Cadmium (Cd) is a naturally occurring chemical element that is normally present in our bodies at low concentrations. Most of the Cd that we take in each day is delivered in food. With the exception of smokers and occupationally exposed groups, food usually accounts for over 90 percent of the Cd absorbed by members of the general population.
Cd is both non-essential and highly toxic in mammals. At a biochemical level it appears that we could live without Cd, if that were possible to arrange. The high toxicity of Cd refers to its capacity as an effective poison at low dose. Exposure to a sufficient dose of Cd over a short time period is capable of causing acute poisoning with or without subsequent fatality. The acute lethal dose to humans can be as little as 0.35 grams by ingestion. Death from this cause is not rapid, occurring between 24 hours to two weeks later. However, food safety risks of Cd are in another category entirely. Here doses are measured in millionths of a gram per day, and the risks are not immediate but rather relate to the long-term consequence of cumulative exposure.
Cd is one of the best examples that we have of a biologically cumulative substance. With food as a constant daily source, and loss of each daily dose taking between 20 to 40 years, the amount of Cd retained in a person’s body gradually increases with age, from an estimated 1 millionth of a gram at birth to perhaps 15 to 80 milligrams (mg) by age 50, depending on personal history. About half (47 percent) of this accumulated Cd is retained in the liver and kidneys due to the presence of a metal-binding protein called metallothionein; a further three percent is shared between the lungs and pancreas, and the remaining 50 percent becomes more or less evenly distributed among the other tissues.
Unsurprisingly, the first reliable toxic effect of Cd accumulation in the body is the point where the burden of Cd in kidneys is sufficient to induce a change in kidney function. This toxicological endpoint is the focus of tolerable intake limits promulgated by the World Health Organization (0.025 mg of Cd per kilogram (kg) of body weight per month), and its science advisory body European Food Safety Authority (EFSA) (equivalent to 0.0108 mg/kg of body weight/month). The limits essentially represent the point at which the earliest onset of a change in kidney function may be starting to occur in post-50 year olds.
For contaminants that do not primarily act as carcinogens, regulatory bodies set tolerable intake limits by first determining the most sensitive toxicological consequence and then working backwards. It is unclear whether Cd should be treated in this way because some evidence exists that Cd may increase rates of breast and testicular cancers. The kidney is currently regarded the primary target organ of Cd toxicity with tolerable intake limits based on changes to kidney function, but a future change in approach may result in still lower recommended limits.
Another, much harder, problem exists that is likely to prevent tolerable intake limits from being reduced any further than the EFSA-recommended current figure. This is that at ordinary levels of Cd in foods, we are already hitting against the kidney-function threshold. The preferred toxicological approach for residues and contaminants in the diet is to apply an uncertainty (“safety”) factor to the lowest observed effects level to allow for inter-species and individual human variability, of perhaps 100. For Cd there is no such safety factor: The first onset of apparently toxic effects does appear to occur at the upper end of the usual intake range.