After mine closure people and animals can be exposed to a mixture of harmful metals and metalloids from mine waste materials. In the absence of scientific data, it is general to assume that ingested metal/metalloid is 100% bioavailable for absorption. Studies have shown that this is often not the case. A risk based approach utilising site specific bioavailability data can reduce unwarranted expensive/extensive remediation whilst still protecting public health.
However, the impact of metal/metalloid interactions on bioavailability using a mammalian system has not been well studied. This project examines the effect that metals and metalloids have on each other regarding absorption, storage and excretion using a rat model. Arsenic, copper, cadmium, lead and zinc were selected as the metals/metalloids most significant to mine tailings in Australia. Target interactions were those affecting the toxic non-essential elements of arsenic, cadmium and lead.
A solution made from a soluble salt of the metal/metalloid was dosed to each rat in a group (N=4-6 rats) as a single intravenous or oral dose. Groups were given either a single metal/metalloid or several metals/metalloids dosed sequentially to the each animal. Mixtures selected were binary combinations and one triple combination of the chosen elements. Intravenous dose rates were 1 or 2mg Cd/kg for cadmium chloride, 1mg Pb/kg for lead acetate, 0.5mg As/kg for sodium arsenate or sodium arsenite, and 2mg Zn/kg for zinc sulphate. Oral doses rates were 0.5mg As/kg for sodium arsenate or sodium arsenite, 3mg Cd/kg for cadmium chloride, 10mg Cu/kg for copper sulphate, 10 or 5mg Pb/kg for lead acetate, and 2 or 5 mg Zn/kg for zinc sulphate. After dosing, urinary metal/metalloid excretion over 10 days, and liver and kidney levels at 10 days were analysed using ICP-MS.
It was found that copper dosed alone intravenously (i.v.) or per os (p.o.) increased the background urinary arsenic excretion on average by 60%. Co-administration of 1 mg Pb/kg i.v. with 0.5mg Asv/kg i.v increased arsenic accumulation in the liver by 3% of the dose and decreased urinary arsenic excretion by 36% of the dose compared to 0.5mg Asv/kg i.v. alone. The co-administration of 1mg Cd/kg i.v. with 0.5 mg Asv/kg i.v. increased arsenic in the liver by 7% of the dose and decreased arsenic in urine by 31% of the dose. Arsenate + cadmium + lead together decreased levels of arsenic in the liver by 1% of the dose and decreased urinary arsenic excretion by 22% of the dose compared to arsenate solo i.v.. Differences were only statistically significant between arsenate and arsenate + cadmium groups and between arsenate + cadmium + lead and arsenate + lead or arsenate+ cadmium groups.
For orally dosed arsenate groups cadmium, lead, cadmium + lead, and copper co-administered with arsenate all significantly decreased the arsenate excreted in urine by 13-18% of the dose compared to arsenate solo p.o.. However compared to arsenate solo p.o., liver arsenic increased by 3% and 5% of the dose and kidney arsenic increased by 0.5% and 0.6% of the dose for arsenate + cadmium and arsenate + cadmium + lead groups respectively. Lead+ arsenate was an exception which had 1.3% and 0.2% less of the arsenic dose in the liver and kidney respectively compared to arsenate solo p.o.. Arsenite with cadmium, lead or both p.o. had higher urinary arsenic excretion (1.5-3.4% more of the As dose) and more arsenic in 1he liver (2.6-5.6% of1he dose) compared to arsenite solo p.o., though this was not statistically significant. Oral copper co-arsenic tended to decrease urinary arsenic excretion and liver arsenic with little change in kidney arsenic.
Cadmium showed a trend for increased urinary excretion and redistribution from the liver to the kidney when dosed with zinc intravenously, though differences were not significant. Arsenite and arsenate mixed with cadmium tended to increase liver cadmium accumulation in intravenously dosed groups compared to cadmium solo i.v .. Orally dosed cadmium groups showed a trend for increased cadmium in the liver and kidney with a 3mg Cd/kg and 5mg Zn/kg mixture compared to cadmium solo p.o.. No other trends were observed for cadmium in orally dosed groups.
Urinary lead excretion was decreased by co-administration of zinc i. v .. Kidney lead levels were increased with co-administration of arsenite i.v.. Liver and kidney lead levels were decreased in a lead+arsenic+cadmium mixture dosed i.v.. Oral co-administration of arsenate and cadmium with lead (5mg/kg p.o) increased lead concentrations and percentage of lead dose in the liver and kidney compared to lead solo (10mg/kg p.o.). Despite the lower lead dose rate in the mixture it appears that arsenate + cadmium increased lead in these organs. Similarly, oral administration of zinc + lead increased lead in the kidney. Lead + zinc co-administered tended to increase zinc concentrations in the liver and kidney for both i.v. and p.o. mixtures.
This project shows that metals and metalloids do interact with each other, both during absorption from the gastrointestinal tract, and in the storage and urinary excretion from the body, once absorbed. Furthermore, results suggest that urinary excretion of metals and metalloids as a measure of their bioavailability in a mixture may be erroneous, due to altered organ storage and urinary excretion when other metals/metaloids are present. Suggestions for future research are given.