Grantee Research Project Results
1998 Progress Report: Aluminum Toxicokinetics Oral Absorption from Drinking Water and Brain Retention
EPA Grant Number: R825357Title: Aluminum Toxicokinetics Oral Absorption from Drinking Water and Brain Retention
Investigators: Yokel, Robert A. , McNamara, Patrick J.
Current Investigators: Yokel, Robert A. , McNamara, Patrick J. , Elmore, David
Institution: University of Kentucky
Current Institution: University of Kentucky , Purdue University
EPA Project Officer: Aja, Hayley
Project Period: November 25, 1996 through November 24, 1999
Project Period Covered by this Report: November 25, 1997 through November 24, 1998
Project Amount: $346,543
RFA: Exploratory Research - Human Health (1996) RFA Text | Recipients Lists
Research Category: Human Health
Objective:
The objective is to determine if aluminum (Al) in drinking water can significantly contribute to brain Al accumulation. The proposed studies will be conducted in the rat using the isotopic tracer 26Al, which will be quantitated by accelerator mass spectrometry. There are three aims (Studies 1, 2 & 3). The first is to determine the bioavailability of Al from drinking water and the influence of water hardness (calcium carbonate equivalent) and concomitant food in the stomach on its bioavailability. The second is to determine the fraction of circulating Al that enters the brain. The third aim is to determine if the brain is a "one-way sink" for Al and if not, the rate of brain Al elimination. These projections may resolve the long standing controversy whether Al in drinking water has the potential to be a contributing factor in neurodegenerative diseases and whether further epidemiological studies of Al and Alzheimer's disease and consideration of regulation of Al in drinking water are warranted.Progress Summary:
Study 1 of this project is designed to determine the oral bioavailability of Al under conditions that model consumption of drinking water and the influence of "hard' and "soft" water and the presence of gastric contents on oral Al absorption. Fisher rats have been orally dosed with 26Al or water but no 26Al. Half of the 26Al-dosed rats were dosed when they had food in their stomach; half were dosed when their stomach was empty. Half of the animals in each of these two groups received the 26Al in soft and half in hard water. Blood was repeatedly drawn prior to 26Al dosing and several times after dosing, to be able to define the area under the 26Al concentration H time curve. We have begun, but not completed preparation of the serum samples for 26Al analysis.Studies 2 and 3 require preparation of brain for AMS analysis. Our preliminary experience, using acid digestion, and ashing at 1000E produced inconsistent results. Some batches produced an amorphous ash which was easily recovered from the crucible whereas others produced a glaze that could not be recovered. We suspected that Al phosphate was forming to produce the glaze. We were able to separate Al from P using a cation exchange resin (BioRad AG 50W-X8). We developed and validated a method using this resin to separate Al from P. This method produces an ash that is easier to remove from the crucible and has less beam current suppression. A report describing this method has been accepted for publication (Brauer et al, below).
Study 2 proposed to determine how much Al enters the brain, whether Al is eliminated from the brain, and if so, how rapidly. We dosed rats i.v. with 26Al in a matrix that models Al speciation in blood plasma, and euthanize them at selected times to enable determination of the fraction of the 26Al dosed that entered the brain, whether it was cleared from the brain, and the half-life. To determine if brain Al elimination can be accelerated, some subjects received repeated injections of the Al chelator desferrioxamine. The brains from these subjects were prepared for AMS using the method of Brauer et al and have been submitted for AMS analysis.
Future Activities:
We will complete Study 1. We will extend Study 2 with later euthanasia times if necessary to estimate brain Al elimination. This decision will be based on the results from the samples submitted for AMS analysis.Journal Articles on this Report : 1 Displayed | Download in RIS Format
| Other project views: | All 9 publications | 5 publications in selected types | All 5 journal articles |
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Brauer RD, Robertson JD, Sharma P, Yokel RA. Aluminum and phosphorus separation: application to preparation of target from brain tissue for 26Al determination by accelerator mass spectrometry. Nuclear Instruments and Methods In Physics Research, Section B--Beam Interactions with Materials and Atoms 1999;152(1):129-134. |
R825357 (1998) R825357 (Final) |
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Supplemental Keywords:
RFA, Health, Scientific Discipline, Water, Toxicology, Environmental Chemistry, Health Risk Assessment, Risk Assessments, Biochemistry, Drinking Water, ecological risk assessment, neurotoxic, public water systems, brain retention, other - exposure, contaminant transport, biomarkers, human health effects, exposure and effects, animal model, exposure, kinetics, community water system, human exposure, dietary exposure, biokentics, dietary ingestion exposures, drinking water contaminants, bioaccumulation, biomarker, drinking water system, toxicokineticsProgress and Final Reports:
Original AbstractThe 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.