Featured image: A change is coming? Image source: Amman Wahab Nizamani [CC BY-SA 4.0 (https://creativecommons.org/licenses/by-sa/4.0)], from Wikimedia Commons
We spoke in some length about why toxicology needs to change. There are several problems with the way we test for toxicity currently, including our use of animals and archaic methods. Thus, the scientists who wrote the famous Toxicity Testing in the 21st Century: A Vision and a Strategy report had the opportunity to advocate for a new and better toxicology.
Let’s look at their options and recommendations, plus the technologies that have to be used and challenges that have to be overcome, to move toxicology into the 21st century.
Options
The scientists in the committee that wrote the report considered four ways/options via which a chemical’s toxicity could be tested:
*Chemicals can be filtered prior to expansive testing. For example, if a particular chemical structure is associated with high toxicity in humans, then the chemical will not be manufactured. This avoids full-on testing and subsequent rejection of the chemical.
Recommendations
The committee mainly went with Option 4, and a bit of Option 3. They embraced the 3Rs, which is replacing, reducing and refining the use of animals in experiments. But they believed that some studies could be done on animals to understand how chemicals act and move within bodies. Currently, we largely follow Options 1 & 2. The committee has therefore suggested a fundamental shift in how we perform our toxicological studies.
Thee committee also strongly advocated a) testing a range of doses, b) looking for cellular changes (rather than whole body effects), c) studying multiple endpoints, d) assessing risks of chemical mixtures (rather than single chemical), e) testing different life stages, f) incorporating human variability (including genetic variation, preexisting health conditions, and background chemical exposures) and g) generating mechanistic information. The goal is to efficiently and quickly study the effects of multiple chemicals on human health.
Technologies
There are some really cool technologies that can be used to fulfill the committee’s grand vision. To do them justice, I will cover them in separate posts. The technologies involve using powerful computer programs, putting human organs on chips, studying small molecules, analyzing multiple cell pathways in humans, creating virtual patients, etc.
Challenges
So far, so good right? But there are some big challenges to implementing Tox21 effectively. I have described three major ones here:
- To replace animals and overcome shortcomings in our current methods, we need to design new methods to test the safety of chemicals. But how do we verify the accuracy of these methods? Especially given that our current methods unreliably predict human toxicity.
- Since Tox21 calls for measuring how a cell’s response changes due to a chemical, we need to decide what is a relevant toxic effect (as all changes will not be harmful or lasting). This will depend on how much our instruments can detect, the background noise, false alarms, etc.
- Regulators are people who look at the data on a chemical and decide what to do with it. That is, should the chemical be banned or restricted? Or is it safe to use? Currently, there are guidelines to decide this (example). These guidelines will have to be changed as our testing methods and outcomes change. Also, we need to ensure that the new guidelines are accepted widely so that regulators in different countries come to similar decisions with the same set of data.
Conclusions
While the committee did a great job with spelling out a vision for toxicology, it is important to remember this:
“Vision without action is just a dream, action without vision just passes the time, and vision with action can change the world.” By Joel A. Barker.
We will next look at how this vision can be implemented.
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