingredients used in these products. However, this is still not the case for the regulation of chemicals. Under the new Chemicals Strategy for Sustainability, thought leaders in human health and environmental protection are calling on the European Commission to quickly embrace the benefits of modern and innovative non-animal safety science, in place of outdated animal testing, if the EU is to be a leader in safe and sustainable innovation under the European Green Deal transformational change ambitions. The European Commission also needs to enable companies to meet their legal obligation to only conduct animal testing as a last resort, by providing a more flexible, science-based and consistent regulatory framework for assuring chemical safety, which supports the integration of data from different sources. We are at a tipping point for closing the gap between regulatory chemicals testing and modern safety science. It is time to join forces, across policy makers, scientists, regulators and lawyers, to lead the paradigm shift needed to deliver what EU citizens want - namely, chemicals and products that are safe and sustainable, without resorting to animal testing.
Native human skin has been reported in the literature as being an important experimental model for studying skin biology. Studies performed by our group have shown that skin, from elective plastic surgery, maintains the...Native human skin has been reported in the literature as being an important experimental model for studying skin biology. Studies performed by our group have shown that skin, from elective plastic surgery, maintains the biological characteristics of native skin under specific culture conditions. As such, it might be a feasible model for the safety and efficacy testing of topical substances. While Brazil is at the forefront of global regulation implementation, Brazilian researchers are not always able to transfer certain widely used protocols to their laboratories, particularly protocols that involve the use of reconstructed tissues with limited viability, such as those for skin corrosion (OECD TG 431) and irritation testing (OECD TG 439). In this study, we investigated the applicability of the skin model to the evaluation of irritation and corrosion potential of a number of proficiency substances described in TG 431 and TG 439. The skin fragments were standardised in size and diameter, and placed into cell culture inserts. The experimental protocol was conducted according to TG 431 and TG 439. The results obtained show that skin could represent a promising tool for the evaluation of irritation and corrosion potential of substances (subject to inclusion and exclusion criteria), as recommended by OECD guidelines. While this is a proof-of-concept study, the use of skin should be considered for such testing.