Jarup, L; Berglund, M; Elinder, CG; Nordberg, G; Vahter, M
This report provides a review of the cadmium exposure situation in Sweden and updates the information on health risk assessment according to recent studies on the health effects of cadmium. The report focuses on the health effects of low cadmium doses and the identification of high-risk groups.
The diet is the main source of cadmium exposure in the Swedish nonsmoking general population. The average daily dietary intake is about 15 mu g/day, but there are great individual variations due to differences in energy intake and dietary habits. It has been shown that a high fiber diet and a diet rich in shellfish increase the dietary cadmium intake substantially. Cadmium concentrations in agricultural soil and wheat have increased continuously during the last century. At present, soil cadmium concentrations increase by about 0.2% per year. Cadmium accumulates in the kidneys. Human kidney concentrations of cadmium have increased several fold during the last century. Cadmium in pig kidney has been shown to have increased by about 2% per year from 1984-1992. There is no tendency towards decreasing cadmium exposure among the general nonsmoking population.
The absorption of cadmium in the lungs is 10-50%, while the absorption in the gastrointestinal tract is only a few percent. Smokers have about 4-5 times higher blood cadmium concentrations (about 1.5 mu g/l), and twice as high kidney cortex cadmium concentrations (about 20-30 mu g/g wet weight) as nonsmokers. Similarly, the blood cadmium concentrations are substantially elevated in persons with low body iron stores, indicating increased gastrointestinal absorption. About 10-40% of Swedish women of child-bearing age are reported to have empty iron stores (S-ferritin <12 mu g/l). In general, women have higher concentrations of cadmium in blood, urine, and kidney than men. The population groups at highest risk are probably smokers, women with low body iron stores, and people habitually eating a diet rich in cadmium.
According to current knowledge, renal tubular damage is probably the critical health effect of cadmium exposure, both in the general population and in occupationally exposed workers. Tubular damage may develop at much lower levels than previously estimated, as shown in this report. Data from several recent reports from different countries indicate that an average urinary cadmium excretion of 2.5 mu g/g creatinine is related to an excess prevalence of renal tubular damage of 4%. An average urinary excretion of 2.5 mu g/g creatinine corresponds to an average concentration of cadmium in renal cortex of 50 mu g/g, which would be the result of long-term (decades) intake of 50 mu g per day.
When the critical concentrations for adverse effects due to cadmium accumulation are being evaluated, it is crucial to consider both the individual variation in kidney cadmium concentrations and the variations in sensitivity within the general population. Even if the population average kidney concentration is relatively low for the general population, a certain proportion will have values exceeding the concentration where renal tubular damage can occur. It can be estimated that, at the present average daily intake of cadmium in Sweden, about 1% of women with low body iron stores and smokers may experience adverse renal effects related to cadmium. If the average daily intake of cadmium would increase to 30 mu g/day, about 1% of the entire population would have cadmium-induced tubular damage. In risk groups, for example, women with low iron stores, the percentage would be higher, up to 5%.
Both human and animal studies indicate that skeletal damage (osteoporosis) may be a critical effect of cadmium exposure. We conclude, however, that the present evidence is not sufficient to permit such a conclusion for humans. We would like to stress, however, that osteoporosis is a very important public health problem worldwide, but especially in the Scandinavian countries. Studies assessing the potential role of cadmium as a risk factor for osteoporosis are already in progress. The results from these studies may lead to a reevaluation of the critical effects of cadmium exposure. It should also be noted that women have a much greater risk of developing osteoporosis. Since women are also at greater risk of achieving a high cadmium dose, they may be particularly at risk for cadmium-induced osteoporosis.
The International Agency for Research on Cancer concluded in 1993 that there was sufficient evidence to classify cadmium as a human carcinogen (category I). As the World Health Organization earlier pointed out, however, the human evidence was based on relatively few studies, including a limited number of lung cancer cases, and that the control of confounding was insufficient. Recent reevaluation of these studies, as well as new data from a Swedish cohort, indicate that a classification of cadmium as a "probable human carcinogen, group 2A" would be more appropriate. This conclusion is also in agreement with the existing classification of some cadmium compounds in EC countries in the European Union (carcinogen category 2; annex 1 to directive 67/548/EEC).
Although an increased risk for cardiovascular disease was found in a Japanese population with evidence of tubular damage, there is presently not sufficient evidence for cadmium as a risk factor for cardiovascular disease.
Studies on experimental animals have indicated that a single high dose of cadmium can give rise to necrosis of the testicles. Long-term, low-dose exposure to cadmium did not give rise to this effect, but may cause changes in male sex hormone levels in animals. Such effects have not been shown to occur in humans, but very few studies have been done on this topic. The available evidence does not allow any conclusions to be drawn about the effects on the male reproductive system at protracted low exposures.
Elevated levels of cadmium in babies of smoking mothers have been associated with decreased birthweight. Since decreased birthweight was not observed in babies of mothers occupationally exposed to cadmium, the causal relationship is uncertain. However, pathological changes have been induced in human placentas perfused with cadmium after delivery. Since experimental animal studies have shown that cadmium may give rise to several adverse effects in ovaries and placentas and also to teratogenic and developmental effects, there is a need for more studies on humans. The present human evidence is not sufficient to consider female reproductive and developmental effects as critical effects in humans.
In conclusion, recent data indicate that adverse health effects from cadmium exposure may develop in about 1% of the adult general population at an average daily intake of 30 mu g over a life-span. In high-risk groups the percentage will be even higher (up to 5%). This intake is already exceeded by some population groups in Europe, and the margin is very narrow for large groups. Therefore, measures should be taken to reduce cadmium exposure in the general population to minimize the risk of adverse health effects. At an average daily intake of 70 mu g/day [corresponding to the present PTWI (provisional tolerable weekly intake)], 7% of the adult general population would be expected to develop cadmium-induced kidney lesions. For high-risk groups the percentage would be even higher (up to 17%). Thus, in our opinion, the current PTWI is unacceptable and needs to be lowered.