INS 551 and INS 536 in Low-Sodium Salt - Long-Term Effects

What Are These Additives?

INS 536 - Potassium Ferrocyanide

The Cyanide Question

Regulatory Status & ADI

• JECFA/WHO (1975) and the EU Scientific Committee on Food (1990) both approved it with a group ADI of 0-0.025 mg/kg body weight per day.
• The UK Committee on Toxicity (COT, 1994) revised this to 0-0.05 mg/kg bw/day, based on a NOAEL (no observed adverse effect level) from long-term rat studies at 50 mg/kg, with a 100x safety factor applied.
• In 2018, the EFSA ANS Panel re-evaluated sodium, potassium, and calcium ferrocyanides and concluded: "Ferrocyanides (E 535-538) are of no safety concern at current authorised use and use levels."
• Maximum permitted level in salt: 20 mg/kg (individually or combined).

Potential Long-Term Concerns (Where Uncertainty Exists)

1. Nanoparticle considerations: Not directly applicable to ferrocyanides, but regulators note that long-term studies on combination additive exposure are generally limited.
2. Kidney function: At very high doses in animal models, there is some evidence of renal tubular effects - but these are far above food-use levels.
3. People with impaired kidney function: Those with chronic kidney disease (CKD) already need to be cautious with low-sodium salt in general because of the high potassium chloride content (see below), not specifically because of ferrocyanide.
4. Gap in independent research: A Chemistry Stack Exchange expert honestly noted: "Few studies have been conducted with real population samples over long durations - serious funding and population-level studies are still lacking." The safety is based on animal data + estimated exposure modeling, not long-term human cohort studies.

INS 551 - Silicon Dioxide

Function and Form

Regulatory Status

• FDA classifies it as GRAS (Generally Recognized as Safe) under 21 CFR 172.480, at levels not exceeding 2% by weight.
• EFSA re-evaluated it in 2018 and again in 2024 - concluded it does not raise a safety concern in any population group, including infants.
• No ADI was set (which means "not specified" - a positive designation, meaning no limit needed at current use levels).

Long-Term Concerns

1. Nanoparticle uncertainty: EFSA flagged that the proportion of nano-sized particles in food products is poorly characterized. Limited toxicology studies exist specifically for nano-sized fractions of amorphous silica. This remains an open area of research.
2. Systemic bioavailability: Very low - most passes through the digestive tract unchanged. Precise absorption data in humans is still limited.
3. Crystalline vs. amorphous distinction is critical: Crystalline silica (industrial exposure, inhaled) causes silicosis, kidney disease, and increased autoimmune disease risk. The food form is amorphous and ingested - these risks do not apply.
4. No adverse events reported from dietary silicon dioxide to date.

The Bigger Long-Term Concern in Low-Sodium Salt

• Hyperkalemia risk: People with CKD, diabetes, heart failure, or those on ACE inhibitors/ARBs/potassium-sparing diuretics can develop dangerous high potassium levels. This is a well-established, clinically significant risk.
• Cardiovascular benefits: For healthy individuals and hypertensive patients, the higher potassium intake from these salts actually reduces blood pressure and cardiovascular risk - a major benefit confirmed by multiple trials.

Summary