October 08, 2025

On 15 January 2025, in response to a U.S. court order, the Food and Drug Administration (FDA) formally revoked the authorization for FD&C Red No. 3 (erythrosine) as a color additive in foods and ingested pharmaceuticals.

This ruling creates strict reformulation deadlines:

  • Food manufacturers must comply by 15 January 2027
  • Pharmaceutical manufacturers must comply by 18 January 2028

After these dates, products containing erythrosine will be deemed adulterated under the FD&C Act, presenting major compliance challenges across the food, beverage, and pharmaceutical industries. For companies navigating the food additive regulatory landscape, this case underscores the importance of regulatory toxicology, Delaney Clause interpretation, and risk-based safety assessments when developing or reformulating color additives.

Background: The Delaney Clause and Carcinogenicity Concerns

The Delaney Clause, enacted in 1958 under the Food Additives Amendment to the FD&C Act, prohibits FDA approval of any additive shown to induce cancer in humans or animals. A parallel color additive clause (1960) extended the same standard to dyes used in foods, drugs, and cosmetics.

Both clauses were based on the binary mid-20th century view of carcinogens:

  • Any substance causing cancer in animals = unsafe for humans
  • No safe thresholds or dose-response considerations
  • Assumption that animal carcinogenicity always applies to humans

Modern regulatory science has evolved to assess risk (hazard × potency × exposure). However, due to the strict hazard-based language of the Delaney Clause, courts continue to enforce bans even when toxicological evidence shows negligible human relevance.

Why FD&C Red No. 3 (Erythrosine) Was Banned

Erythrosine (FD&C Red No. 3) is a synthetic xanthene dye historically permitted in U.S. foods and ingested pharmaceuticals and still authorized in Canada and the European Union. The ban stems from a 2022 color additive petition, citing studies where male rats exposed to extremely high doses (~107,000× estimated human intake) developed benign thyroid tumors.

Key points:

  • Tumors occurred only in male rats, not females or other species
  • Mode of action was hormonal, not genotoxic
  • FDA itself acknowledged: “there is no evidence FD&C Red No. 3 causes cancer in humans” (FDA, 2025b)

Despite this, the court ruled the FDA is legally bound by the Delaney Clause and must revoke erythrosine’s authorization.

Toxicological Data: What the Studies Show

Long-term rodent studies (Borzelleca et al., 1987; Capen, 2001) found:

  • Male rats on diets containing 4% erythrosine (2,464 mg/kg/day) developed thyroid follicular adenomas
  • No tumors in female rats, mice, or gerbils
  • No genotoxicity evidence

Mechanistic research confirms erythrosine acts through thyroid hormone disruption:

  • Inhibits 5'-monodeiodinase in liver
  • Reduces T4 → T3 conversion
  • Decreases circulating T3, weakening feedback control
  • Increases thyroid-stimulating hormone (TSH)
  • Chronic TSH elevation → thyroid follicular proliferation → tumors (male rats only at very high doses)

This pathway is well documented in rodents, but not relevant to human physiology.

Human Relevance: Why Rat Tumors Don’t Translate

Rodents, especially male rats, are uniquely sensitive to thyroid disruption due to:

  • Smaller thyroid hormone reserves
  • Shorter T4 half-life (12–24h vs. 5–9 days in humans)
  • Lack of thyroxine-binding globulin (TBG)
  • Baseline TSH levels up to 120× higher than humans

In humans, chronic TSH elevation generally results in goiter, not thyroid carcinoma. Decades of data confirm erythrosine tumors are rodent-specific and not predictive of human cancer risk.

Regulatory Implications of the 2025 Court Ruling

This ruling demonstrates the conflict between hazard-based law and risk-based science:

  • FDA acknowledges erythrosine is safe for humans
  • Courts ruled FDA must enforce the Delaney Clause literally
  • Future petitions and additives may face similar hazard-driven challenges

For manufacturers, this means:

  • Reformulation planning is urgent to meet 2027/2028 deadlines
  • Premarket petitions for new colorants will be scrutinized more strictly
  • Alternative color additives (natural and synthetic) will see higher demand and regulatory review

How Maven Regulatory Solutions Can Help

At Maven Regulatory Solutions, we provide expert support to help companies navigate the complex world of FDA food additive and color additive compliance. Our services include:

  • Regulatory compliance strategy for FDA color additive approvals
  • Preparation of premarket petitions supported by toxicology data
  • Risk assessment and mechanistic evaluation using modern regulatory toxicology frameworks
  • Global regulatory alignment across FDA, EFSA, and Health Canada requirements
  • Reformulation support for food, beverage, and pharmaceutical companies facing the erythrosine ban

With deadlines fast approaching, Maven can help you evaluate alternatives, mitigate regulatory risks, and prepare strong submissions that meet FDA expectations.

Key Takeaway

The FDA’s 2025 erythrosine ban is more than a single-dye decision—it’s a reminder that hazard-based legal frameworks still shape U.S. regulatory outcomes. Even where modern science shows negligible human health risk, the Delaney Clause remains binding. For industry, this highlights the need for proactive regulatory strategy, robust toxicology dossiers, and reformulation readiness.

???? Partner with Maven Regulatory Solutions to safeguard your product portfolio, navigate FDA compliance with confidence, and bring new color additives to market successfully.