Toxicology, rinsing out the poison chalice

Until the industrial revolution almost the complete gamut of poisons and toxins lay in the natural realm. Lethal alkaloids from toxic plants, arsenic-containing rocks, noxious fumes from fires and plenty of other sources of risk. It wasn’t until the Industrial Revolution and the maturation of alchemy to chemistry, that synthetic chemicals became an issue. In the 19th and 20th century, chemists identified literally tens of millions more chemicals in nature and in their laboratories and turned what was essentially a world of arsenic and old lace into the vast chemical space of toxicity we know, but cannot comprehend fully today.

According to Thomas Hartung of the Center for Alternatives to Animal Testing at Johns Hopkins Bloomberg School of Public Health, in Baltimore, Maryland, USA and also of the University of Konstanz, Germany, toxicology as a science has not evolved to keep pace with the chemical revolution. Writing in the International Journal of Risk Assessment and Management, Hartung highlights ten problems that must be addressed if toxicology is to be dragged kicking and screaming into the twenty-first century, albeit almost two decades late. These are the ten reasons toxicology has to change:

1. because we treat different substances very differently depending on product category or geographic region, while we treat substances the same, which have very different uses
2. because throughput and costs of current testing cannot satisfy the societal testing needs and do not allow early assessments in product development and design guidance
3. because predictivity for humans (and even of different animal species) is limited
4. because precautionary approaches from drug development adapted to other areas produce too many false-positives
5. because animal use is seen more and more critically by a general public, thus affecting legislation
6. because new products (biological, cell therapies, genetically modified and functional food (nutraceuticals), medical countermeasures to biological and chemical terrorism and warfare agents, as well as medical devices and nanoparticles) are not always suitable for traditional tests
7. because new and emerging hazards (e.g., endocrine effects, childhood effects such as asthma and behavioural issues, obesity, and cardiovascular effects) are not adequately covered
8. because mixture effects of toxicants cannot be adequately addressed
9. because individual susceptibilities and vulnerable subpopulations cannot yet be covered
10. because science in general has to raise research and publication standards

Hartung concedes that it is relatively easy to criticise and yet the issues seem obvious in his analysis and that change is needed. He suggests that given the intransigence in the world of international toxicological policies and methods this overarching issue must be overcome first before these ten issues can be addressed. “While current approaches are still needed, there is room for substantial change,” he says. “To meet the challenges of the 21st century, revolution rather than evolution is required.”

Hartung, T. (2017) ‘Evolution of toxicological science: the need for change’, Int. J. Risk Assessment and Management, Vol. 20, Nos. 1/2/3, pp.21–45.