The FDA recently removed FD&C Red No. 3 from the list of approved food additives. This was not based on any new data or interpretation of the data, but rather was a response to a petition from food safety and environmental groups. Their argument was in turn based on the Delaney Clause, a 1960 law saying that the FDA must ban any food dyes that have been shown to cause cancer in humans or animals.
While removing a food coloring from the food supply is hardly a hill worth dying on, the underlying principles here are extremely important. Food and drug regulations are extremely complicated, and there is no one obvious optimal way to determine if a food additive is safe for humans and in what dose. Some decisions are easy, because a potential additive has clear toxicity at one end of the spectrum or no signs of toxicity at the other. But many foods and additives are somewhere in between these extremes, with conflicting and complex scientific data. Let’s take a look at the evidence for Red No. 3 to illustrate.
The petition reviewed much of the published evidence on Red No. 3 but focused on two studies in rats that showed an increased incidence of cancer. This is because the petition was specifically asking the FDA to determine if these studies trigger the Delaney Clause.
There is a deeper political issue here as well that I will not get into, but just point out. The recent Supreme Court decision ending Chevron Deference may have played a role here. The question is – who interprets federal regulations? The Chevron Deference standard says that the experts working in the relevant agency would be given deference when interpreting the law. For example, the FDA could determine how to apply the Delaney Clause based upon an expert level understanding of the complexities of toxicity research. The SC ended such deference, meaning that regulations can be interpreted by the courts without deference to experts. One has to wonder if this otherwise odd decision by the FDA was a response to this.
Let’s get back to those rat studies. These came from the “Certified Color Manufacturers’ Association (CCMA) initiated studies on FD&C Red No.3 including chronic toxicity and carcinogenicity studies in rats and mice.” In these studies the rats were fed “4% FD&C Red No.3 in the diet (2464 mg/kg/day) during life-time (30 months) following in utero exposure.” To put this exposure level in context, the Acceptable Daily Intake (ADI) for Red No. 3 based on studies in humans was set at 0.1 mg/kg/day. So the rats were fed 24,640 times as much Red No. 3 as the ADI in humans, throughout their entire lives, following in utero exposure.
Further, the hormonal mechanism by which there was an increase in thyroid cancer in these rats does not exist in humans. The evidence shows there is no mutagenicity in humans. This is why the FDA approved Red No. 3 in the first place, as have many other countries.
This is where, I think, the Chevron Deference issue comes into play. The Delaney Clause says that the FDA should ban food dyes shown to cause cancer in animals – but as experts they can interpret this to mean that the animal data is relevant to humans. But now they are facing a petition based upon a simplistic interpretation of the law without the Chevron Deference to back them up, so they caved.
The FDA announcement is dripping, in my perception, with passive aggressiveness in response to this situation. They state:
“The petition requested the agency review whether the Delaney Clause applied and cited, among other data and information, two studies that showed cancer in laboratory male rats exposed to high levels of FD&C Red No. 3 due to a rat specific hormonal mechanism. The way that FD&C Red No. 3 causes cancer in male rats does not occur in humans. Relevant exposure levels to FD&C Red No. 3 for humans are typically much lower than those that cause the effects shown in male rats. Studies in other animals and in humans did not show these effects; claims that the use of FD&C Red No. 3 in food and in ingested drugs puts people at risk are not supported by the available scientific information. “
They are basically saying, we are banning Red No. 3 despite the fact that the science says it is safe at the approved level of exposure. They point out later that Red No. 3 is not widely used in food so higher levels of exposure are unlikely.
This is a horrible precedent.
There are many technical issues here that I have discussed previously in SBM. There is a difference, for example, between hazard and risk. Hazard means there is a potential mechanism of harm, while risk is the chance of actual harm occurring at exposure levels. The FDA generally uses a risk assessment when determining approval.
Further, much toxicity research is designed to probe for possible hazard, and not determine risk. Rats are given ridiculous doses of substances to see if there is any potential mechanism of harm. This is more useful when the studies are negative – we can say that even at extremely high exposures there is no apparent negative effect. But when there is a negative effect, that does not determine that there is a risk for humans (that kind of research was never meant to determine that), but rather scientists now have a potential mechanism to further research. This further research can include whether or not the mechanism is relevant in humans.
This decision on Red No. 3 turns the relationship between toxicity research and regulations on its head. If Red No. 3 can be banned based upon exposure levels 24 thousand times greater than the highest allowed human exposure, and a mechanism that is relevant in rats but not in humans, then you can get almost anything banned.
Further, many of the groups in the petition are known to have a history of chemophobia and questionable use of science in the name of advocacy. We have handed a flame thrower to cranks and charlatans who can now burn down the regulatory order.
Food regulations are critically important for the safety of Americans, and we need an agency with the authority and expertise to apply the best and most up-to-date science to ensure the safety of our food supply. In this endeavor science should dominate over politics and ideology, but that is clearly not the world we are currently living in.