Urinary Excretion Of Aluminium Research Articles

Effect of an aluminum foil-processed diet on internal human aluminum burden

Background and purposeAluminum can be released into food by aluminum-containing food-contact materials (Al-FCM) during preparation or storage. There is considerable concern that extra aluminum intake may have negative effects on public health, especially with regard to its high background exposure and neurotoxic properties of aluminum in high exposures. Human in-vivo data on the additional aluminum load from Al-FCM, however, are lacking. As such, the objective of this study was to explore whether the consumption of a diet highly exposed to such products leads to an increased systemic Al load in real-world conditions. Materials and methodsAn exploratory, single-arm intervention study with a partially standardized diet was designed and carried out with 11participants. The same 10-day sequence of dishes was repeated three times. Participants were exposed to Al-FCM from Days 11 to 20, whereas control-phase meals were prepared without Al-FCM during the first and last 10–day periods. Spot urine samples were collected each morning and evening and analyzed for their aluminum concentration; appropriate contamination countermeasures were taken.Principal results: Urinary aluminum excretion showed a strong dependency on the creatinine concentration in urine and required adjustment in further analyses. The creatinine-adjusted aluminum excretion during the exposure phase (median 1.98 µg/g creatinine) was higher than in both control phases (1.78 µg/g creatinine each). Two different mixed-effects regression models showed a significant effect in the exposure phase. Considering a discrete time effect, the creatinine-adjusted mean increase in the exposure phase was estimated to be 0.19 µg/L (95% CI: 0.07–0.31; p = 0.0017).Major conclusions: This study demonstrated a measurable but fully reversible additional Al burden in humans from subacute Al-FCM exposure under real-world conditions. The estimated increase from Al-FCM corresponds to 8% of the baseline concentration. These data enable a more robust assessment of human health risks by Al-FCM.

Increased urinary excretion of aluminium after ingestion of the food additive sodium aluminium phosphate (SALP) – a study on healthy volunteers

ABSTRACTFood is an important source of human aluminium (Al) exposure and regular consumption of foods containing Al-based food additives may result in high Al intakes above health-based tolerable intakes. However, some additives are Al salts with low solubility, and little is known about bioavailability of Al in these additives. We investigated urine Al concentrations in healthy adult volunteers (N = 18, women/men) before (base-line) and after 7 days of ingestion of pancakes with a low Al content (median: <0.5 mg Al/kg) and high Al content (median: 860 mg/kg). The high-Al pancakes contained the common additive sodium aluminium phosphate (SALP). The participants did not know if the pancakes contained SALP or not during the experiment. After adjusting for creatinine content of the urine samples, median base-line Al concentrations before pancake ingestion were in the range 30–40 µmol Al/mol creatinine. Urine Al concentrations after ingestion of low-Al pancakes (average intake: <0.042 Al mg/day) did not differ significantly from the base-line levels. After ingestion of high-Al pancakes (72 mg Al/day) the median Al concentration in urine was more than 2-fold higher than at the base-line sampling before the high-Al pancake ingestion. At the end of the experiment the volunteers ingested an Al-containing antacid (Al-OH, 1800 mg Al/day) for 7 days as a positive control of Al absorption. This caused a 10-fold increase in median urine Al concentration compared to base-line. Our results strongly suggest that Al in the form of SALP in a pancake mix is bioavailable for absorption in humans, which should be taken into account in risk assessment of Al in food in countries with a high use of SALP as a food additive.

Urinary Excretion of Aluminium and Silicon in Secondary Progressive Multiple Sclerosis

BackgroundProgressive multiple sclerosis is a chronic autoimmune condition of unknown aetiology and few therapeutic options. Human exposure to aluminium has been linked with multiple sclerosis and affected individuals are known to excrete unusually high amounts of aluminium in their urine. Silicon-rich mineral waters facilitate the removal of aluminium from the body in urine and herein we have tested their efficacy in affecting urinary excretion of aluminium in individuals diagnosed with secondary progressive multiple sclerosis (SPMS). MethodsUrinary excretion of aluminium and silicon, measured using transversely-heated graphite furnace atomic absorption spectrometry, was determined in 15 individuals diagnosed with SPMS over 24weeks, a 12week baseline period (control) followed by a 12week treatment period, during which individuals consumed up to 1.5L of a silicon-rich mineral water every day. FindingsIndividuals with SPMS excreted high amounts of aluminium during the baseline period (135.2nmol/mmol Crt (70.3–222.2, n=180) and females excreted significantly more aluminium than males. Regular drinking of a silicon-rich mineral water increased the urinary excretion of aluminium significantly (349.0nmol/mmol Crt (231.7–524.7, n=180; three-way ANOVA, F1,13=59.17, p-value=0.000003) relative to the baseline period. The majority of individuals, 14 out of 15, excreted more aluminium (μmol/24h) following drinking of a silicon-rich mineral water (independent-test, p<0.05). Silicon-rich mineral waters may be an effective and non-invasive therapy for the removal of aluminium from the body of individuals with SPMS.

Influence of Essential Trace Minerals and Micronutrient Insufficiencies on Harmful Metal Overload in a Mongolian Patient with Multiple Sclerosis

Parkinson's disease and other neurological disorders are prevalent in Mongolia. Our previous studies revealed a significant correlation of these diseases with high oxidative stress due to a high body burden of harmful metals, such as manganese, iron, lead, cadmium, and aluminum. This report describes a 37-year-old male Mongolian patient with multiple sclerosis and essential micronutrient deficiency. This patient demonstrated high oxidative stress, as shown by high urinary 8-hydroxy-2'-deoxyguanosine levels of 14.7 and 14.3 ng/mg creatinine (crea), although his hair levels of these toxic metals were markedly lower than other Mongolians. In addition, this patient was deficient not only in various essential minerals, including selenium, magnesium, copper, cobalt, vanadium, and nickel, but also in micronutrients such as vitamin B6, C, E, folic acid, niacin, and β-carotene. Furthermore, after taking 2,3-dimercaptosuccinic acid, a chelating agent, urinary excretion of lead, cadmium, manganese, aluminum, iron, copper, and lithium were increased 156-, 8.4-, 7.6-, 4.3-, 3.3-, 2.1-, and 2.1-fold, respectively. These results suggest that this patient suffered from a deficiency in micronutrients such as essential minerals and vitamins, which resulted in a disturbance in the ability to excrete harmful metals into the urine and hair. It is possible that a deficiency of micronutrients and a high burden of heavy metals play a role in the pathogenesis of multiple sclerosis. Nutritional treatment may be an effective approach to this disease.

Chelation of aluminum by combining deferasirox and deferiprone in rats

The hypothesis that two known chelators deferasirox and deferiprone (L1) might be more efficient as combined treatment than as single therapies in removing aluminum from the body was tested in a new acute rat model. Seven-week-old male Wistar rats received chelators: deferasirox (orally [p.o.]), L1 (p.o.) or deferasirox + L1 as 100 or 200 mg/kg dose half an hour after a single intraperitoneal administration of 6 mg Al/kg body weight in the form of chloride. Serum aluminum concentration, urinary aluminum and iron excretions were determined by graphite furnace atomic absorption spectrometry. Both chelators were effective only at the higher dose level. While deferasirox was more effective than L1 in enhancing urinary aluminum excretion, L1 was more effective than deferasirox in enhancing urinary iron excretion. In the combined treatment group, deferasirox did not increase the L1 effect on aluminum and L1 did not increase the effect of deferasirox on iron elimination. Our results support the usefulness of this animal model for preliminary in vivo testing of aluminum chelators. Urinary values were more useful due to the high variability of serum results.

Aluminium in the human brain

An inevitable consequence of humans living in the Aluminium Age is the presence of aluminium in the brain. This non-essential, neurotoxic metal gains entry to the brain throughout all stages of human development, from the foetus through to old age. Human exposure to myriad forms of this ubiquitous and omnipresent metal makes its presence in the brain inevitable, while the structure and physiology of the brain makes it particularly susceptible to the accumulation of aluminium with age. In spite of aluminium’s complete lack of biological essentiality, it actually participates avidly in brain biochemistry and substitutes for essential metals in critical biochemical processes. The degree to which such substitutions are disruptive and are manifested as biological effects will depend upon the biological availability of aluminium in any particular physical or chemical compartment, and will under all circumstances be exerting an energy load on the brain. In short, the brain must expend energy in its ‘unconscious’ response to an exposure to biologically available aluminium. There are many examples where ‘biological effect’ has resulted in aluminium-induced neurotoxicity and most potently in conditions that have resulted in an aluminium-associated encephalopathy. However, since aluminium is non-essential and not required by the brain, its biological availability will only rarely achieve such levels of acuity, and it is more pertinent to consider and investigate the brain’s response to much lower though sustained levels of biologically reactive aluminium. This is the level of exposure that defines the putative role of aluminium in chronic neurodegenerative disease and, though thoroughly investigated in numerous animal models, the chronic toxicity of aluminium has yet to be addressed experimentally in humans. A feasible test of the ‘aluminium hypothesis’, whereby aluminium in the human brain is implicated in chronic neurodegenerative disease, would be to reduce the brain’s aluminium load to the lowest possible level by non-invasive means. The simplest way that this aim can be fulfilled in a significant and relevant population is by facilitating the urinary excretion of aluminium through the regular drinking of a silicic acid-rich mineral water over an extended time period. This will lower the body and brain burden of aluminium, and by doing so will test whether brain aluminium contributes significantly to chronic neurodegenerative diseases such as Alzheimer’s and Parkinson’s.

Elevated urinary aluminium in current and past users of illicit heroin

The use of illicit heroin is associated with aberrant neurology of unknown aetiology and various psychiatric illnesses. Aluminium, which is a proven neurotoxin, is present in significant amounts in illicit heroin and may also be volatilized and inhaled following the vaporization of heroin off aluminium foil ('Chasing the Dragon'). The purpose of this study was to establish if the use of illicit heroin was associated with an increase in the body burden of aluminium. We have used graphite furnace atomic absorption spectrometry to measure the aluminium and iron contents of the urine of current and past users of illicit heroin and used these data to estimate body burdens of aluminium. Urinary excretion of aluminium is the most effective non-invasive indicator of the body burden of aluminium and was found to be significantly (P < 0.001) higher in users of illicit heroin, range 14-3382 nmol/mmol creatinine (mean +/- SD; 222 +/- 491 nmol/mmol creatinine), than in a normal non-drug abusing control population, range 23-74 nmol/mmol creatinine (mean +/- SD; 43 +/- 19 nmol/mmol creatinine). Exposure to aluminium from the use of illicit heroin may be of particular significance because the urinary excretion of iron, another major contaminant of illicit heroin, in users (mean +/- SD; 53 +/- 63 nmol/mmol creatinine) was not significantly different (P > 0.05) from the control population (mean +/- SD; 38 +/- 18 nmol/mmol creatinine). We have shown for the first time that the use of illicit heroin may be a significant contributor to the body burden of aluminium. Further research will be required to determine if adventitious aluminium has a role in heroin use-related neuropathology and neurology.

Short report: plasma aluminium concentration and 24-hour urinary aluminium excretion before, during and after treatment with sucralfate

Ten dyspeptic patients were treated with 1 g sucralfate q.d.s. for six weeks. The plasma aluminium concentration and 24-h urinary aluminium excretion were measured at 3-weekly intervals before, during and after treatment with sucralfate. Compared with before treatment, there were significant rises in the median plasma aluminium concentration at 3 and 6 weeks during treatment with sucralfate (6 micrograms/L to 13 and 12 micrograms/L). The median 24-h urinary aluminium excretion rose significantly from a pretreatment level of 20 micrograms to 71 and 78 micrograms after 3 and 6 weeks of treatment; the significant increase of urinary aluminium excretion persisted for three weeks after cessation of treatment (52 micrograms/24 hours), but thereafter urinary excretion was not significantly different from pretreatment. The results are consistent with significant absorption and tissue accumulation of aluminium during standard treatment with sucralfate in individuals with normal renal function.

A vexing Commentary on the important issue of aluminium and Alzheimer' disease

The Commentary by Zatta [9] on our recent publication [4] is error strewn and interwoven with unsubstantiated claims which can only serve to blur the edges not only of the research published in our paper but also the general question of the role of aluminium in Alzheimer’s disease [2]. It is perhaps surprising that someone who has built his scientific reputation on the investigation of the putative role of aluminium in AD should now present such a prejudiced view. The essence of Zatta’s piece is immediately clear from its title. The use of the term ‘Vexata Questio’ implies that putting aluminium and AD together is to act in a malicious, irritating and even trivial manner. He is imploring the reader as to why he/she should have to waste his/her time considering aluminium and AD and not least because of new data [4] which he believes leaves more to the imagination than to the scientific method. His major unsubstantiated criticism is ‘modestly’ reiterated at the end of the Commentary and concerns the scientific method and statistical analyses. The research in our paper has been peer-reviewed and it is unfortunate that Zatta’s Commentary includes unsubstantiated opinions on its validity, opinions which can only serve to seed doubt in the scientific rigour of our findings. Another criticism with which he sought to reject our research was that the mineral water in question would include other constituents which could be responsible for the observed reduction in the body burden of aluminium. When challenged to explain this allusion he now reports in his Commentary that the 8.0 mg/L magnesium in Volvic could be responsible for the observed changes in the excretion of aluminium through an unsupported mechanism which he calls ‘the domino effect’. We have trawled through the literature on both animal and human studies to try to find one example of how drinking water containing 8.0 mg/L magnesium influenced the urinary excretion of aluminium. There are no data to support any such effects and presumably Zatta’s lack of any reference to such shows that he is aware of this. This does not, of course, prevent him from making this statement and using it along with his unsubstantiated criticisms of our scientific method as basis to reject our research. Zatta now turns his attentions to the general subject areas of aluminium, silicon and AD. I found his manner to be condescending and his reference to JD Birchall FRS ill-informed and unnecessary. He also gives the impression that he is unaware that what he calls ‘the old story’ has moved on and, as exemplified by our JAD paper, continues to this day, relying only upon sound science for its substance (see, http:// www.keele.ac.uk/depts/ch/groups/aluminium/publications.htm). However, Zatta’s understanding of the bioinorganic chemistry of silicon is very much an ‘old story’. It has been acknowledged for at least the last twenty years that there are no Si-C, Si-N, Si-O-C . . . etc. bonds in any form of life on Earth [8], though we are still looking for these up to this day, and therefore Zatta’s allusion to silicon being ‘usually bonded to glycoproteins’ is to say the least, ill-informed. The reference to the silicon concentration of blood is similarly out-dated, the lowest

Non-invasive therapy to reduce the body burden of aluminium in Alzheimer's disease

There are unexplained links between human exposure to aluminium and the incidence, progression and aetiology of Alzheimer's disease. The null hypothesis which underlies any link is that there would be no Alzheimer's disease in the effective absence of a body burden of aluminium. To test this the latter would have to be reduced to and retained at a level that was commensurate with an Alzheimer's disease-free population. In the absence of recent human interference in the biogeochemical cycle of aluminium the reaction of silicic acid with aluminium has acted as a geochemical control of the biological availability of aluminium. This same mechanism might now be applied to both the removal of aluminium from the body and the reduced entry of aluminium into the body while ensuring that essential metals, such as iron, are unaffected. Based upon the premise that urinary aluminium is the best non-invasive estimate of body burden of aluminium patients with Alzheimer's disease were asked to drink 1.5 L of a silicic acid-rich mineral water each day for five days and, by comparison of their urinary excretion of aluminium pre-and post this simple procedure, the influence upon their body burden of aluminium was determined. Drinking the mineral water increased significantly (P<0.001) their urinary excretion of silicic acid (34.3 +/- 15.2 to 55.7 +/- 14.2 micromol/mmol creatinine) and concomitantly reduced significantly P=0.037) their urinary excretion of aluminium (86.0 +/- 24.3 to 62.2 +/- 23.2 nmol/mmol creatinine). The latter was achieved without any significant (P>0.05) influence upon the urinary excretion of iron (20.7 +/- 9.5 to 21.7 +/- 13.8 nmol/mmol creatinine). The reduction in urinary aluminium supported the future longer-term use of silicic acid as non-invasive therapy for reducing the body burden of aluminium in Alzheimer's disease.

The silicon link between aluminium and Alzheimer's disease

Christopher Exley and colleagues report in this issue of JAD [15] the results of a clinical study showing that drinking silicic acid (Si(OH)4)-rich mineral water for five days significantly reduces the urinary excretion of aluminium, but not iron in Alzheimer disease (AD) patients. The authors argue that the long-term dietary supplementation of Si(OH)4 might qualify as a non-invasive therapy for reducing the body burden of aluminium in AD. This study opens a new chapter of the investigations of J. Derek Birchall’s hypothesis of a silicon link between aluminium and AD, for it offers a direct demonstration of the efficacy of dietary silica supplementation in increasing the excretion of aluminium in AD. But what can we expect in terms of therapeutic effects from stimulating the aluminium urinary excretion in AD? We will briefly discuss here the context and implications of this study. The systematic interest for the utilization of silicon in medicine can be traced back to the late nineteenth century, when the emulation of physiologists for research on this element led Luis Pasteur to predict that silicon reserved important therapeutic applications in many human diseases. However, the recognition of silicon as an essential trace element came only in 1972 when two reports showed that dietary silicon deprivation in chicks and rats was associated with retarded growth and bone deformities [6,28]. Subsequent research has established that silicon is indeed important for the calcification of bone and cartilage, and it may be thus involved in disorders characterized by an imbalance between bone formation and resorption (e.g., osteoporosis), joint disorders (e.g., osteoarthritis), and even heart disease and aging (for review see [27]). In contrast to the rather straightforward demonstrations of the roles of silicon in bone and connective tissue homeostasis, the link between silicon and neuropathology and particularly AD was put forward via the aluminium hypothesis in AD. Taking account of the high chemical affinity of silicon for aluminium, and the typical inverse relation between the concentrations of aluminium and silicon in water supplies, the British chemist J.D. Birchall suggested that silicon might mediate the effect of aluminium from drinking water on AD incidence [2,3]. This suggestion was partly based on an earlier finding reported by Birchall, Exley and coworkers that Si(OH)4 in water protected salmon against fatal ionoregulatory, osmoregulatory and respiratory dysfunctions caused by toxic aluminium binding to the gill epithelium [4,14]. Following Birchall’s suggestion, several epidemiological studies reviewed in [19] (see also [20]) indicated that the protective effect of silicon from drinking water against AD was only modest. Nonetheless, in spite of this apparent rebuttal of Birchall’s hypothesis, the silicon link between aluminium and AD continued to be supported on other lines of research. For instance, silicon, more specifically as silica oligomers [21], reduced by several folds the gastrointestinal absorption of aluminium in humans [11] and increased its urinary excretion [1], as originally suggested [2]; high serum silicon was shown

Elevated urinary excretion of aluminium and iron in multiple sclerosis

Multiple sclerosis (MS) is a chronic, immune-mediated, demyelinating disease of the central nervous system of as yet unknown aetiology. A consensus of opinion has suggested that the disorder is the result of an interplay between environmental factors and susceptibility genes. We have used a battery of analytical techniques to determine if the urinary excretion of i) markers of oxidative damage; ii) iron and iii) the environmental toxin aluminium and its antagonist, silicon, are altered in relapsing remitting (RRMS) and secondary progressive MS (SPMS). Urinary concentrations of oxidative biomarkers, MDA and TBARS, were not found to be useful indicators of inflammatory disease in MS. However, urinary concentrations of another potential marker for inflammation and oxidative stress, iron, were significantly increased in SPMS (P<0.01) and insignificantly increased in RRMS (P>0.05). Urinary concentrations of aluminium were also significantly increased in RRMS (P<0.001) and SPMS (P<0.05) such that the levels of aluminium excretion in the former were similar to those observed in individuals undergoing metal chelation therapy. The excretion of silicon was lower in MS and significantly so in SPMS (P<0.05). Increased excretion of iron in urine supported a role for iron dysmetabolism in MS. Levels of urinary aluminium excretion similar to those seen in aluminium intoxication suggested that aluminium may be a hitherto unrecognized environmental factor associated with the aetiology of MS. If aluminium is involved in MS then an increased dietary intake of its natural antagonist, silicon, might be a therapeutic option.

Elevated urinary excretion of aluminium and iron in mulitple sclerosis

Elevated urinary excretion of aluminium and iron in mulitple sclerosis

Aluminum Contamination of Parenteral Nutrition and Aluminum Loading in Children on Long‐Term Parenteral Nutrition

ABSTRACTBackgroundChildren who are receiving parenteral nutrition are at risk of aluminum overload, which may contribute to such side effects as osteopenic bone disease. The aim of the present study is to determine the aluminum contamination of parenteral nutrition solutions and their components, and to assess the aluminum status of children on long‐term parenteral nutrition.MethodsAluminum concentrations were determined by graphite furnace absorption spectroscopy in components and in final parenteral nutrition solutions. The urinary aluminum excretion and plasma aluminum concentration were determined in 10 children on long‐term parenteral nutrition.ResultsThe mean aluminum concentration in the administered parenteral nutrition solutions was 1.6 ± 0.9 μmol × l−1(mean ± standard deviation (SD)). The resulting mean aluminum daily intake of the 10 patients was 0.08 ± 0.03 μmol × kg−1 × day−1.ConclusionsCompared to two previous studies performed in 1990 and in 1995 in our hospital, the aluminum contamination of parenteral nutrition solutions and the daily aluminum intake of the children seemed to decrease. However, the plasma aluminum concentration and daily urinary aluminum excretion of the children still remain above normal standards. The children had no clinical symptoms of bone disease but aluminum accumulation in tissue can not be excluded. To prevent this iatrogenic toxicity, the aluminum contamination of parenteral nutrition should be assessed regularly.

Aluminum contamination of parenteral nutrition and aluminum loading in children on long-term parenteral nutrition.

Children who are receiving parenteral nutrition are at risk of aluminum overload, which may contribute to such side effects as osteopenic bone disease. The aim of the present study is to determine the aluminum contamination of parenteral nutrition solutions and their components, and to assess the aluminum status of children on long-term parenteral nutrition. Aluminum concentrations were determined by graphite furnace absorption spectroscopy in components and in final parenteral nutrition solutions. The urinary aluminum excretion and plasma aluminum concentration were determined in 10 children on long-term parenteral nutrition. The mean aluminum concentration in the administered parenteral nutrition solutions was 1.6 +/- 0.9 micromol x l(-1)(mean +/- standard deviation (SD)). The resulting mean aluminum daily intake of the 10 patients was 0.08 +/- 0.03 micromol x kg(-1) x day(-1). Compared to two previous studies performed in 1990 and in 1995 in our hospital, the aluminum contamination of parenteral nutrition solutions and the daily aluminum intake of the children seemed to decrease. However, the plasma aluminum concentration and daily urinary aluminum excretion of the children still remain above normal standards. The children had no clinical symptoms of bone disease but aluminum accumulation in tissue can not be excluded. To prevent this iatrogenic toxicity, the aluminum contamination of parenteral nutrition should be assessed regularly.

The influence of fluoride ingestion on urinary aluminum excretion in humans.

Fluoride (F) and aluminum (Al) are both ingested daily in water, foods, and pharmaceuticals. Owing to the strong chemical affinity between F and Al, these elements can interact in biological systems. The purpose of the present study was to investigate the influence of F ingestion on Al excretion in humans. Six healthy volunteers ingested 100 ml of distilled water at 6:00 a.m. on day 1 (control period) and the same volume of sodium fluoride solution containing 5 mg of F at 6:00 a.m. on day 2 (test period). A schedule for meals and for blood and urine collection was followed for the two successive days. The concentration of F was measured with an F-electrode, and Al was determined by ion-pair RP-HPLC with its complexation with 8-quinolinol. The mean concentration of serum F peaked within 30 minutes after ingestion of F and rapidly decreased thereafter, reaching baseline 24 hours later. In control period, there was no increase of Al concentration in serum in 24 hours. In test period, Al concentration in serum did not increase significantly compared with those in control serum. Although some variation was observed among subjects, cumulative amounts of F and Al excreted in urine during the test period were significantly higher than those during the control period. The results suggest that absorbed F enhanced urinary Al excretion and that the Al in urine may be, at least in part, derived from endogenous tissues.

Aluminium uptake and excretion in potroom workers of a new primary aluminium smelter during the construction stage.

The aim of this study was to define bio-accumulation and excretion patterns of aluminium in newly employed potroom workers as well as changes in ambient aluminium levels in the potrooms of a modern aluminium smelter during the plant construction stage and one year into full production. A study was carried out on 115 newly employed volunteer potroom workers at various intervals, over a total period of 36 months. Before commencement of employment a structured questionnaire was completed by all study participants and the first collection of blood and urine specimens took place. As none of the subjects had ever worked in the aluminium industry before, they also served as their own controls. Atomic absorption spectroscopy was used to measure the aluminium content in the biological fluids and the content of the metal in the ambient air of the potrooms. Significantly, the study found an early and marked biological response to inhalation of very low levels of airborne aluminium. After only 12 months, the mean concentration of aluminium in serum had almost doubled; thereafter it levelled off. A mixed model analysis did not find any differences in the concentrations of aluminium in the serum of the subjects since the variation between subjects at any given time was much smaller than the variation within subjects. This may be an indication of the pronounced effect of aluminium inhalation on the kinetics of this metal in the human body. Furthermore, urinary excretion of aluminium by the potroom workers showed a linear increase reaching a concentration of only 49 microg l(-1) at the 36 month stage, suggesting a slow rate of elimination.

Ingestion and excretion of aluminum in foods and pharmaceuticals

We measured the aluminum contents in foods and pharmaceuticals, and the aluminum concentrations in urine by atomic absorption spectrophotometry with polarized Zeeman background correction to obtain the daily intake and excretion of aluminum. The daily urinary excretions of aluminum in healthy females were obtained after consuming sea algae, hizikia fusiforme, which has a high aluminum contents. Daily aluminum excretion did not increase after taking hizikia fusiforme. On the other hand, high aluminum excretions were observed after taking an analgesic/antipyretic with a high aluminum contents, compared with the usual daily aluminum excretion (p < 0.001), and compared with after taking an analgesic/antipyretic with no aluminum (p < 0.0001). We found that the daily urinary excretion of aluminum was not related to the total consumption of aluminum, but depended on the binding state of aluminum consumed.

Bone aluminum uptake in uremic rats receiving intraperitoneal iron.

To assess the effect of concomitant iron and aluminum loads on bone aluminum accumulation and on the response to the deferoxamine test in rats with the same aluminum surcharge, Wistar rats with chronic renal failure were divided into three groups: iron-overloaded rats (N = 6) (intraperitoneal iron); iron-depleted rats (N = 6) (blood withdrawal two to three times per week); control rats (N = 4) (no manipulation). All groups received intraperitoneal aluminum simultaneously. After 6 wk, a deferoxamine challenge test was performed. Thereafter, bone aluminum and iron were measured. The iron-overloaded rats showed higher bone iron content (iron overloaded: 147.7+/-55.4 microg/g; iron depleted: 7.9+/-1.0, and controls 13.3+/-9.9 microg/g, p < 0.010) and lower bone aluminum content (iron overloaded: 14.2+/-4.0 microg/g; iron depleted: 70.9+/-35.1 microg/g; controls: 72.7+/-28.3 microg/g p < 0.005). No differences were found between the iron-depleted and control rats. After the deferoxamine infusion, the iron-depleted rats tended to have higher serum aluminum increments (p = NS) and higher urinary aluminum excretion (p < 0.012, p < 0.020) than control rats despite similar amounts of aluminum in bone of the two groups. Aluminum bone accumulation was minor if iron and aluminum loads were given concomitantly. The iron depletion influenced the results of the deferoxamine challenge test in rats with similar bone aluminum burden.

Chelation of aluminium by combining DFO and L1 in rats

The hypothesis that two known chelators 1,2-dimethyl-3-hydroxypyrid-4-one (L1) and desferrioxamine (DFO) might be more efficient as combined treatment than as monotherapies in removing aluminium from the body was tested in a new acute rat model. Five-week old female rats received chelators: L1 (p.o.), DFO (i.p.) or L1+DFO as 100 or 200 mg/kg dose half an hour after a single i.p. administration of 6 mg Al/kg body weight in the form of chloride. Serum aluminium concentration and urinary aluminium and iron excretions were determined by electrothermal or flame atomic absorption spectrometry. Both chelators were effective only at the higher dose level. While DFO was more effective than L1 in enhancing urinary aluminium excretion, L1 was more effective than DFO in enhancing urinary iron excretion. In the combined treatment group L1 did not increase the DFO effect on aluminium and DFO did not increase the effect of L1 on iron elimination. However, in this group a simultaneous increase in both aluminium and iron elimination was observed. Our results support the usefulness of this animal model for preliminary in vivo testing of aluminium chelators. Urinary values were more useful because of the high variability of serum results. Result of combined chelators treatment should be confirmed in a different experimental model before extrapolation to other systems. This testing procedure of course does not provide all the relevant answers for evaluating the efficiency of chelating agents in aluminium toxicity.