DEVELOPMENT OF A PHARMACOKINETIC MODEL FOR CHROMIUM IN THE RAT FOLLOWING SUBCHRONIC EXPOSURE .1. THE IMPORTANCE OF INCORPORATING LONG-TERM STORAGE COMPARTMENT

A pharmacokinetic model of chromium depuration in the rat has been dev eloped under subchronic exposure conditions. Rats were exposed to 100 ppm Cr(VI) in their drinking water for 6 weeks, followed by a 140-day period of depuration. Tissue concentrations of Cr at the end of the 6- week exposure period were greatest in the bone, spleen, and kidney, wi th lower concentrations present in the liver and blood. The overall ki netics of Cr depuration from the tissues were relatively slow, especia lly for the largest compartment which included bone. The results indic ated that the half-life of Cr in bone exceeded 100 days. A three-compa rtment model was developed to fit the data. Liver, kidney, and spleen were grouped into a single compartment which was linked to a major sto rage compartment (i.e., bone, skin, hair, and muscle) via the blood. U sing this model, the time to a 50% reduction of whole body Cr (i.e., l oss of total Cr mass for the whole rat) was calculated to be about 80 days. The higher half-life for the storage compartment of 100 days is due to the relative weights of the compartments and the more rapid los s of Cr from the liver, kidney, and spleen compartment. The data sugge st that Cr may be sequestered and release of Cr by the storage compart ment over an extended period of time, thereby, may play an important r ole in maintaining elevated body burdens and tissue concentrations of Cr following long-term exposure to this toxic metal. (C) 1994 Academic Press, Inc.