Toxicokinetics of cadmium in lactating and nonlactating ewes after oral and intravenous administration

We studied the toxicokinetics of cadmium on two groups of ewes, a lactating group and a nonlactating group, after single intravenous and oral administrations of cadmium chloride using a semisimultaneous method and a three-compartment model. The nonlactating ewes showed a low cadmium bioavailability (0.12-0.22%), a large steady-state volume of distribution (23.8 +/- 5.4 liter/kg), and a low blood clearance (0.20 +/- 0.03 liter/kg/day). Their mean residence time was 113 +/- 28 days. The lactating ewes had a higher bioavailability (0.33-1.7%). Their mean residence time was close to that in nonlactating ewes despite a greater blood clearance (0.46 +/- 0.013 liter/kg/day) because the volume of distribution of cadmium in the body was larger (V-SS = 48.8 +/- 10.3 liter/kg). Their cadmium clearance in milk, changing with time, remained low and could not explain their higher blood clearance. In one nonlactating ewe, a greater cadmium bioavailability (5%) increased cadmium in the body. Increased cadmium amounts could induce renal damage and shorten the mean residence time (78 days). (C) 1997 Academic Press.