Assessing Safety Without Animal Testing: The Road Ahead

Abstract

Humanity is facing unprecedented challenges in the 21st century in the forms of climate change, degradation of the natural and built environment, pandemics, and global inequality in the impacts of these stressors. Governments and industries have indicated their commitment to addressing these challenges through innovation. We are already in the midst of applying novel technologies to energy generation and distribution, transportation, vaccine and medicine development, disease vector control, raw material sourcing, and others. Each of these is dependent on its own set of chemistries, all of which need to be assessed for safety. Scientists and regulators have long relied on animal tests as the basis for identifying the hazards of chemicals and for determining the conditions under which people can be exposed without incurring risk. The animal testing paradigm has provided a solid basis for hazard and risk assessment; the vast majority of chemical regulatory standards are based on animal data and appear to be health protective. However, there are important limitations to animal testing; although the mechanisms of action of toxicants are largely equivalent between humans and lab animal models, there are differences in pharmacokinetics, metabolism, and pharmacodynamics such that the concordance between human and lab animal results is not perfect, and there are ethical issues with the continuing use of animals when alternatives are available. Furthermore, animal testing has limited capacity; it has not kept pace with regulatory needs, particularly for compliance with chemical regulatory laws like Europe’s Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH). Finally, the animal testing battery does not evaluate every possible adverse outcome (although it is probable that most potential modes of action are covered). Meanwhile, nonanimal methods have improved to the extent that they can supplement animal testing and even replace it for some toxicity endpoints. The improvements are largely attributable to advances in toxicology that have identified modes of action and interdisciplinary science that has led to biotechnology and computational power that make it possible to understand and measure chemical-biological interactions at the molecular level that underlie adverse responses. Significant advances in understanding biological responses to chemicals has led to a different approach for predicting toxicity that is more focused on the initial events leading to adverse outcomes, an approach that has been termed 21st century toxicology.

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