Medicine and Health Sciences Commons^™

Correction To Some Statements About Aluminum In Sulaiman Et Al., Robert A. Yokel

Pharmaceutical Sciences Faculty Publications

No abstract provided.

Aluminum Reproductive Toxicity: A Summary And Interpretation Of Scientific Reports, Robert A. Yokel

Pharmaceutical Sciences Faculty Publications

Publications addressing aluminum (Al)-induced reproductive toxicity were reviewed. Key details were compiled in summary tables. Approximate systemic Al exposure, a measure of bioavailability, was calculated for each exposure, based on the Al percentage in the dosed Al species, Al bioavailability, and absorption time course reports for the exposure route. This was limited to laboratory animal studies because no controlled-exposure human studies were found. Intended Al exposure was compared to unintended dietary Al exposure. The considerable and variable Al content of laboratory animal diets creates uncertainty about reproductive function in the absence of Al. Aluminum-induced reproductive toxicity in female mice and …

Toxic And Essential Trace Element Content Of Commonly Administered Pediatric Oral Medications, Robert A. Yokel, Sarah E. Seger, Jason M. Unrine

Pharmaceutical Sciences Faculty Publications

OBJECTIVES: The aim of this study was to test the hypothesis that commonly administered pediatric oral medications are a significant source of toxic elements. The concentrations of 16 elements were determined in 14 frequently used pediatric oral medications.

METHODS: Samples were prepared for analysis by dilution or nitric acid microwave-assisted digestion and analyzed by inductively coupled plasma mass spectrometry. The intake of each element from administration for 1 week of the medication's maximum recommended daily dose to 6-month-olds was calculated and compared to an exposure guideline for that element. Exposure guidelines used for adverse effects were minimal risk levels, oral …

Aluminum And Phthalates In Calcium Gluconate: Contribution From Glass And Plastic Packaging, Robert A. Yokel, Jason M. Unrine

Pharmaceutical Sciences Faculty Publications

Introduction: Aluminum contamination of parenteral nutrition solutions has been documented for three decades. It can result in elevated blood, bone, and whole body aluminum levels associated with neurotoxicity, reduced bone mass and mineral content, and perhaps hepatotoxicity. The primary aluminum source among parenteral nutrition components is glass-packaged calcium gluconate, in which aluminum concentration the past three decades has averaged~ 4000 [mu]g/L, compared to < 200 [mu]g/L in plastic container-packaged calcium gluconate. A concern about plastic packaging is leaching of plasticizers, including phthalates, which have the potential to cause endocrine (male reproductive system) disruption and neurotoxicity.

Methods: Aluminum was quantified in samples collected periodically over more than two years from three calcium gluconate sources used to prepare parenteral nutrition solutions; two packaged in glass (from France and the US) and one in plastic …

Flow-Through Filter To Remove Aluminum From Medical Solutions, Robert A. Yokel, Wesley R. Harris, Christopher D. Spilling, Robert Joseph Kuhn, Vasiliy Paul Abramov, Jason Matthew Lone

Pharmaceutical Sciences Faculty Patents

A flow through filter assembly includes a trivalent and tetravalent metal ion capturing agent and a flow controller providing a predetermined flow rate which allows capture of the trivalent and tetravalent metal ions by the capturing agent.

Systematic Review Of Potential Health Risks Posed By Pharmaceutical, Occupational And Consumer Exposures To Metallic And Nanoscale Aluminum, Aluminum Oxides, Aluminum Hydroxide And Its Soluble Salts, Calvin C. Willhite, Nataliya A. Karyakina, Robert A. Yokel, Nagarajkumar Yenugadhati, Thomas M. Wisniewski, Ian M. F. Arnold, Franco Momoli, Daniel Krewski

Pharmaceutical Sciences Faculty Publications

Aluminum (Al) is a ubiquitous substance encountered both naturally (as the third most abundant element) and intentionally (used in water, foods, pharmaceuticals, and vaccines); it is also present in ambient and occupational airborne particulates. Existing data underscore the importance of Al physical and chemical forms in relation to its uptake, accumulation, and systemic bioavailability. The present review represents a systematic examination of the peer-reviewed literature on the adverse health effects of Al materials published since a previous critical evaluation compiled by Krewski et al. (2007).

Challenges encountered in carrying out the present review reflected the experimental use of different physical …

A Filtration System That Greatly Reduces Aluminum In Calcium Gluconate Injection, Usp Used To Prepare Parenteral Nutrition Solutions, Robert A. Yokel, Wesley R. Harris, Christopher D. Spilling, Vasiliy P. Abramov, Jason M. Lone, Robert J. Kuhn

Pharmaceutical Sciences Faculty Publications

OBJECTIVE: The study objective was to reduce aluminum (Al) in Calcium Gluconate Injection, US Pharmacopeia (USP) used in the preparation of parenteral nutrition (PN) solutions.

METHODS: A flow-through filter containing an immobilized chelator that complexes Al from Calcium Gluconate Injection, USP as it flows through the filter was designed, refined by design modifications, and extensively tested. When a small-volume parenteral vial containing 100 mL of Calcium Gluconate Injection, USP is connected on the inlet side of the filter, and the outlet side is connected to an evacuated receiving vial, the filtered solution is drawn into the receiving vial. This constitutes …

Aluminum In Food – The Nature And Contribution Of Food Additives, Robert A. Yokel

Pharmaceutical Sciences Faculty Publications

No abstract provided.

The Pharmacokinetics And Toxicology Of Aluminum In The Brain, Robert A. Yokel

Pharmaceutical Sciences Faculty Publications

The chemical forms (species) of aluminum in blood plasma and brain extracellular fluid are considered, as they are the candidates for brain aluminum uptake and efflux. The blood-brain barrier is the primary site of brain aluminum uptake. The mechanism of brain uptake of aluminum transferrin, long thought to be mediated by transferrin-receptor mediated endocytosis, requires further investigation. Brain Al citrate uptake has been attributed to the sodium-independent Lglutamate/ L-cystine exchanger system, system Xc-. Reports have suggested aluminum can compromise blood-brain barrier integrity, however the studies were conducted with aluminum concentrations greatly exceeding those seen in human blood plasma. Aluminum appeared …

Removing Aluminum From Solution Using Chelating Compounds And Immobilized Tethered Chelators, Robert A. Yokel, Wesley R. Harris, Christopher D. Spilling, Chang-Guo Zhan

Pharmaceutical Sciences Faculty Patents

Methods are described for removing aluminum from a solution using novel di- and tripodal compounds as chelators.

Aluminum Bioavailability From Tea Infusion, Robert A. Yokel, Rebecca L. Florence

Pharmaceutical Sciences Faculty Publications

The objective was to estimate oral Al bioavailability from tea infusion in the rat, using the tracer ²⁶Al. ²⁶Al citrate was injected into tea leaves. An infusion was prepared from the dried leaves and given intra-gastrically to rats which received concurrent intravenous ²⁷Al infusion. Oral Al bioavailability (F) was calculated from the area under the ²⁶Al, compared to ²⁷Al, serum concentration × time curves. Bioavailability from tea averaged 0.37%; not significantly different from water (F = 0.3%), or basic sodium aluminum phosphate (SALP) in cheese (F = 0.1 to 0.3%), but greater than acidic SALP …

Aluminum Bioavailability From Basic Sodium Aluminum Phosphate, An Approved Food Additive Emulsifying Agent, Incorporated In Cheese, Robert A. Yokel, Clair L. Hicks, Rebecca L. Florence

Pharmaceutical Sciences Faculty Publications

Oral aluminum (Al) bioavailability from drinking water has been previously estimated, but there is little information on Al bioavailability from foods. It was suggested that oral Al bioavailability from drinking water is much greater than from foods. The objective was to further test this hypothesis. Oral Al bioavailability was determined in the rat from basic [26Al]-sodium aluminum phosphate (basic SALP) in a process cheese. Consumption of approximately 1g cheese containing 1.5% or 3% basic SALP resulted in oral Al bioavailability (F) of approximately 0.1% and 0.3%, respectively, and time to maximum serum 26Al concentration (Tmax) of 8-9h. These Al bioavailability …

The Influence Of Citrate, Maltolate And Fluoride On The Gastrointestinal Absorption Of Aluminum At A Drinking Water-Relevant Concentration: A 26Al And 14C Study, Yuzhao Zhou, Wesley R. Harris, Robert A. Yokel

Pharmaceutical Sciences Faculty Publications

The objectives were to test the null hypotheses that (1) citrate, maltolate, and fluoride do not significantly influence oral Al bioavailability, C_max or T_max at an Al dose relevant to drinking water exposure; and (2) Al citrate and maltolate are absorbed intact from the gastrointestinal tract. Male Fisher rats were given 1 ml of solution intra-gastrically containing 1 nCi ²⁶Al (65 nmol total Al) as the Al³⁺ ion, or as complexes with ¹⁴C-citrate, ¹⁴C-maltolate or fluoride, during concurrent ²⁷Al iv infusion. Blood was repeatedly collected for serum ²⁶Al, total Al and ^{14 …}

Human Health Risk Assessment For Aluminium, Aluminium Oxide, And Aluminium Hydroxide, Daniel Krewski, Robert A. Yokel, Evert Nieboer, David Borchelt, Joshua Cohen, Jean Harry, Sam Kacew, Joan Lindsay, Amal M. Mahfouz, Virginie Rondeau

Pharmaceutical Sciences Faculty Publications

A compendium is provided of aluminium compounds used in industrial settings, and as pharmaceuticals, food additives, cosmetics and as other household products. Most aluminium compounds are solids exhibiting high melting points. The solubility of aluminium salts is governed by pH, because the aluminium(III)-cation (Al³⁺) has a strong affinity for the hydroxide ion, which promotes precipitation. Like Mg²⁺ and Ca²⁺ ions, Al³⁺ in most situations seeks out complexing agents with oxygen-atom donor sites such as carboxylate and phosphate groups, including in biological systems. Aluminium oxides, hydroxides and oxyhydroxides occur in numerous crystallographic forms, which exhibit different …

Aluminum Bioavailability From The Approved Food Additive Leavening Agent Acidic Sodium Aluminum Phosphate, Incorporated Into A Baked Good, Is Lower Than From Water, Robert A. Yokel, Rebecca L. Florence

Pharmaceutical Sciences Faculty Publications

There are estimates of oral aluminum (Al) bioavailability from drinking water, but little information on Al bioavailability from foods. Foods contribute ∼95% and drinking water 1–2% of the typical human's daily Al intake. The objectives were to estimate oral Al bioavailability from a representative food containing the food additive acidic sodium aluminum phosphate (acidic SALP), a leavening agent in baked goods. Rats were acclimated to a special diet that resulted in no stomach contents 14 h after its withdrawal. They were trained to rapidly consume a biscuit containing 1.5% acidic SALP. Oral Al bioavailability was then determined from a biscuit …

The Chemical Species Of Aluminum Influences Its Paracellular Flux Across And Uptake Into Caco-2 Cells, A Model Of Gastrointestinal Absorption, Yuzhao Zhou, Robert A. Yokel

Pharmaceutical Sciences Faculty Publications

Aluminum (Al) can cause neurotoxicity, a low-turnover osteomalacia, and microcytic anemia. To test the null hypothesis that the chemical form (species) of Al does not influence its mechanism or rate of absorption from the gastrointestinal tract, Al flux across and uptake into Caco-2 cells was investigated. Caco-2 cells were grown on porous membranes mounted in vertical diffusion chambers or in 35-mm-diameter plastic cell culture dishes. When 8 mM ²⁷Al was introduced as the ion, citrate, maltolate, fluoride, or hydroxide, the apical to basolateral apparent permeability (P_app) of Al correlated highly with the P_app of lucifer yellow …

26Al-Containing Acidic And Basic Sodium Aluminum Phosphate Preparation And Use In Studies Of Oral Aluminum Bioavailability From Foods Utilizing 26Al As An Aluminum Tracer, Robert A. Yokel, Aaron A. Urbas, Robert A. Lodder, John P. Selegue, Rebecca L. Florence

Pharmaceutical Sciences Faculty Publications

We synthesized ²⁶Al-containing acidic and basic (alkaline) sodium aluminum phosphates (SALPs) which are FDA-approved leavening and emulsifying agents, respectively, and used them to determine the oral bioavailability of aluminum incorporated in selected foods. We selected applicable methods from published syntheses (patents) and scaled them down (∼3000- and 850-fold) to prepare ∼300–400 mg of each SALP. The ²⁶Al was incorporated at the beginning of the syntheses to maximize ²⁶Al and ²⁷Al equilibration and incorporate the ²⁶Al in the naturally-occurring Al-containing chemical species of the products. Near infrared spectroscopy (NIR) and X-ray powder diffraction (XRD) were used …

Aluminium Content Of Some Foods And Food Products In The Usa, With Aluminium Food Additives, Salim M. Saiyed, Robert A. Yokel

Pharmaceutical Sciences Faculty Publications

The primary objective was to determine the aluminium (Al) content of selected foods and food products in the USA which contain Al as an approved food additive. Intake of Al from the labeled serving size of each food product was calculated. The samples were acid or base digested and analysed for Al using electrothermal atomic absorption spectrometry. Quality control (QC) samples, with matrices matching the samples, were generated and used to verify the Al determinations. Food product Al content ranged from < 1–27,000 mg kg⁻¹. Cheese in a serving of frozen pizzas had up to 14 mg of Al, from basic sodium …

Brain Uptake, Retention, And Efflux Of Aluminum And Manganese, Robert A. Yokel

Pharmaceutical Sciences Faculty Publications

My colleagues and I investigated the sites and mechanisms of aluminum (Al) and manganese (Mn) distribution through the blood-brain barrier (BBB). Microdialysis was used to sample non-protein-bound Al in the extracellular fluid (ECF) of blood (plasma) and brain. Brain ECF Al appearance after intravenous Al citrate injection was too rapid to attribute to diffusion or to transferrin-receptor-mediated endocytosis, suggesting another carrier-mediated process. The brain:blood ECF Al concentration ratio was 0.15 at constant blood and brain ECF Al concentrations, suggesting carrier-mediated brain Al efflux. Pharmacological manipulations suggested the efflux carrier might be a monocarboxylate transporter (MCT). However, the lack of Al …

Aluminium Toxicokinetics: An Updated Minireview, Robert A. Yokel, Patrick J. Mcnamara

Pharmaceutical Sciences Faculty Publications

This MiniReview updates and expands the MiniReview of aluminium toxicokinetics by Wilhelm et al. published by this journal in 1990. The use of ²⁶Al, analyzed by accelerator mass spectrometry, now enables determination of Al toxicokinetics under physiological conditions. There is concern about aluminium in drinking water. The common sources of aluminium for man are reviewed. Oral Al bioavailability from water appears to be about 0.3%. Food is the primary common source. Al bioavailability from food has not been adequately determined. Industrial and medicinal exposure, and perhaps antiperspirant use, can significantly increase absorbed aluminium. Inhalation bioavailability of airborne soluble Al …

The Toxicology Of Aluminum In The Brain: A Review, Robert A. Yokel

Pharmaceutical Sciences Faculty Publications

Aluminum is environmentally ubiquitous, providing human exposure. Usual human exposure is primarily dietary. The potential for significant Al absorption from the nasal cavity and direct distribution into the brain should be further investigated. Decreased renal function increases human risk of Al-induced accumulation and toxicity. Brain Al entry from blood may involve transferrin-receptor mediated endocytosis and a more rapid process transporting small molecular weight Al species. There appears to be Al efflux from the brain, probably as Al citrate. There is prolonged retention of a fraction of Al that enters the brain, suggesting the potential for accumulation with repeated exposure. Al …

Aluminum And Phosphorus Separation: Application To Preparation Of Target From Brain Tissue For 26Al Determination By Accelerator Mass Spectrometry, Russell D. Brauer, J. David Robertson, Pankaj Sharma, Robert A. Yokel

Pharmaceutical Sciences Faculty Publications

Acid digested brain containing 4 mg added ²⁷Al was ashed at 1000°C to prepare an Al₂O₃ target for accelerator mass spectrometry (AMS) analysis of ²⁶Al. A glass-like material usually resulted which was thought to be aluminum (Al) oxyphosphate. The separation of Al and phosphate was investigated. Al, but not phosphate, was bound by a cation exchange resin (AG 50-X8). Hydrofluoric acid eluted the Al from the resin. Removal of phosphate from acid digested brain by this method produced an amorphous material after ashing that was easier to recover from the porcelain crucible and had a …

The Biological Speciation And Toxicokinetics Of Aluminum, Emily Devoto, Robert A. Yokel

Pharmaceutical Sciences Faculty Publications

This review discusses recent literature on the chemical and physiological factors that influence the absorption, distribution, and excretion of aluminum in mammals, with particular regard to gastrointestinal absorption and speciation in plasma. Humans encounter aluminum, a ubiquitous yet highly insoluble element in most forms, in foods, drinking water, and pharmaceuticals. Exposure also occurs by inhalation of dust and aerosols, particularly in occupational settings. Absorption from the gut depends largely on pH and the presence of complexing ligands, particularly carboxylic acids, with which the metal can form absorbable neutral aluminum species. Uremic animals and humans experience higher than normal body burdens …

Effect Of Dietary Aluminum Sulfate On Calcium And Phosphorus Metabolism Of Broiler Chicks, Akmed S. Hussein, Austin H. Cantor, Thomas H. Johnson, Robert A. Yokel

Animal and Food Sciences Faculty Publications

The effect of dietary aluminum sulfate on Ca and P metabolism was studied using 1-day-oldmale broiler chicks. In Experiment 1, practical diets providing .90% Ca plus .45% available P (P_av), .90% Ca plus .78% P_av, 1.80% Ca plus .45% P_av, or 1.80% Ca plus .90% P_av were fed with 0 or .392% Al as aluminum sulfate for 21 days. The control diet (.90% Caplus .45% P_av) without added A1 was fed to all chicks during Days 22 to 49. In general, Al significantly (Pi), tibia breaking strength, tibia weight, percentage of …

Relationship Of Dietary Aluminum, Phosphorus, And Calcium To Phosphorus And Calcium Metabolism And Growth Performance Of Broiler Chicks, Akmed S. Hussein, Austin H. Cantor, Thomas H. Johnson, Robert A. Yokel

Animal and Food Sciences Faculty Publications

Dietary treatments providing three levels of added Al (0, .196, or .392%) as aluminum sulfate and of available phosphorus (P_av) (.45, .68, or .78%) in a factorial arrangement were administered to day-old chicks in Experiment 1. Plasma inorganic phosphorus (P_i) was significantly (P < .05) elevated by increasing P_av and was decreased by Al. Body weight gain, feed intake, and the gain:feed ratio at Day 21 were significantly decreased by increased concentrations of Al, but were unaffected by the P_av concentrations. Decreases of 39 and 73% in weight gain and of 34 and 66% in feed intake resulted from feeding …

Hair As An Indicator Of Excessive Aluminum Exposure, Robert A. Yokel

Pharmaceutical Sciences Faculty Publications

To determine if excessive systemic exposure to aluminum would be reflected in increased aluminum concentration in hair, rabbits were given a series of aluminum lactate injections. Hair was collected before the aluminum lactate administration from the site of injections and twice after the injections from this site as well as from an area adjoining the injection site. Aluminum was determined by flameless atomic absorption analysis of acid-digested samples. The concentration of aluminum in the hair increased after the injections in samples taken at both times from both sites. Considerable variability in hair aluminum was found before excessive exposure, as has …