Bioavailability of cadmium in food and water: a case study on the derivation of relative bioavailability factors for inorganics and their relevance to the reference dose.

Published studies in which rats were exposed to CdCl2 in standard chow or drinking water were analyzed to compare the relative bioavailability of cadmium from the two media. Relative bioavailability was assessed from estimates of the rate of accumulation of cadmium in kidney cortex or liver. Data were grouped into tiers based on study design and reporting of data: Tier 1, identical experimental protocols and dosage can be estimated; Tier 2, very similar or identical protocols and dosage can be estimated; Tier 3, protocols may differ and dosage can be estimated; and Tier 4, protocols may differ and dosages cannot be estimated (but concentration of cadmium in food or water is reported). Tiers were nested, such that Tier 4 contained all relevant studies; Tier 3 included data sets from Tiers 1 and 2; and Tier 2 included the data set from Tier 1. Data within Tiers 1, 2, and 3 were subjected to a linear regression analysis with dosage as the independent variable and tissue accumulation rate as the dependent variable to determine whether bioavailability of cadmium was significantly different based on medium of administration. The results of this analysis show the following: (1) In rats receiving food and drinking water ad libitum, the bioavailability of cadmium in drinking water is not significantly different (P > 0.05) from the bioavailability of cadmium in food when dosages are less than 4 mg/kg body wt/day. (2) Cadmium decreases food and water consumption; therefore, assessments of relative bioavailability should be made based on actual dosage rather than exposure levels. (3) Diet composition and status of the gastrointestinal tract are probably a more important determinant of the bioavailability of cadmium than is the exposure medium. (4) Studies of the effect of total diet composition on bioavailability of cadmium may be more relevant than are studies of the effect of the exposure medium. It is concluded from this analysis that the bioavailability of cadmium in food is not different from that in water when diet is provided ad libitum. Therefore, we recommend that distinct RfDs for cadmium in food and drinking water should not be based on the assumption that the bioavailability of cadmium in drinking water is greater than that of cadmium in food.