The state of the scientific revolution in toxicology

Abstract

Though the world does not change with a change of paradigm, the scientist afterward works in a different world." Thomas S. Kuhn (1922Kuhn ( -1996, The Structure of Scientific Revolutions "A scientific truth does not triumph by convincing its opponents and making them see the light, but rather because its opponents eventually die and a new generation grows up that is familiar with it."

Application of toxicology in silico methods for prediction of acute toxicity (LD50) for Novichoks

“…This article's conversion to human toxicity followed the guidelines for animal-human dose conversion based on body surface area, i.e., rat doses were converted to human equivalent doses by dividing the rat dose by 6.2 (Nair and Jacob 2016 ; Carlsen 2019 ). Science changes in phases, experiencing anomalies that lead to a crisis and revolution, resulting in a new, immature scientific paradigm that, over time, becomes the new normal (Hartung 2021 ). Toxicology has encountered a series of such anomalies that have led to a crisis.…”

Towards the dismissal of null hypothesis/statistical significance testing in public health, public law and toxicology

“…In particular, NHST should be abandoned in favor of a considerably more articulated, comprehensive and flexible approach to data analysis and synthesis, taking into consideration the dose-response relation between exposure and toxicological or beneficial effects, the consistency across studies, the biological plausibility of the relations, and the other well-known factors encompassed in the Bradford Hill criteria 15 . This change of perspective may induce some additional complexity in the explanation, reporting and interpretation of the findings of a single study, a meta-analysis or a risk assessment, given the clear simplicity of the black and white NHST approach, but will definitely help in conveying all the relevant findings and the uncertainties embedded in the body of evidence in any assessment [20][21][22][23][24] .…”

Engagement of scientists with the public and policymakers to promote alternative methods

“…While this process ultimately found no wrongdoing and had no disciplinary consequences, the respective Nature article gained much interest. In several subsequent studies, the estimates set out in Nature and ALTEX proved largely correct, the latest with the 2020 publication of EU animal use statistics on the year 2017 showing that reproductive toxicity testing alone accounted for 7.8 million animals in that single year (Hartung and Tsatsakis, 2021). It is important to note that this high number of animals is not immediately visible in the respective EU statistics (Busquet et al, 2020) as the unborn pups (though protected by the EU legislation) are not included in the statistics, as stated only in a footnote.…”