Kidney effects in animal studies
The kidneys are the primary target organ in animal research. In a two-year rat study, the highest doses produced measurable changes in urinary cell excretion, which is an early marker of kidney stress. These effects were used to set the acceptable daily intake. The doses that caused this effect are far above what a person would realistically consume from salt.
A 2-year chronic rat study identified the kidney as the target organ; a NOAEL of 4.4 mg sodium ferrocyanide per kg bodyweight per day was derived from urinary cell excretion changes in male rats.
2018AnimalEFSA Panel on Food Additives and Nutrient Sources added to Food (ANS), EFSA Journal
Cyanide release at food use levels
The cyanide groups in ferrocyanide are bound tightly to iron and do not release freely under normal digestion. Animal absorption studies showed that after ferrocyanide was given orally, less than 0.06 mg of free cyanide per kg bodyweight was detected. EFSA concluded that at the level used in food, the amount of cyanide potentially released is not of concern.
Absorption studies showed less than 0.06 mg free cyanide per kg bodyweight released after oral ferrocyanide dosing; at the group ADI of 0.03 mg ferrocyanide ion per kg bodyweight per day, the potential cyanide released was not considered a safety issue.
2018AnimalEFSA Panel on Food Additives and Nutrient Sources added to Food (ANS), EFSA Journal
Group ADI and exposure margin
EFSA set a group acceptable daily intake of 0.03 mg ferrocyanide ion per kg bodyweight per day, covering sodium, potassium and calcium ferrocyanide together. Estimated real-world dietary exposure from salt was around 0.003 mg per kg bodyweight per day for children, roughly one tenth of the ADI. The panel noted that only about 13% of salt products on the market are labelled as containing ferrocyanides, so actual exposure for most people is lower still.
EFSA established a group ADI of 0.03 mg ferrocyanide ion per kg bodyweight per day; refined dietary exposure estimates for children were approximately 0.003 mg per kg bodyweight per day, giving a roughly 10-fold margin below the ADI.
2018Regulatory reviewEFSA Panel on Food Additives and Nutrient Sources added to Food (ANS), EFSA Journal
Data gaps noted by regulators
The EFSA review flagged that no reproductive toxicity studies are available and that genotoxicity data are limited to a single in vitro study, which showed effects only at very high concentrations. These gaps mean the data set supporting the ADI is narrower than for some other food additives. EFSA judged the existing evidence sufficient for the authorised levels but recorded the gaps formally.
EFSA noted the absence of reproductive toxicity studies and limited genotoxicity data (one in vitro study with effects only at high concentrations) as uncertainties in the re-evaluation.
2018Regulatory reviewEFSA Panel on Food Additives and Nutrient Sources added to Food (ANS), EFSA Journal