FDA bans Red Dye No. 3 under the Delaney Clause
The US Food and Drug Administration (FDA) has revoked its authorization for the use of FD&C Red No. 3, also known as Red Dye No. 3. Issued on January 15, 2025, the ban will go into effect for food (including dietary supplements) and ingested medications on January 15, 2027, and January 18, 2028, respectively.
FDA took this action under the “Delaney Clause,” a provision of the Federal Food, Drug, and Cosmetic Act (FDCA) adopted in 1958 that prohibits the use of food and color additives found to cause cancer in humans or animals, regardless of whether cancer is only found in animals and there is no or low probability of risk to humans. This action may indicate new scrutiny for other approved color additives for which the finding of cancer risk in animal testing, but no analogous risk in humans.
Background
This most recent FDA action was in response to a 2022 petition submitted by the Center for Science in the Public Interest, which was joined by 23 other health and consumer organizations. In 2023, following similar bans in the EU, UK, Canada, Australia, New Zealand, China, and Japan, California banned Red Dye No. 3 from food, but exempted FDA-regulated drugs. Moreover, use of Red Dye No. 3 in cosmetics and externally applied drugs has been prohibited by FDA since 1990.
The FDCA authorizes FDA to regulate “color additives,” which are defined as “a dye, pigment, or other substance made by a process of synthesis or similar artifice…from a vegetable, animal, mineral, or other source,” that, “when added or applied to a food, drug, or cosmetic, or to the human body or any part thereof, is capable (alone or through reaction with [an]other substance) of imparting color thereto.”
All color additives must meet FDA’s general safety standard of “reasonable certainty of no harm.” Companies can demonstrate this by submitting petitions demonstrating that the additive is safe and suitable for its intended use, including data describing stability, physical properties, chemical composition, and any carcinogenicity risks. Furthermore, under the Delaney Clause, any color additive “shall be deemed unsafe, and shall not be listed, for any use which will or may result in ingestion” if that additive “is found by the Secretary to induce cancer when ingested by man or animal.” In its order, FDA cited one of the seminal cases interpreting the scope of the agency’s authority under the Delaney Clause, noting that the Delaney Clause is “extraordinarily rigid” and denies “FDA authority to list a dye once it found it to ‘induce cancer in…animals.’” Pub. Citizen v. Young, 831 F.2d 1108, 1122 (DC Cir. 1987).
The 2022 petition from the Center for Science in the Public Interest, et al, specifically relied on the Delaney Clause in requesting that FDA ban Red Dye No. 3, arguing that it should be banned because it “already found that this color additive causes cancer in laboratory animals” in 1990 when it banned the additive from cosmetics and externally applied drugs. The petition also cited subsequent studies, which, it claimed, confirmed that Red Dye No. 3 causes cancer in male rats. In reviewing this petition and the evidence, FDA determined that the Delaney Clause applied because some studies have shown that Red Dye No. 3 can induce thyroid tumors in male rats.
“Limited relevance to humans”
Notably, FDA also stated that the way Red Dye No. 3 “causes cancer in male rats does not occur in humans,” that “[s]tudies in other animals and in humans did not show these effects,” and that claims that Red Dye No. 3 “in food and in ingested drugs put people at risk are not supported by the available scientific information.”
Despite the “limited relevance to humans” of the animal data, FDA proceeded with the ban on Red Dye No. 3 because of the Delaney Clause’s rigid standard, and despite the fact that FDA found that the color additive meets the “reasonable certainty of no harm” standard. FDA explained that “[t]he Delaney Clause prevents us from finding its use to be safe,” “...regardless of the probability, or risk, of cancer associated with exposure to the additive or of the extent to which the experimental conditions of the animal study or the carcinogenic mode of action provide insight into the health effects of human consumption and use of the additive in question.”
The future of the Delaney Clause
Significant controversy has and will continue to surround FDA’s implementation of the Delaney Clause, as evidenced by the 35 years between its prohibition of the use of Red Dye No. 3 in cosmetics and externally applied medications and the recent action to revoke its use in food and ingested medications.
Similar to California’s Proposition 65, which incorporates on its list of “known” carcinogens substances that are only classified as “possibly carcinogenic” by the International Agency for Research on Cancer (IARC), the Delaney Clause fails to require that FDA consider whether there is a significant or meaningful correlation between cancer risk in animals and the actual probability of cancer risk in humans. This failure substantially lowers the bar for opponents of approved color additives. Numerous published commentaries have criticized that approach, which bars FDA from applying its risk-based “general safety standard” – a methodology employed by nearly all other regulators – and can lead to the adoption of alternative color additives that are less studied, but not necessarily safer.
As this order was issued in the last days of the Biden Administration, it is unclear whether the Trump Administration will continue down the path of increased scrutiny of food and color additives. Robert F. Kennedy, Jr., who has been nominated to serve as Secretary of the US Department of Health and Human Services, has previously publicly expressed concerns regarding chemicals in the food supply. In addition, FDA has also committed to a formal post-market assessment of chemicals in the food supply, laying out its List of Select Chemicals in the Food Supply Under FDA Review. At least one other citizen petition is pending challenging other color additives under the Delaney Clause.
Implications for food, pharmaceutical, and supplement companies
Companies that are adversely affected by FDA’s revocation of its authorization for Red Dye No. 3 may object in writing, either electronically using the Federal eRulemaking Portal for public objections, or confidentially via mail, and request a stay and a hearing. FDA has otherwise given manufacturers of food and supplements containing Red Dye No. 3 until January 15, 2027 to comply with the ban, and manufacturers of ingested medications until January 18, 2028, to remove the additive from their products.
For all companies using Red Dye No. 3 in food, dietary supplements, or ingested medications, the forced reformulation to alternatives may add costs and further complicate supply chains. For manufacturers of prescription drugs in particular, although Red Dye No. 3 is not an active ingredient subject to heightened regulatory controls, the change in formulation will require updates to regulatory documentation and may also trigger certain notifications and regulatory assessments.
Additionally, FDA’s decision to withdraw approval of Red Dye No. 3 as a color additive is likely to draw scrutiny from the plaintiff’s bar and state regulators. As with many other ingredients newly linked to adverse health effects in animals, the most significant threats are likely to come in the form of consumer class actions. With consumer class actions, the plaintiff need only claim that they would not have paid as much for the product had they known that Red Dye No. 3 was “unsafe,” even though FDA determined that the Red Dye No. 3 animal data have “limited relevance to humans.”
There is also the possibility that some consumers will claim in product liability actions that consumption of Red Dye No. 3 caused their cancer, though that is less likely for two reasons. First, hundreds, if not thousands of foods, contain Red Dye No. 3, so it is difficult to identify one product as a single cause. Second, the toxicological data is weak. FDA acknowledged that Red Dye No. 3 “is likely not genotoxic” and that “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.”
Finally, FDA’s implementation of the strict, zero-tolerance Delaney Clause standard means that any color additive found to cause any cancer in any animal is at risk of a ban, even if the scientific evidence shows that humans are not at the same risk and that the additive otherwise meets FDA safety standards. Such bans could require swift responses from impacted companies and could also spur new waves of litigation, even in cases like Red Dye No. 3, where a ban is based on rodent data and the risk to humans is unclear or untested.