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

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 and chemical Al forms, different routes of administration, and different target organs in relation to the magnitude, frequency, and duration of exposure. Wide variations in diet can result in Al intakes that are often higher than the World Health Organization provisional tolerable weekly intake (PTWI), which is based on studies with Al citrate. Comparing daily dietary Al exposures on the basis of “total Al”assumes that gastrointestinal bioavailability for all dietary Al forms is equivalent to that for Al citrate, an approach that requires validation. Current occupational exposure limits (OELs) for identical Al substances vary as much as 15-fold. The toxicity of different Al forms depends in large measure on their physical behavior and relative solubility in water. The toxicity of soluble Al forms depends upon the delivered dose of Al+ 3 to target tissues. Trivalent Al reacts with water to produce bidentate superoxide coordination spheres [Al(O2)(H2O4)+ 2 and Al(H2O)6 + 3] that after complexation with O2•−, generate Al superoxides [Al(O2•)](H2O5)]+ 2. Semireduced AlO2• radicals deplete mitochondrial Fe and promote generation of H2O2, O2 • − and OH•. Thus, it is the Al+ 3-induced formation of oxygen radicals that accounts for the oxidative damage that leads to intrinsic apoptosis. In contrast, the toxicity of the insoluble Al oxides depends primarily on their behavior as particulates. Aluminum has been held responsible for human morbidity and mortality, but there is no consistent and convincing evidence to associate the Al found in food and drinking water at the doses and chemical forms presently consumed by people living in North America and Western Europe with increased risk for Alzheimer\u27s disease (AD). Neither is there clear evidence to show use of Al-containing underarm antiperspirants or cosmetics increases the risk of AD or breast cancer. Metallic Al, its oxides, and common Al salts have not been shown to be either genotoxic or carcinogenic. Aluminum exposures during neonatal and pediatric parenteral nutrition (PN) can impair bone mineralization and delay neurological development. Adverse effects to vaccines with Al adjuvants have occurred; however, recent controlled trials found that the immunologic response to certain vaccines with Al adjuvants was no greater, and in some cases less than, that after identical vaccination without Al adjuvants. The scientific literature on the adverse health effects of Al is extensive. Health risk assessments for Al must take into account individual co-factors (e.g., age, renal function, diet, gastric pH). Conclusions from the current review point to the need for refinement of the PTWI, reduction of Al contamination in PN solutions, justification for routine addition of Al to vaccines, and harmonization of OELs for Al substances

Aluminum toxicity in childhood

Aluminum intoxication is an iatrogenic disease caused by the use of aluminum compounds for phosphate binding and by the contamination of parenteral fluids. Although organ aluminum deposition was noted as early as 1880 and toxicity was documented in the 1960s, the inability to accurately measure serum and tissue aluminum prevented delineation of its toxic effects until the 1970s. Aluminum toxicity has now been conclusively shown to cause encephalopathy, metabolic bone disease, and microcytic anemia.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47831/1/467_2004_Article_BF00869743.pd

Serial cranial and spinal cord magnetic resonance imaging in multiple sclerosis.

Twenty-nine mildly disabled patients with multiple sclerosis underwent serial clinical and magnetic resonance imaging (MRI) evaluations (pre- and postgadolinium cranial and spinal cord MRI) on at least 3 occasions at 13-week intervals and during periods of suspected relapse. Using clinical judgment of the presence of recent active disease as the gold standard, combined MRI studies confirmed the clinical impression of active disease in 93% of follow-up visits (sensitivity) and the absence of active MS in 63% of follow-up visits (specificity). None of the cranial and spinal MRI-detected abnormalities disappeared. Gadolinium administration particularly increased the yield of spinal MRI. Cranial MRI alone detected 80% of the MRI-active visits. Clinical and MRI concordance was significantly better for the presence of recent disease activity than for the anatomical localization of the presumed site of activity. MRI evidence of apparent ongoing disease activity was seen more frequently in patients believed to have active multiple sclerosis in the preceding year (13 of 21) than in patients who had been in clinical remission for at least the 2 preceding years (2 of 8). Although clinical evidence of new disease activity was much less common in patients with active, chronic-progressive disease (1 of 8) than in patients with active, relapsing disease (9 of 13), the proportion of patients with either infrequent relapses, frequent relapses, or slow chronic-progressive disease in the preceding year in whom MRI activity developed and the pattern of this new MRI activity was similar between these types of active patients.(ABSTRACT TRUNCATED AT 250 WORDS

An open-trial evaluation of mitoxantrone in the treatment of progressive MS.

We treated 13 patients with progressive MS with mitoxantrone. All patients received a standard IV dose of mitoxantrone (8 mg/m2) every 3 weeks for a total of seven infusions, with dosage adjustments depending on the hematologic profile at the nadir. The treatment was well tolerated, with the most common side effect being mild nausea. Four of seven women developed transient secondary amenorrhea. The postenrollment clinical behavior of these patients was generally more favorable than during the 18 months prior to enrollment (only three of 13 patients developed an increase in the Expanded Disability Status Scale of more than 0.5 points), suggesting a possible treatment effect, but comparison with two historical control groups (both the active and placebo groups from the Canadian Cooperative Trial of Cyclophosphamide and Plasma Exchange) does not suggest that mitoxantrone was efficacious. Eight of 12 patients had evidence of MRI activity on 13 of 29 follow-up visits. This small, open-labeled pilot study did not provide strong support for proceeding with a randomized, controlled trial of this dosage regimen of mitoxantrone in patients with progressive MS