The discipline of evidence-based toxicology strives to transparently, consistently, and objectively assess available scientific evidence in order to answer questions in toxicology,[11] the study of the adverse effects of chemical, physical, or biological agents on living organisms and the environment, including the prevention and amelioration of such effects.[12] Evidence-based toxicology has the potential to address concerns in the toxicological community about the limitations of current approaches to assessing the state of the science.[13][14] These include concerns related to transparency in decision making, synthesis of different types of evidence, and the assessment of bias and credibility.[15][16][17] Evidence-based toxicology has its roots in the larger movement towards evidence-based practices.

 

The classic experimental tool of toxicology is testing on non-human animals.[8] Example of model organisms are Galleria mellonella, [19] which can replace small mammals, and Zebrafish, which allow for the study of toxicology in a lower order vertebrate in vivo.[20][21] As of 2014, such animal testing provides information that is not available by other means about how substances function in a living organism.[22] The use of non-human animals for toxicology testing is opposed by some organisations for reasons of animal welfare, and it has been restricted or banned under some circumstances in certain regions, such as the testing of cosmetics in the European Union.

Since the late 1950s, the field of toxicology has sought to reduce or eliminate animal testing under the rubric of "Three Rs" - reduce the number of experiments with animals to the minimum necessary; refine experiments to cause less suffering, and replace in vivo experiments with other types, or use more simple forms of life when possible.[25][26]

In 2007 the American NGO National Academy of Sciences published a report called "Toxicity Testing in the 21st Century: A Vision and a Strategy" which opened with a statement: "Change often involves a pivotal event that builds on previous history and opens the door to a new era. Pivotal events in science include the discovery of penicillin, the elucidation of the DNA double helix, and the development of computers. ...Toxicity testing is approaching such a scientific pivot point. It is poised to take advantage of the revolutions in biology and biotechnology. Advances in toxicogenomics, bioinformatics, systems biology, epigenetics, and computational toxicology could transform toxicity testing from a system based on whole-animal testing to one founded primarily on in vitro methods that evaluate changes in biologic processes using cells, cell lines, or cellular components, preferably of human origin."[28] As of 2014 that vision was still unrealized.[22][29]

 

The United States Environmental Protection Agency studied 1,065 chemical and drug substances in their ToxCast program (part of the CompTox Chemicals Dashboard) using in silica modelling and a human pluripotent stem cell-based assay to predict in vivo developmental intoxicants based on changes in cellular metabolism following chemical exposure. Major findings from the analysis of this ToxCast_STM dataset published in 2020 include: (1) 19% of 1065 chemicals yielded a prediction of developmental toxicity, (2) assay performance reached 79%–82% accuracy with high specificity (> 84%) but modest sensitivity (< 67%) when compared with in vivo animal models of human prenatal developmental toxicity, (3) sensitivity improved as more stringent weights of evidence requirements were applied to the animal studies, and (4) statistical analysis of the most potent chemical hits on specific biochemical targets in ToxCast revealed positive and negative associations with the STM response, providing insights into the mechanistic underpinnings of the targeted endpoint and its biological domain.

Last Updated on: Nov 27, 2024