rat

2.5% Al sulfate in drinking water (0.2% Al)

3-5 weeks

• altered cerebellar glutamate-nitric oxide-cGMP pathway:
• decreased N-methyl-D-aspartate-induced extracellular cGMP increase
• increased s-nitroso-N-acetyl penicillamine-induced extracellular cGMP increase
• reduced cerebellar calmodulin and nitric oxide synthase levels
• reduced basal activity of guanylate cyclase
• decreased basal extracellular cGMP levels

rat

gavage: 320 mg Al/kg-bw per day (as AlCl₃)

4 and 14 days
or 60 days

• increased acetylcholinesterase activity in olfactory bulb, striatum and hypothalamus (4 and 14 days)
• decreased acetylcholinesterase activity (60 days)

mouse

purified diet + 2000, 4000 or 6000 µg
Al/g diet (as Al acetate)

purified diet + 2000 or 4000 µg Al/g diet (as Al acetate)

2 weeks



8 weeks

• decreased glutathione levels in brain (2 weeks - high exposure, 8 weeks -
  high exposure)
• thiobarbituric acid reactive substances (TBARs) increased (lipid peroxidation)
  (8 weeks - both exposures)
• effects ameliorated by co-administration of vitamin E

rat

1600 mg Al/L in drinking water (as AlCl₃)

90 days

• impaired step-down test performance (passive avoidance)
• impaired Morris water maze performance
• no effect on acetylcholinesterase activity

rat

0.5 ppm AlF₃ in drinking water

52 weeks

• damaged and abnormal neurons and decreased neuronal density in
  hippocampus and neocortex

rat

standard diet + 250 mg
AlCl₃·6H₂O/kg-bw per day

6 weeks

• decreased thiol levels in brain
• decreased brain glutathione reductase and ATPase activities
• no significant effect on TBARs or glutathione-S-transferase

rat

5 or 20 mg AlCl₃/kg-bw per day in drinking water

6 months

• temporal cortex - reduced cell density in ganglionic layer and spongiform changes (high exposure)
• hippocampus - neurofilaments, deformity and vacuolization of nuclei (high exposure)

rat

50 or 100 mg Al/kg-bw per day (as Al(NO₃)₃·9H₂O in drinking water) + 355 and 710 mg citrate/kg-bw per day, respectively

6.5 months

• decreased calcium concentrations in brains of old rats (16 months) (high exposure)
• decreased manganese concentrations in brains of your (21 days) and adult (8 months) rats (high exposure)
• decreased copper and zinc concentrations in brains of young (21 days) rats
  (high and low exposure)
• decreased iron concentrations in brains of young (21 days) rats (high
  exposure)
• no effect on brain magnesium concentrations

monkey

gavage: 25 mg Al/kg-bw every second day (as Al lactate)

52 weeks

• decreased total lipid, glycolipid and phospholipid content of brain
• increased cholesterol levels and phospholipid to cholesterol ratio in brain
• increased lipid peroxidation (hippocampus > cerebral cortex > corpus striatum) and decreased ganglioside levels
• decreased Na⁺K⁺-ATPase, acetylcholinesterase and 2',3'-cyclic nucleotide
  phosphohydrolase activities in brain

rat

50 or 100 mg Al/kg-bw per day (as Al(NO₃)₃·9H₂O in drinking water) + 355 and 710 mg citrate/kg-bw per day, respectively

6.5 months

• no effects on open field activity
• no effects on shuttle box performance (passive avoidance)

rat

500 mg Al/L in drinking water (as AlCl₃)

12 months

• increased lipid peroxidation in brain (hippocampus and whole brain)
• decreased activities of superoxide dismutase, glutathione peroxidase and
  catalase

mouse

drinking water + 4.4 µg Al/L (as AlCl₃)

90 days

• decreased motor coordination (rota-rod)

rat

standard diet + 1 g Al/kg diet (as Al citrate)

6 months

• vacuolated astrocytes (cell body and processes)
• swollen astrocytic processes
• vacuolization of neuronal cytoplasm
• neuronal nuclear membrane indentations, vacuoles and inclusions

rat

0.5, 5 or 50 ppm AlF₃ in drinking water

45 weeks

• no effects on open field analysis and walking patterns (locomotor activity)
• no effects on balance beam test (motor coordination)
• no effects on T-maze performance (spontaneous alternation)
• no effects on water maze performance
• altered olfactory performance (medium and high exposure)

mouse

purified diet + 1000 µg Al/g diet (as AlCl₃) + 3.5% citrate

5-7 weeks

• decreased forelimb and hindlimb grip strength
• increased air puff startle response
• no effect on thermal sensitivity, negative geotaxis and auditory startle
• no change in brain TBARs or glutamine synthetase and alkaline phosphatase
  activities

rat

gavage: 30 or 100 mg AlCl₃/kg-bw per day, 300 mg Al(OH)₃/kg-bw per day or 100 mg Al(OH)₃/kg-bw per day + 30mg citrate/kg-bw per day

90 days

• impaired maze performance (all exposures)
• increased brain acetylcholinesterase activity (high exposure AlCl₃ and low
  exposure Al(OH)₃)
• decreased choline acetyltransferase activity (low exposure AlCl₃)

rat

500 mg Al/L in drinking water (as AlCl₃) (12 mg Al/day per rat)

180 days

• reduced spontaneous locomotor activity
• impaired acquisition, extinction and reacquisition of an active avoidance task
  shuttle box)
• impaired maze relearning ability
• increased brain lipid peroxidation
• reduced brain Mg²⁺- and Na⁺K⁺-ATPase acitivities

rat

0.5, 5 or 50 ppm AlF₃ in drinking water

45 weeks

• reduced numbers of neurons in hippocampus (all exposures)
• neurons in hippocampus disorganized (all exposures)

rat

adults: 0.3% Al₂(SO₄)₃·18H₂O in
drinking water

weanlings: 0.1-0.3% Al₂(SO₄)₃·18H₂O
in drinking water

3 months



8 weeks

• adults: decreased levels of microtubule associated protein-2 (MAP-2)
  (hippocampus and brain stem) and spectrin (hippocampus)
• weanlings: decreased MAP-2 levels in cortex and brainstem, increased cAMP
  levels and decreased inositol triphosphate levels in hippocampus

mouse

semi-purified diet + 1000 µg Al/g diet (as Al lactate)

90 days

• decreased motor activity, hindlimb grip strength and auditory and air puff
  startle responsiveness
• no effects on temperature sensitivity or foot splay
• no effect on lipid peroxidation (TBARs)

mouse

gavage: 17-172 mg Al/kg-bw per day (as Al₂(SO₄)₃·18H₂O or KAl(SO₄)2·12H₂O)

21 days

• multifocal, dose- and duration-dependent degeneration of nerve cells in
  cerebral cortex, subcortical region and base of brain (≥2.86 mg Al/kg-bw per
  day as Al₂(SO₄)₃·18H₂O or ≥4.86 mg Al/kg-bw per day as KAl(SO₄)2·12H₂O)

rat

gavage: 25 mg Al/kg-bw per day (asAl(NO₃)₃)

6 weeks

• brain dopamine and 5-hydroxytryptamine levels decreased, norepinephrine
  levels increased

mouse

purified diet + 500 or 1000 µg Al/g diet (as Al lactate)

10 weeks

• increased lipid peroxidation in brain (TBARs production) (high exposure)

rat

purified diet + 500 or 1000 µg Al/g diet (as Al lactate) (62 or 130 mg Al/kg-bw per day)

6 weeks

• decreased motor activity (high exposure)

rat

3.7% Al₂(SO₄)₃·18H₂O in drinking water (0.3% Al; 2.0 mmol Al/day per
rat)

30 days

• decreased retention of passive avoidance response
• no effect on open field activity

rat

3.7% Al₂(SO₄)₃·18H₂O in drinking water (0.3% Al; 2.0 mmol Al/day per
rat)

30 days

• impaired acquisition and retention of a passive avoidance learned response
• no effect on active avoidance response, radial arm maze or open field activity
• increased hippocampal muscarinic receptors
• no effect on choline acetyltransferase activity

rat

0.3% Al in drinking water (2.4% Al citrate [5.6 mmol Al/day per rat] or 3.7% Al₂(SO₄)₃·18H₂O [1.8 mmol Al/day per rat])

4 weeks

• increased cAMP levels in cerebellum, cortex, hippocampus and striatum
• increased cGMP levels in cerebellum and striatum (Al sulfate) and hippocampus (Al sulfate + citrate)
• choline levels decreased in cortex, hippocampus and striatum (Al citrate)

rat

100 µM AlCl₃ in drinking water

1 year

• impaired T-maze performance

rat - weanling

2400 mg Al(OH)₃/kg-bw per day in drinking water

60 days

• no effect on open field activity (horizontal or vertical movement)
• no effect on passive avoidance test
• no effect on radial maze performance
• some correlations between activity and brain aluminum levels

rat - adult

1513, 2697 or 3617 mg Al/kg-bw per day (as Al(OH)₃ in diet)

30 days

• no effect on open field activity (horizontal or vertical movement)
• no effect on passive avoidance test
• no effect on visual discrimination performance
• some correlations between test performance and brain aluminum levels

rat

standard diet + 0.2% Al (as AlCl₃)

12 weeks or 11months

• no effects on motor coordination (rota-rod) (12 weeks)
• reduced motor activity (both exposure durations)
• slowed acquisition of passive avoidance behaviour (shuttle box) (11 months)
• impaired retention of passive avoidance behaviour (12 weeks)

rat

gavage: 200, 400 or 600 mg AlCl₃·6H₂O/kg-bw per day or 195 mg Al(OH)₃/kg-bw per day

28 days

• increased general activity (open field maze)
• decreased motor coordination (rota-rod)
• increased sensitivity to flicker
• no effect on shuttle box performance (passive avoidance)

rat

gavage: 0.0025, 0.25 or 2.5 mg Al/kgbw per day

6-12 months

• slowdown in development and reinforcement of conditioned reflexes
• high value of index of latent stage of conditioned reflexes
• altered small movements