| | Aluminum source/compound | Dose & duration | Route | Species | Adverse effects |
| | Standard infant feeding solution | ~20 μg/kg/day,
>10 days | Intravenous (parenteral) | Human, premature infants | Reduced developmental attainment at the corrected post-term age of 18 months, as evidenced by significantly lower Bayley Mental Development Index (BMDI) scores (mean loss of one point on the BMDI/day of full intravenous feeding, after adjustment for potentially confounding factors) compared to infants fed with Al-depleted solutions [31]. |
| | Al-containing dialysis fluid (derived from Al-sulfate treated tap water) | 1 ppm, chronic
(2–5 years) | Intravenous | Human, dialysis patients (15–61 years old at the start of the dialysis treatment) | Speech impairments (stuttering, dysarthria, dyspraxia, and motor aphasia), movement disorders (twitches, tremors, myoclonic jerks, seizures, and motor apraxia), cognitive impairments and behavioural changes (progressive dementia, paranoia, confusion, and psychosis), and death [32]. |
| | Al-containing antacids | Chronic | Oral | Human infants | Craniosynostosis (premature ossification of the skull and obliteration of the sutures) [33]. |
| | Various dietary | Chronic | Oral | Elderly human subjects | Impaired visuomotor coordination, poor long-term memory, and increased sensitivity to flicker (correlated with high Al-serum levels) [34]. |
| Al sulfate
(present as flocculant in potable water supplies, accidentally released in high amounts) | 500–3000 x the acceptable limit under European Union Legislation (0.200 mg/L), chronic (15 years) | Oral | Human adult (female, 44 years old) | Sporadic early-onset β amyloid angiopathy (Alzheimer’s-related disease), difficulty in finding words, progressive dementia, visual hallucinations, headache, anxiety, cerebral ischemia, and death [35]. |
| | Al-containing food pellets | 0.5–1.7 mg/kg/day (typical human), chronic (22–32 months) | Oral | Rats, 6 months old at the start of treatment | Cognitive deterioration and impaired performance in learning tasks, impaired concentration, and behavioral changes including confusion and repetitive behaviour [36]. |
| | Al lactate | 500–1000 ppm, chronic (during gestation and lactation) | Oral | Mice dams | Hind limb paralysis, seizures, and death (dams), lower neurobehavioral development and altered performance on a neurobehavioral test battery in pups (foot splay, forelimb, and hind limb grip strengths reduced) [37]. |
| | Al hydroxide as a vaccine adjuvant | 1–17 doses of Al-containing vaccines (hepatitis B, hepatitis A, and tetanus toxoid) in the period of 10 years prior to disease diagnosis | Intramuscular injection | Human adult macrophagic myofasciitis (MMF) syndrome patients (mean age 45 years) | MMF typical clinical manifestations: myalgia, arthralgia, chronic fatigue (disabling fatigue >6 months), muscle weakness and cognitive dysfunction (overt cognitive alterations affecting memory, and attention manifested in 51% of cases) [38–41].
Typical histopathology: presence of granulomatous myopathological lesion comprised of Al-hydroxide-loaded macrophages at the site of vaccine injection (usually deltoid muscle); persistence of Al long-term, up to 8–10 years in postinjection mice [38, 39, 42].
15–20% MMF patients concurrently develop an autoimmune disease, most frequently being multiple sclerosis-like demyelinating disorders, Hashimoto’s thyroiditis, and diffuse dysimmune neuromuscular diseases (i.e., dermatomyositis, necrotizing autoimmune myopathy, myasthenia gravis, and inclusion body myositis); even in the absence of overt autoimmune disease, low titres of autoantibodies, increased inflammatory biomarkers, and abnormal iron status commonly detected in exposed mice [38, 39]. |
| | Al hydroxide as a vaccine adjuvant | 14 injections over a 6-month period | Subcutaneous | Sheep, male 3 month old lambs | “Sheep adjuvant syndrome” first identified following mass-vaccination for bluetongue; experimentally reproduced by repetitive injection with Al-containing vaccines [14]; observed in acute form (affecting 25% of exposed flocks, 0.5% animals within a flock) and chronic phase form (affecting 50–70% of all exposed flocks and up to 100% of animals within a given flock).
Acute phase symptoms: lethargy, reluctance to move, bruxism (teeth grinding), transient blindness, nystagmus (rapid abnormal eye movements), stupor, abnormal behavior, disorientation, and a low response to external stimuli, seizures, and occasionally death; histopathological lesions mainly consisting of acute meningoencephalitis (similar to those observed in humans postvaccination) and demyelinating foci
Chronic phase symptoms: severe neurobehavioral outcomes including restlessness, compulsive wool biting, generalized weakness, muscle tremors, loss of response to stimuli, ataxia, tetraplegia (paralysis of all four limbs), stupor, coma, and death. Inflammatory lesions (multifocal neuronal necrosis and neuron loss in both dorsal and ventral column of the gray matter) and presence of Al in CNS tissues [43]. |
| | Al hydroxide as a vaccine adjuvant | 2 injections,
2 weeks apart | Subcutaneous injection (behind the neck) | Mice, 3 months old CD-1 male | Motor neuron degeneration and apoptosis, motor function deficits, decrease in strength, cognitive deficits, and decreased performance in learning tasks, decrements in spatial memory, activation of microglia [44, 45]. |
| | Al oxide fumes, occupational exposure | 0.13–1.95 mg/m3, chronic | Inhalation | Human, adults
(mean age 39 years) | Headache, emotional irritability, concentration difficulty, insomnia, mood lability [46]. |
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