Bioavailability and pharmacokinetics of arsenic are influenced by the presence of cadmium.

Mine wastes contain a mixture of metals and metalloids including arsenic (As) and cadmium (Cd). This study investigated the potential interaction between As and Cd in a rat model. Sprague Dawley rats were dosed with sodium arsenate via the oral (0, 0.5, 5 and 15 mg As kg(-1) b.w.) or intravenous (0.5 mg As kg(-1) b.w.) route to establish its dose-response relationship in terms of bioavailability and pharmacokinetic parameters. Bioavailability of As reduced when the dose of As increased. For the interaction study a fixed oral dose of As at 2.5 mg As kg(-1) b.w. solo and in combination with Cd as cadmium chloride at 3 or 6 mg Cd kg(-1) b.w. were administered to rats. Bioavailability of As was decreased by 34-35% in the presence of Cd. Elimination half-life of As was also decreased from 69 days in the As solo group to 13-22 days in the presence of 3 and 6 mg Cd kg(-1) b.w. respectively. Decreased urinary excretion of As and tissue accumulation were also observed. A probable explanation for these findings is that As co-administration with Cd could have resulted in the formation of less soluble cadmium-arsenic complexes in the guts of the rats. Nevertheless, such an interaction between As and Cd could only explained about 44-48% of the variation when mine waste materials containing both of these elements were administered to rats. This suggests other physical properties and chemical compound formation could contribute to the observed bioavailability of arsenic in complex environmental samples.

Interaction effects of lead on bioavailability and pharmacokinetics of arsenic in the rat.

Arsenic (As) and lead (Pb) are common contaminants found in mine waste materials. For an evidence-based risk assessment, it is important to better understand the potential interaction of mixed contaminants; and this interaction study was investigated in an in vivo rat model. Following co-administration of a fixed dose of As(V) as in sodium arsenate and different doses of Pb as lead acetate to Sprague-Dawley rats, blood arsenic concentration and bioavailability decreased. A decrease in As blood concentration when lead was co-administered was observed with increasing lead doses. Pharmacokinetic parameters for As in the blood showed faster absorption and elimination of this metalloid in the presence of Pb. The elimination half-life of As decreased from 67 days in As solo group to 27-30 with doses of Pb. Bioavailability of As was also decreased by 30-43 % in the presence of Pb. Decreased urinary excretion of Pb and tissue accumulation were also observed. It indicates lower absorption of As when co-administered with Pb. A probable explanation for these findings is that As co-administration with Pb could have resulted in the formation of less soluble lead arsenate. However, such an interaction between As and Pb could only explain about one-third of the variation when real mine waste materials containing both of these elements were administered to rats. This suggests that other effects from physical and chemical parameters could contribute to the bioavailability of arsenic in complex real environmental samples.

Consistent chemical form of Cd in liver and kidney tissues in rats dosed with a range of Cd treatments: XAS of intact tissues.

X-ray absorption spectroscopy of frozen intact tissues shows that in rats exposed to a range of treatments involving cadmium, alone or in combination with other metal ions, the coordination environment of cadmium is consistent in both the liver and kidney. Comparison of the spectra from the rat tissues to biologically relevant model compounds indicates that the vast majority of the cadmium is bound to metallothionein in these tissues.