Excursions of intake above ADI: case study on cadmium.

High oral intake of cadmium via food or drink in a single dose by humans gives rise to vomiting, abdominal pain, and diarrhea. Concentrations of cadmium in drinks giving rise to such symptoms have been 16 mg/liter and higher corresponding to doses of 3 mg and higher. Longer term intakes of food (rice) with concentrations around 1 mg/kg corresponding to daily intakes of 600 micrograms have given rise to some less pronounced symptoms including signs of malabsorption. Reproductive and developmental effects have been observed in animal experiments at oral and other exposures. The present provisional tolerable weekly intake (PTWI) for Cd is 500 micrograms (a weekly intake of 7 micrograms/kg body wt), corresponding to a daily intake of 70 micrograms or 1 microgram per kg body wt. Recent data demonstrating renal dysfunction in humans at even lower lifelong oral exposures indicate that the PTWI needs to be lowered in the future. An estimated lowest-observed-adverse-effect level (LOAEL) for symptoms from the gastrointestinal tract in humans after intake of a single oral dose is 43 micrograms/kg body wt. If a safety factor of 3-10 is used based on LOAEL, a tolerable single dose would be 0.3-1 mg (4 to 14 micrograms/kg body wt). For longer time exposures (months-a few years) daily intakes of 200 micrograms (3 micrograms/kg body wt) may be tolerated without obvious gastrointestinal symptoms or signs. At present, there is no convincing human evidence that such doses can cause reproductive or developmental effects, but since such effects have been reported in animals, it may be advisable not to exceed a daily intake of 1 microgram/kg body wt for such potentially sensitive subsections of the population as children and women who are pregnant or lactating. Any excursions above the PTWI need to be compensated for by a corresponding period with intake below the PTWI in order for the cumulative dose to be low enough to avoid the long-term effects of cadmium on the kidney.