Evolution of toxicological science: the need for change

Abstract

Evolution requires change but the field of toxicology has not kept pace. The top ten problems urging change are: 1) disparity of testing requirements and risk acceptance for different products and geographical areas; 2) throughput and testing costs versus testing needs; 3) limited predictivity for humans; 4) precautionary approaches from drug development adapted to other areas; 5) animal use; 6) traditional tests unsuitable for new products; 7) lack of coverage for new hazards; 8) failure to address mixtures of toxicants; 9) lack of coverage for individual susceptibilities and vulnerable subpopulations; 10) poor basic research and publication standards. The intransigence at the root of these problems is discussed with reference to current international toxicological policies and methods. For each, the limitations are reviewed with reference to key literature. While current approaches are still needed, there is room for substantial change. To meet the challenges of the 21st century, revolution rather than evolution is required.

The need for strategic development of safety sciences

“…Current regulatory procedures do not always provide this -they use too many animals, are too costly, take too long, often lead to controversial results and are not based on human risk. No need to regurgitate all the arguments here (Hartung, 2017). The extent of the deficits can be argued, as can be the overall result of our regulatory processes, but it is clear that there is room for improvement.…”

“…This has been convincing for parts of the general public, but the scientific and regulatory arena is much less impressed by this argument. We (Hoffmann and Hartung, 2006) and others (Guzelian et al, 2005) have put forward the idea to initiate … Evidence-based Toxicology (EBT). Three main areas of interest emerged (1) a systematic review of methods (similar to the review of diagnostic methods in EBM), (2) the development of tools to quantitatively combine results from different studies on the same or similar substances (analogous to meta-analyses); and (3) the objective assessment of causation of health or environmental effects.…”

Tendencia al reemplazo de animales de experimentación

“…La aplicación del principio de las 3Rs indujo a nivel internacional un cambio en el enfoque experimental para la investigación de la toxicidad de sustancias con posible impacto en la salud humana o animal, proporcionando una estrategia para minimizar el uso y el sufrimiento de los animales de experimentación, sin comprometer la calidad del trabajo científico. Una prueba de este hecho es que los experimentos con animales disminuyeron en aproximadamente dos tercios desde su punto máximo, reportado a mediados de los años setenta (Hartung, 2017).…”

Nonanimal Models for Acute Toxicity Evaluations: Applying Data-Driven Profiling and Read-Across

“…Traditional toxicology evaluations require the use of animal models for testing new compounds. However, these animal models are costly and time-consuming, and they raise ethical concerns regarding the well-being of animals (Hartung 2017). Under this paradigm, generating substantial toxicity data for a limited number of compounds could take years, and it would be financially impossible to test all the available compounds using animal testing protocols (Hartung 2016).…”