SETTING STANDARDS FOR CADMIUM: HOW AND FOR WHOM?
M. Gochfeld
Environmental and Occupational Health Sciences Institute, Piscataway, New Jersey 08854, USA

Results of the first Environmental Cadmium Workshop produced a discrepancy in the estimates of a No-observed adverse effect level (NOAEL) for cadmium, contingent on whether low-level proteinuria is reversible or constitutes a significant public health endpoint. Since 2000, no new studies have emerged to clarify this issue. Hopefully, longer term follow-up of cohorts currently under study will clarify this issue. This paper explores the approaches used by the U.S. Environmental Protection Agency (RfD), the Agency for Toxic Substances and Disease Registry (MRL) , and the European Union to estimate "safe levels" of cadmium intake (PTWI). Because of the abundance of cadmium data these values can be based on chronic human exposure studies. Although cadmium is a carcinogen by inhalation, it is not known to be a carcinogen by ingestion, although this is suspected for prostate cancer. The slope factor for cadmium would place exposure an order of magnitude lower than for non-cancer endpoints, for which the kidney is agreed to be the target. Urinary cadmium is correlated with kidney cadmium, which in turn is correlated, non-linearly, with kidney damage as measured by proteinuria. Several proteins have been studied, but beta-2-microglobulin is most frequently measured. In the general population, proteinuria can occur at a Cd-U level of 5 ugCd/g creatinine, with some studies showing elevations as low as 2.5 ug/g creatinine. In occupational studies, moderate proteinuria occurs above 10 ug/g creatinine, and often irreversible tubular damage can be seen with levels above 20 ug/g creatinine. However, the effective dose to the kidney has not been measured directly. Both glomerular and tubular damage occur, although tubular effects are most often assessed. The current allowable daily intakes on the order of 0.1 to 1.0 ug/kg/day are consistent with existing data.