Alternative methods in toxicity testing: the current approach

Abstract

Alternative methods are being developed to reduce, refine, and replace (3Rs) animals used in experiments, aimed at protecting animal welfare. The present study reports alternative tests which are based on the principles of the 3Rs and the efforts made to validate these tests. In Europe, several methodologies have already been implemented, such as tests of irritability, cell viability, and phototoxicity as well as in vitro mathematical models together with the use of in silico tools. This is a complex process that spans from development to regulatory approval and subsequent adoption by various official entities. Within this regulatory framework is REACH, the European Community Regulation for chemicals and their safe use. In Brazil, the BraCVAM (Brazilian Center for the Validation of Alternative Methods) was recently established to validate alternative methods and stimulate incorporation of new methodologies. A new vision of toxicology is emerging for the 21st century (Tox-21), and the subsequent changes are shaping a new paradigm.Uniterms: Toxicology/alternative methods. Toxicological analysis/alternative methods. Toxicology/21st. century. Animals/use in experiments.Métodos alternativos estão sendo desenvolvidos para a redução, o refinamento e a substituição (3R) do número de animais utilizados em experimentos, visando ao seu bem-estar. Esses testes alternativos baseiam-se no princípio dos 3R e esforços têm sido empregados para que sejam validados. Na Europa, diversas metodologias já foram implantadas tais como: testes de irritabilidade, testes de viabilidade celular, testes de fototoxicidade e modelos matemáticos in vitro, além do uso de ferramentas in silico. Esse é um processo complexo, que abrange desde o seu desenvolvimento até a aceitação regulatória e posterior adoção por diversas organizações oficiais. No contexto regulatório está o REACH, o Regulamento da Comunidade Européia, para produtos químicos e sua utilização segura. No Brasil, o BraCVAM (Centro Brasileiro de Validação de Métodos Alternativos) foi recentemente estabelecido para validação de métodos alternativos e estímulo à incorporação de novas metodologias. Uma nova visão de toxicologia vem surgindo para o século XXI (Tox-21) e as mudanças ocasionadas promoverão um novo paradigma.Unitermos: Toxicologia/métodos alternativos. Análise toxicológica/métodos alternativos. Toxicologia/ século 21. Animais/uso em experimentos.

Current methodologies in assessing toxicity of natural products

“…This combination will be helpful to determine the likelihood of adverse effects from "low-dose" exposure, as well as to assess variation among individuals in specific susceptible groups. 8 TK data are an essential piece of information for inter species extrapolation, route-to-route extrapolation and for mechanistic consideration, visual examination of cell cultures after their exposure to different susbstances, including nanoparticles is very important for in vitro toxicity assessment. 9,10 The use of silico models to describe the cellular system increases our understanding of the (adverse) effects observed in in vitro systems, and should also improve the translation of in vitro data to the in vivo situation.…”

“…The Organization for Economic Cooperation and Development (OECD) recognizes the importance of in vitro methods to fully capture the complexity of the toxic response in an intact organism. 8 In vitro tests offer several advantages, including an apreciable amount of intrinsic toxicity information, controlled testing conditions; a high level of standardization; a reduction in variability between experiments; low cost testing; a small amount of material needed; a limited amount of toxic waste, cells, and human tissues used as well as transgenic cells carrying human genes; and reduced animal testing (reduction of the number of animals, and refinement of the techniques with less animal stress). 11 Remarkable amount of information can be gathered about intrinsic toxicity and molecular mechanisms in unique type of cells, at appropriate testing conditions.…”

Phytotoxicity of extracts of Myrciaria dubia (Kunth) McVaugh bioprocessed in vegetable crop sensitive to allelochemicals

“…Considering the current methods of toxicological evaluation, in vitro tests offer several advantages, low cost; a small amount of material required; a limited amount of toxic waste, cells and human tissues used; as well as transgenic cells carrying human genes and reduced animal testing (Araujo et al, 2014). According to Araujo and Monteiro (2005), seeds germination and plant growth bioassays are the most common techniques used to assess the phytotoxic compounds According to Trautmann and Krasny (1997), it enables the determination of whether there are, in the compound or in the raw material, substances which may inhibit the germination of seeds, the root growth or development of plants.…”

Antibody fragments: Prolonging circulation half-life special issue-antibody research

“…Antibody engineering is expanding to include non-endogenous molecular structures [6]. Many antibody derived scaffolds are in clinical trials, such as over six scFv's [7]. Additionally the functionality of monoclonal antibodies is being expanded, for example there are over 14 antibody drug conjugates (ADCs) that have been evaluated in the clinic [8].…”