Intestinal Aluminum Absorption and Bioavailability from Representative Aluminum Species

EPA Grant Number: R829783
Title: Intestinal Aluminum Absorption and Bioavailability from Representative Aluminum Species
Investigators: Yokel, Robert A. , McNamara, Patrick J.
Institution: University of Kentucky
EPA Project Officer: Page, Angela
Project Period: July 1, 2002 through June 30, 2005 (Extended to June 30, 2006)
Project Amount: $515,720
RFA: Health Effects of Chemical Contaminants in Drinking Water (2001) RFA Text |  Recipients Lists
Research Category: Health Effects , Drinking Water , Water

Description:

The primary objectives are to characterize the rate and properties of Al flux across a cell model of intestinal absorption, the Caco-2 cell, when introduced as the Al ion, Al citrate, Al fluoride, Al hydroxide or Al maltol. The results will be used to select the compounds that will then be studied in the rat to determine the time course and oral bioavailablity of Al (and associated ligand when administered as citrate and maltol) at physiological Al doses

Approach:

The flux of Al across Caco-2 cells will be determined using vertical diffusion chambers. The apparent permeability of each Al species will be calculated. The role of Al species concentration, temperature, sodium, Na/K-ATPase, metabolic inhibition and possibly inhibitors of monocarboxylate transporters and organic anion transporting polypeptides on Al flux will be determined. The Km and Vmax of Al flux will be determined if flux is carrier mediated. The results will suggest whether intestinal Al absorption is dependent on the Al species. The results will guide selection of Al species to be studied in the rat. The oral bioavailablity of Al, dosed as 26Al, of some or all of the above tested Al species will be assessed in the rat. The time course of 26Al appearance and disappearance in rat serum will also be compared among the Al species and will be compared to the time course of 14C from the 14C-citrate and 14C-maltolate ligands co-administered with the 26Al. This study will test the hypothesis that oral Al bioavailability is independent of the Al species consumed in water. This will be conducted by oral administration of the 26Al species, with 14C-labelled associated ligand when applicable, to rats during continuous infusion of 27Al, enabling determination of oral bioavailability by comparison of the areas under the serum Al versus time curve from concurrent oral and intravenous Al administration.

Expected Results:

It is anticipated that the oral absorption of Al will not be the same for Al citrate, Al fluoride, Al hydroxide and Al maltolate. Each of these are stable Al complexes which can be expected to remain intact in the absence of competing ligands. Therefore, they should be absorbed intact unless unknown intracellular ligands can successfully compete with citrate, fluoride, hydroxide and maltolate. These studies address the relative influence of Al complexes on the distribution of aluminum and the differences among their pharmacokinetics in water.

Publications and Presentations:

Publications have been submitted on this project: View all 8 publications for this project

Journal Articles:

Journal Articles have been submitted on this project: View all 2 journal articles for this project

Supplemental Keywords:

accelerator mass spectroscopy, Caco-2 cells, decision making, drinking water, metal absorption, rat, RFA, Health, Scientific Discipline, Waste, Water, Hydrology, Contaminated Sediments, Environmental Chemistry, Risk Assessments, Environmental Microbiology, Drinking Water, ecological risk assessment, monitoring, groundwater disinfection, metal absorption, other - exposure, human health effects, water quality parameters, aquifer characteristics, exposure and effects, exposure, contaminated sediment, aluminum, chemical contaminants, neurotoxicity, human exposure, treatment, drinking water distribution system, water quality, apoptosis, drinking water contaminants, water treatment, drinking water treatment, human health risk

Progress and Final Reports:

2002 Progress Report
2003 Progress Report
2004 Progress Report
Final Report