sarcomas were produced at the site of injection
of aluminum-dextran in mice. However, since
subcutaneous injection of aluminum-dextran is a
rather irrelevant model to assess aluminum carcino-
genicity, the significance of the positive results
appears questionable. (See Carcinogens: Carcino-
genic Substances in Food: Mechanisms.)
0021 Since aluminum and aluminum compounds are not
carcinogenic, or even show some antitumor activity
in laboratory animals, the negative results in most
short-term in vitro and in vivo mutagenic assays
(except some experiments in plants) are not surpris-
ing. (See Mutagens.)
0022 According to experimental data together with cer-
tain epidemiological evidence, it can be concluded
that aluminum and its salts do not constitute a
carcinogenic or mutagenic hazard except, perhaps,
in cases of extremely high exposure.
Miscellaneous
0023 No significant aluminum toxicity was observed when
aluminum nitrate nonahydrate was given orally to
rats at 375, 750 or 1500 mg per kg of body weight
per day for 1 month or over a period of 100 days at
360, 720, and 3600 mg per kg body weight per day.
However, it has been suggested that oral aluminum
exposure may both stimulate and suppress the
immune system, depending on the exposure level and
the physiological state of the animal and the immune
response assessed. Recent studies in rats have shown a
slight stimulation of some immune functions in the
rats at aluminum plasma concentrations normally
found in healthy humans (< 10 ng ml
1
).
Aluminum Toxicity in Humans
Dialysis Encephalopathy Syndrome
0024 Although the possible human toxicity of aluminum
has been a matter of controversy for over 100 years,
the spectrum of clinical aluminum toxicity has
expanded gradually since its initial description as
the cause of dialysis dementia. In the 1970s, Alfrey
et al. suggested that dialysis encephalopathy, pre-
viously a uniformly fatal neurological syndrome,
resulted from aluminum intoxication. Based on add-
itional biochemical and epidemiological data, this
supposition was confirmed, and now it is quite
accepted that aluminum is the cause of the dialysis
encephalopathy syndrome, the main neurotoxic con-
dition of aluminum. This syndrome includes a mild or
severe speech disorder, hallucinations, twitching,
myoclonus, seizures, mental changes and typical elec-
troencephalogram abnormalities. Moreover, there is
little doubt that aluminum can also cause bone
disease and anemia in dialysis patients. Individuals
with dialysis osteomalacia typically present with
severe symptoms of axial skeletal pain, proximal
muscular weakness, and fractures of the ribs, among
other symptoms. In turn, aluminum has also been
implicated as the cause of a microcytic, hypochromic
anemia in patients with chronic renal failure. These
disorders can result from introduction of aluminum
directly into the blood stream via high aluminum-
dialysate or consumption of large oral doses of
aluminum-containing phosphate binders. The lack
of urine production, which is the major route for
aluminum excretion, contributes to the problems in
these patients. While the health threat from diffusate
fluids was significantly reduced by the recommenda-
tion that the diffusate contains less than 10 mgof
aluminum per liter, ingesting aluminum-containing
phosphate binders is still a matter of concern for
uremic patients.
0025On the other hand, several reports have described
aluminum accumulation and toxicity in individuals
without chronic renal failure but with iatrogenic
exposure to aluminum. These include preterm
infants, largely fed intravenously, patients on total
parenteral nutrition, subjects with severe burns, indi-
viduals receiving alum irrigation in the urinary blad-
der to prevent bleeding, and patients undergoing
cranial bone reconstruction with aluminum contain-
ing bone cement.
Occupational Exposure
0026Occupational exposure to aluminum occurs not only
in the primary refining of this metal but also in user
industries (e.g., aircraft, automotive, metal products).
Aluminum welding is also an important exposure
vehicle. Although there are only a few studies on the
influence of occupational exposure to aluminum on
a worker’s cognitive performance, a diverse range of
cognitive deficits, including visuomotor or visuo-
spatial problems, attention deficits, impaired verbal
or visual memory and learning, and problems with
‘concept formation’ have been reported. Recent in-
vestigations have also corroborated that exposure
to aluminum is associated with detrimental effects
on certain cognitive functions, with deficits in
memory attention, and visuomotor and visuospatial
abilities.
0027For biological monitoring, urinary aluminum
appears to be a more sensitive index to current expos-
ure than serum levels. Workers with occupational
exposure to aluminum have shown statistically sig-
nificant increases in urinary aluminum/creatinine
ratios in association with borderline changes in
serum aluminum values. The mean aluminum con-
centrations in a healthy nonexposed population who
164 ALUMINUM (ALUMINIUM)/Toxicology