HUMAN HEALTH RISK ASSESSMENT OF CADMIUM
Summary of the 61^st JECFA Meeting
A.M. Tritscher
International Programme on Chemical Safety, World Health Organization, Geneva,

The Joint FAO/WHO Expert Committee on Food Additives (JECFA) evaluated cadmium at three of its previous meetings. At the fifty-fifth meeting in 2000 the Committee retained the Provisional Tolerable Weekly Intake (PTWI) of 7 µg per kg of body weight, and concluded that the prevalence of renal tubular dysfunction at various dietary intakes of cadmium serves as a reasonable basis for risk assessment. The Committee acknowledged that new information indicates that a portion of the general population may be at risk of exceeding the current PTWI, but the value was maintained due to lack of precision in the risk estimates. Additional information that would help to improve the current risk assessment include human toxicokinetic data; improved dietary consumption data; studies on the relationship between biomarkers of renal tubular dysfunction and clinical disease and mortality; influence of cadmium on calcium metabolism and osteoporosis. A number of studies have addressed these knowledge gaps and at its recent 61^st meeting (2003) the JECFA reviewed this information in order to re-evaluate cadmium, key conclusions from this meeting are summarized.
The kidney is the main target organ for chronic cadmium toxicity. In test species, chronic oral exposure to cadmium results in progressive histopathological changes in the kidney, including tubular epithelial cell damage. Renal damage can be measured by increased urinary excretion of low molecular weight proteins, glucose and amino acids, as well as by increased urinary cadmium excretion. Decreases in bone calcium and increased urinary calcium excretion have also been associated with exposure to cadmium.
In humans, a number of new epidemiological studies investigated the relationship between (mainly environmental) cadmium exposure and health effects, such as renal dysfunction, mortality, calcium/bone metabolism. A number of studies attempted to refine the dose-effect/dose-response relationship between environmental cadmium exposure and renal dysfunction, as measured via biomarkers such as urinary cadmium, urinary ß2-microglobulin and N-acetyl-ß-D-glucosaminidase (NAG). Despite inconsistencies between studies, it can be concluded that low-level environmental exposure to cadmium is associated with an increased prevalence of proximal renal tubular dysfunction. However, several issues regarding biomarkers and appropriate adjustments were identified, which still render dose-response evaluations difficult. Environmental cadmium exposure is suggested to alter calcium metabolism in bone tissue and may increase the risk of osteoporosis. However, this is difficult to evaluate becausebone metabolism is influenced by many factors, such as age, nutritional and hormonal status. The presented studies were hence considered preliminary.
New data on dietary intake, based on national studies, resulted in estimates of mean cadmium intake ranging from 0.7 to 6.3 µg/kg body weight per week. Mean dietary intakes based on WHO GEMS/Food regional diets ranges from 2.8 to 4.2 µg/kg body weight per week. These mean intake estimates constitute appr. 40 to 60% of the PTWI, indicating that high consumers may exceed the PTWI. The foods contributing most to intake include rice, wheat, starchy roots/tubers and molluscs.
Overall the Committee reaffirmed that renal tubular dysfunction is the critical health outcome and that an excess prevalence of tubular dysfunction is not expected to occur at urinary cadmium levels below 2.5 µg/g creatinine. Although some studies, using sensitive biomarkers, indicate a changes in renal functions at levels below that, there remains appreciable uncertainty about the long-term health significance of these changes. Therefore, the PTWI was maintained at 7 µg per kg of body weight.