A couple of weeks ago, a California resident filed a class action lawsuit against Mars, Inc., the maker of Skittles. The plaintiff alleges that Skittles “are unfit for human consumption because they contain titanium dioxide.” The plaintiff alleges that titanium dioxide is a “known toxin.” Well, as a toxicologist, I can tell you, it’s not quite that simple.
I took a look at the plaintiff’s lawsuit and the articles relied on by the plaintiff, and then went to work to use the data from the articles to assess the risk. Based on my calculations, an adult would have to eat 4,080 skittles – each and every day – for over 9 years – to achieve the genotoxic dose in someone’s spleen, the organ where titanium dioxide resides the longest, in order to see DNA damage. That would be more than 5 family size bags of skittles ingested every single day. It would cost someone over $13,700 every year in just skittles. If titanium dioxide actually caused DNA damage, which the evidence suggests it does not, based on the calories alone, that person would have bigger issues than DNA damage.
But, I’m making a really large assumption. Those calculations are based on nanosized titanium dioxide — which is not the same as the titanium dioxide used in food. Why am I making this assumption? I’m using the same assumptions that the European Food Safety Authority and the European Commission used.
Wait, Based on Your Calculations, How Can There Be A Lawsuit?
The plaintiff relies in large part on the European Commission’s ban on the use of titanium dioxide in food products to make his conclusion that titanium dioxide is a “known toxin.” The problem here is the fact that the European Commission and the United States differ on how we regulate chemicals, including food ingredients. The European Commission typically relies on a hazard-based policy and the precautionary principle. What this means is that if a chemical appears to be associated with a toxicity, even at doses that are higher than typical human exposures, they will tend to err on the side of precaution, and either limit its use, or ban it.
In the United States our regulations are based on a risk-based strategy. In toxicology, risk is a function of your exposure and the dose-response relationship between exposure and toxicity. What this means is that our regulators compare the amount of chemical you will be exposed to against the amount of chemical required to cause toxicity. They will also add in margins or uncertainty factors to decrease the allowed exposure to ensure the allowed or tolerated exposure level is safe.
Isn’t Exposure The Real Issue Because All Chemicals Are Toxic at Some Level, Right?
The fundamental law of toxicology is that all chemicals, even water, are toxic, at the right concentration and route of exposure (e.g., ingestion, inhalation, intravenous). That is why the precautionary principle makes very little sense for chemical regulation. For instance, water is one of the top killers of children in the State of Florida – due to drowning (https://www.myflfamilies.com/childfatality/state.shtml). Very little water needs to be inhaled before it is fatal. Farmers know that cattle in the summer months can also die due to water because excessive drinking dilutes the sodium in their blood too much.
In the specific case of titanium dioxide causing DNA damage, through a process called genotoxicity, we need to first assess the quality of the science, and then look at the doses that are causing the DNA damage. One of the issues with these DNA damage assays is that DNA damage is typically reversible through a process called DNA repair. DNA damage is not really an issue for most cells in our body because those cells do not multiply to form more cells – they are mature cells. The cells typically used in these DNA damage assays are also mature cells or they are not normal for some other reason (oftentimes they are cancer cells, sometimes they are immortalized by a viral transformation). Regulatory toxicologists do not put much weight on these assays. We know that DNA damage is reversible. We do rely on these assays to understand to screen chemicals for potential to damage DNA and chromosomes, but these assays cannot tell us about any DNA repair that has or will occur in the future.
There also are other reasons to not give much credit to the claims. For example, I evaluated the studies that the EFSA identified as showing titanium dioxide causing DNA damage, and noticed that every one of these studies was flawed (I’ll update this post with links to these studies as I get them on the blog). All of the studies had analysis or study design flaws that would artificially increase the chances of the assay reporting DNA damage, even if it was not actually there. We cannot draw accurate inferences from these assays to the broader human population based on these data. In addition, every study only saw DNA damage at doses that were well beyond human exposure levels. And, the EFSA committee even used data from a highly questionable journal.
So, please pass the skittles.