Grantee Research Project Results

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: Drinking Water , Human Health , 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 K_m and V_max 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, Water, Waste, Risk Assessments, Environmental Chemistry, Contaminated Sediments, Environmental Microbiology, Hydrology, Drinking Water, other - exposure, aluminum, aluminum toxicokinetics, treatment, contaminated sediment, ecological risk assessment, water quality, water quality parameters, human exposure, metal absorption, chemical contaminants, groundwater disinfection, neurotoxicity, monitoring, exposure, drinking water contaminants, drinking water treatment, apoptosis, water treatment, human health effects, human health risk, aquifer characteristics, drinking water distribution system

Progress and Final Reports:

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.