“Red Dye No. 3: The Controversial Cancer-Causing Colorant Banned by FDA”

The Food and Drug Administration announced on Wednesday that the commonly criticized red dye No. 3 will be prohibited in the United States as it has been evidenced to induce cancer in animals.

The resolution, applauded by advocacy organizations for consumers, emerges a full 25 years after researchers at the agency concluded that rats given large quantities of the synthetic color additive were significantly more prone to develop malignant thyroid tumors compared to those that were not administered the dye. Additionally, they exhibited a heightened rate of benign tumors and growths that may lead to cancer.

These observations prompted the FDA to proclaim in 1990 that red dye No. 3 could not be utilized in cosmetics or medications applied to the skin. The rationale behind this choice was evident: A federal statute known as the Delaney clause stipulates that no color additive can be deemed safe if it has been demonstrated to cause cancer in animals or humans.

Despite this, the dye continued to be an authorized food colorant. It’s present in the vibrant red cherries that enhance a bowl of Del Monte’s fruit cocktail. It gives Nesquik’s strawberry milk an appealing pink hue. Moreover, it colors beef jerky, fruit rolls, candy, ice cream and numerous additional processed goods.

Now, food manufacturers will have a period of two years to reformulate their products to exclude red dye No. 3. Meanwhile, pharmaceutical companies are granted a three-year timeframe to eliminate it from their medicinal offerings.

The FDA does not appear to be concerned that this carcinogenic substance will remain in the food supply. The agency’s standpoint suggests that the biological mechanism through which the dye induces cancer in rats does not take place in humans.

“We don’t perceive any risk to humans,” Jim Jones, the FDA’s deputy commissioner for human foods, informed Congress members last month.

In revealing the prohibition, the agency also asserted that people consume red dye No. 3 at significantly lower levels than those demonstrated to cause cancer in two studies involving rats. A plethora of additional studies in both animals and humans failed to indicate that the dye is carcinogenic.

Nevertheless, regulators revoked the approval of red dye No. 3 to respond to a petition that demanded enforcement of the Delaney clause.

“Regardless of the factual basis behind their argument, it holds no significance,” said Jensen N. Jose, regulatory attorney for food chemical safety at the Center for Science in the Public Interest, the organization that led the initiative. “Once it is established that it causes cancer, the FDA is legally obliged to ban the chemical.”

This was not the initial occurrence of the FDA prohibiting a food additive it regards as safe, in order to comply with the Delaney clause. Experts in food safety argue that this highlights the need for a refresh of the federal law.

“Many people believe we must reform this,” said Diana Winters, deputy director of the Resnick Center for Food Law and Policy at UCLA Law. “It results in some ridiculous outcomes.”

The Delaney clause forms part of a federal law enacted in 1958 that expanded the FDA’s regulatory powers over emerging food additives developed during World War II that started entering consumer items, Winters noted.

At that time, congressional members were concerned about the cancer hazards posed by various synthetic substances. Even minimal quantities seemed capable of inducing cancerous growths if they were encountered repeatedly.

Arthur Flemming, who served as Cabinet secretary for health and welfare under President Eisenhower, addressed Congress during that period,there was no possibility for FDA officials to determine if any exposure level was sufficiently low to be genuinely safe. Taking into account the numerous cancer dangers present in the environment, he remarked that the government ought to “do everything within its power to ensure individuals are not unnecessarily introducing residues of carcinogens into their diet.”

The matter was personal for Rep. James Delaney, a Democrat from New York City whose spouse was undergoing cancer treatment at the time. He ensured that the new legislation contained a zero-tolerance clause for substances that could cause cancer, although it made no mention of additives that might lead to other health complications.

“No additive shall be regarded as safe if it is found to induce cancer when ingested by humans or animals, or if it is determined, following appropriate tests for evaluating the safety of food additives, to induce cancer in humans or animals,” the Delaney clause asserts. A 1960 amendment governing color additives broadened the regulation to include dyes.

As time passed, advancements in toxicology enabled researchers to enlarge the inventory of recognized carcinogenic compounds and to detect them in increasingly smaller concentrations. Regulators were no longer as uninformed as they had been in Flemming’s era.

In 1986, the FDA aimed to consider that advancement as it assessed the safety of two color additives — orange dye No. 17 and red dye No. 19 — for application in lipsticks, nail polishes, face powders, and other cosmetics. The agency conceded that both dyes were capable of inducing cancer in laboratory animals. However, it contended that the regulatory verdict should not be dictated by a literal interpretation of an antiquated law but by the actual risks to individuals.

When those color additives were utilized as designed, those risks were extremely minimal: A panel of experts from the U.S. Public Health Service determined the lifetime cancer risk associated with the red dye was 1 in 9 million at the highest; for the orange dye, it was 1 in 19 billion. In both instances, the risk of developing cancer was “so inconsequential as to be effectively no risk,” the panel concluded.

A federal appeals court concurred that the dyes appeared to be safe. In fact, the dangers they presented were millions of times lower than those associated with smoking, the judges noted.

Furthermore, the judges highlighted, prohibiting the use of substances that carry a negligible risk of cancer might drive manufacturers to employ compounds that are more toxic, though in non-cancerous manners. Such substitutions would be “a clear setback for safety,” they declared.

Nonetheless, none of that mattered, the court ruled: If a dye or any other chemical is discovered to induce cancer in animals, the FDA’s only recourse under the Delaney clause was to ban its use.

Regulators encountered a more ludicrous circumstance in 2018 when they were requested to withdraw their approval of a flavoring additive known as myrcene.

When the synthetic substance was administered to rats at doses of 1 gram per kilogram of body weight over the course of two years, the animals developed kidney cancer and various forms of renal illness. Female mice subjected to the same treatment also developed liver cancer, the FDA stated.

However, the quantity of synthetic myrcene ingested by an average American is 813,000 times lower — approximately 1.23 micrograms per kilogram of body weight, as per the agency.

Additionally, myrcene is a natural component found in mangoes, citrus juices, cardamom, and herbs such as basil, parsley, and wild thyme. The level of natural myrcene in the food supply is around 16,500 times greater than its synthetic variant, the agency further noted.

Yet, the FDA declared the additive unsafe “as a matter of law” while assuring the public that no one’s health was actually at risk when synthetic myrcene was available in the market. It attributed the confusion to the Delaney clause.

In 2020, a cohort of scientists from the food industry remarked that the issue extends far beyond mere confusion. Annulment of approval for artificial myrcene “has contributed to the continuous decline of trust in regulatory bodies,” they contended in the journal Regulatory Toxicology and Pharmacology. Such decisions foster an unfounded fear of chemicals and lead consumers to lose confidence in the safety of the U.S. food supply, they claimed.

Red dye No. 3 received approval for use in U.S. food in 1907, at which time it was recognized as erythrosine. It gained permanent status as an authorized color additive for foods, supplements, and medications under the designation FD&C Red No. 3 in 1969.

Shortly after that determination, an industry organization known as the Toilet Goods Association petitioned the FDA to elevate the dye’s classification for cosmetics and topical medicines from provisional to permanent. The request initiated further tests in the 1970s and ‘80s, including two long-term feeding trials in rats.

From before birth and throughout their lives, the animals were given diets that consisted of the red dye at concentrations of 0.1%, 0.5%, 1% or 4%. In comparison to male rats that did not consume any dye, those that ingested the highest amounts exhibited a significantly higher rate of tumors — both malignant and benign — as well as abnormal cell growth in the thyroid. No other group demonstrated an increase in incidence substantial enough to be deemed statistically significant. Among female rats, the occurrence of benign tumors was heightened for those on the 1% diet, but not for rats on the 4% diet, contrary to what would be expected if the dye were the causative factor of cancer in these animals.

After consulting with scholars from the National Toxicology Program and the U.S. Public Health Service, the FDA reached the conclusion that red dye No. 3 could lead to cancer in animals. In 1990, the agency rejected the industry group’s appeal for permanent status.

This conclusion pertained solely to cosmeticsand topical pharmaceuticals, which had no direct impact on food items available in the U.S. At that juncture, the dye had been consistently classified as an acceptable food additive for numerous years. The findings from those rodent experiments did not suggest to the agency that its classification warranted alteration.

Throughout the years, the dye has undergone examination in mice, rats, gerbils, pigs, beagles, and humans. An in-depth assessment carried out by the World Health Organization alongside the Food and Agriculture Organization of the United Nations concluded “no issues” regarding the dye’s potential to induce cancer, hinder fertility or result in developmental complications in individuals of any age when ingested in typical quantities.

“Assertions that the inclusion of FD&C Red No. 3 in food and ingested pharmaceuticals endangers individuals are not substantiated by the current scientific data,” the agency stated on Wednesday.

Reconciling the Delaney clause’s stringent legal stipulations with progress in cancer research has consistently posed challenges for the agency, officials mentioned.

“Each time we prohibit something, it leads to legal actions,” Dr. Robert Califf, the FDA commissioner, informed the Senate Health, Education, Labor and Pensions committee last month. “If we lack scientific backing that can withstand legal scrutiny, we will not prevail in court.”

The complex regulatory procedure required to eliminate an additive from the food supply can indeed lead to litigation, stated Emily Broad Leib, the director of the Center for Health Law and Policy Innovation at Harvard Law School.

“The Delaney clause is likely more effective at first if you’re aiming to introduce a new substance into food,” she explained. “Once something is incorporated in food, it requires a considerable amount of time to remove it.”

According to some perspectives, the concern regarding the Delaney clause lies not in its enforcement of bans on food additives that present no actual cancer danger, but rather in the fact that the law neglects other avenues through which our diet may endanger our well-being.

“There are numerous naturally occurring substances in foods that can induce cancer, and the Delaney clause doesn’t account for that,” remarked Alyson Mitchell, a food scientist at UC Davis. “It also does not address other health issues, whether they pertain to kidney ailments or ADHD or mental health disorders or hormonal imbalances.”

The General Accounting Office (now referred to as the U.S. Government Accountability Office) highlighted this matter back in 1981, when it urged Congress to modify the Delaney clause in accordance with current scientific and medical understanding. It would be logical for the legislation to apply “equally to substances that cause cancer and those that do not,” as stated by the GAO.

California has prohibited all applications of red dye No. 3 within the Golden State and banned the use of six additional dyes in food served or sold in educational institutions. Scientists who evaluated the dyes for the California Office of Environmental Health Hazard Assessment concluded that “the behavioral aspects are of greater concern” than the risk of cancer, according to Asa Bradman, an exposure assessment and epidemiology expert at UC Merced and co-author of the comprehensive state assessment.

The FDA has researched the behavioral dangers associated with color additives and has not identified “a definitive and causal relationship,” an FDA representative conveyed to The Times. Research indicates that some children with behavioral challenges, like ADHD, may be reactive to food dyes, with genetic variations that influence the body’s capacity to metabolize histamine being a probable contributor. In the eyes of the FDA, this does not imply that the dyes themselves are “neurotoxic,” reported the spokesperson.

If compelling evidence emerged indicating that a synthetic dye did not satisfy FDA safety criteria, the agency would act regardless of whether the health risks were encompassed by the Delaney clause or not, the spokesperson noted.

Mitchell, who collaborated on the California report with Bradman, mentioned that since manufacturers have been gradually eliminating red dye No. 3 for over a decade, it does not pose a significant issue for her. She is more concerned about the hyperactivity threat brought forth by red dye No. 40 due to its prevalence in processed foods, especially those eaten by children.

“I appreciate the Delaney clause because I do believe it has played an essential role in aiding to safeguard our food,” Mitchell remarked. “However, it falls short. A significant amount of this needs reassessment.”