Aluminium sulphate

Neurotoxicity

Description of key information

Orale exposure:
The results of the study  of Al Moutaery 2000, clearly indicate that the neurological function and recovery rate following SCI are significantly impaired in rats exposed to aluminum sulphate at 250 mg/kg/bw day (LOAEL).
Inhalation exposure:
No brain weight or histological changes were observed in Fischer 344 rats or Hartley guinea pigs exposed by inhalation to up to 38.6 mg /m3  for 6 months (Steinhagen et al. 1978). 
Dermal exposure:
No studies were located regarding neurological effects in humans after acute- or intermediate-duration dermal exposure to various forms of
 aluminum. 
 
For dermal exposure we taken that:
-the average weight of rats is 250g (200-300g),
-the dose is applied over an area which is approximately 10% of the total body surface=0.025 kg
corrected dermal LOAEL= oral LOAEL
250 mg/kg bw/day 0.025 kg =
LOAELrat 6.3 mg/kg bw/day

Key value for chemical safety assessment

Effect on neurotoxicity: via oral route

Endpoint conclusion

Dose descriptor:

LOAEL

250 mg/kg bw/day

Effect on neurotoxicity: via inhalation route

Endpoint conclusion

Dose descriptor:

NOAEC

38.6 mg/m³

Effect on neurotoxicity: via dermal route

Endpoint conclusion

Dose descriptor:

LOAEL

6.3 mg/kg bw/day

Additional information

Orale exposure:

LABORATORY ANIMALS: Neurotoxicity/.Pregnant mice were injectedintraperitoneally with 200 mg/kg aluminum-sulfate or saline from days 10 to13 of gestation inclusive. A second group of pregnant mice was givenaluminum-sulfate at 750 milligrams/liter as their sole drinking water fromdays ten to 17 of gestation inclusive. Offspring were sacrificed at agesranging from 3 to 44 weeks for determination of choline-acetyltransferaseactivity. For behavioral and developmental studies, pups were crossfostered on postnatal day one. Pups were tested for slow righting, cliffaversion, forelimb grasping, pole grasping, climbing on a wire mesh, andeye opening. At 10 weeks, male mice were tested in an eight arm radialmaze. At 22 weeks, adult activity tested were carried out. The cholinergicsystem, as evaluated by the activity of choline-acetyltransferase, wasaffected differentially in different regions of the brain and still showedsignificant effects in the adult. Differences between the intraperitonealand oral series in the magnitude of effect seen in the regions of thebrain probably reflect differences in the effective level of exposure.

Growth rate and psychomotor maturation in the preweaning mouse wereaffected in the intraperitoneal series only, showing a marked postnatal maternal effect. [Clayton RM et al; Life Sci 51 (25): 1921-1928 (1992

/LABORATORY ANIMALS: Neurotoxicity/:Male, 1 day old white-leghorn-chicks were fed 200 or 400mg/kg aluminum-sulfate (10043013) for 15 days. Cerebral hemispheres were analyzed 24 hours after the last feeding. Cerebral hemisphere tissue homogenates prepared from 1 and 56 day old chicks were incubated with various concentrations of aluminum-sulfate to examine the effects of Al on lipid peroxidation in-vitro. The thiobarbituric-acid (TBA) assay was used to estimate tissue peroxidation. Tissue homogenates from 56 day old animals produced more TBA reactive substances than did homogenates from 1 day old animals. Al dependent peroxidation was only seen using 100 micrograms (microg) of Al in 1 day old chicks and 500microg Al in 56 day old chicks. Peroxidation was evident within 15 minutes of incubation and peaked at 30 minutes. Formation of TBA reactive substances using 1 millimolar Al showed a positive linear relationship with the protein concentration after 30 minutes of incubation. No changes in the body weights, brain weights, heights, endogenous levels of TBA reactive substances, free sulfhydryl levels, or brain protein content were seen in animals which ingested Al for 15 days. [Chainy GBN et al; Bull Environ Contam Toxicol 50 (1): 85-91 (1993)]

 

/LABORATORY ANIMALS: Neurotoxicity/ Oral administration of Al3+ to rats and chickens fed aluminum sulfate was believed to bind to ferritin and thus secondarily free more cellular Fe2+; such increased activity enhanced membrane lipid peroxidation activity, particularly in the brain. Such phenomena were believed to be related aluminum neurotoxicity. [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V2 377

  

/LABORATORY ANIMALS: Neurotoxicity/ We exposed male albino rats for 35 days to aluminum sulfate by gavage. ... Aluminum levels were high in brain specimens of the treated groups comparing to the control and it was dose-dependent. Marked increase in glutamate and glutamine levels was noticed while GABA level was significantly decreased.The most pronounced changes in brain tissue included spongioform changes in the neurons specially those of hippocampus, nuclear deformity, and neurofibrillary degeneration, similar to neurofibrillary tangles in Alzheimer's disease. [El-Rahman SS; Pharmacol Res 47 (3): 189-194 (2003)]

 

  /LABORATORY ANIMALS: Neurotoxicity/ ... Adult male Sprague-Dawley rats classified into different groups were given aluminum sulfate-dosed drinking water in the concentrations of 0%, 0.25%, 0.5% and 1%, respectively. After 30 days of aluminum treatment, the animals were subjected to spinal cord trauma. Laminectomy was performed at T7-8 in anesthetized rats, followed by placement of a compression plate (2.2 x 5 mm) loaded with a 35-g weight over the exposed spinal cord for 5 minutes. Control animals underwent the same surgical procedure, but the compression injury was not induced (sham). Postoperative neurological function was assessed using the inclined-plane test and by obtaining a modified Tarlov score and vocal/sensory score daily for 10 days. Electrophysiological changes were assessed using corticomotor evoked potentials, whereas pathological changes were assessed by light microscopy. The level of vitamin E in the spinal cord was measured as an index of antioxidant defense. The behavioral, biochemical, and histological analyses were performed in a blinded fashion. Analysis of results obtained in the behavioral studies revealed that the compression of spinal cord produced transient paraparesis in which a maximum motor deficit occurred at Day 1 following SCI and resolved over a period of 10 days. Administration of aluminum significantly impaired the recovery following SCI. Analysis of the results of the biochemical, electrophysiological, and histopathological studies also confirmed the deleterious effects of aluminum on recovery from SCI in rats. [Al Moutaery K et al; J Neurosurg 93 (2 Suppl): 276-282 (2000)]

 

   

/LABORATORY ANIMALS: Neurotoxicity/ Administration of aluminum sulfate in the drinking water of male Sprague-Dawley rats for thirty days resulted in an impairment of both consolidation and extinction of a passive avoidance task. No impairment of performance was observed on an active avoidance task, radial arm maze or open field activity measure. Biochemical analysis indicated a slight (less than 10%) but significant increase in hippocampal muscarinic receptor number after aluminum treatment as determined by tritiated quinuclidinyl benzilate (3H-QNB) binding. No changes were found in choline acetyltransferase (ChAT) activity, phosphoinositide hydrolysis, 3H-QNB binding in the cortex or tritiated pirenzepine (3H-PZ) binding in the hippocampus or cortex. These results indicate that cholinergic degeneration was not the cause of the observed cognitive impairments. [Connor DJ et al; Pharmacol Biochem Behav 31 (2): 467-474 (1988)]

Dermal exposure:

No studies were located regarding neurological effects in humans after acute- or intermediate-durationdermal exposure to various forms of aluminum.

Graves et al. (1990) examined the association betweenAlzheimer’s disease and the use of aluminum-containing antiperspirants in a case-control study using130 matched pairs. The Alzheimer’s disease was clinically diagnosed at two geriatric psychiatric centers;the controls were friends or nonblood relatives of the Alzheimer patients. Information on lifetime use ofantiperspirants/deodorant was collected via a telephone interview with the subject’s spouse. Noassociation was found between Alzheimer’s disease and antiperspirant/deodorant use, regardless ofaluminum content (odds ratio of 1.2; 95% confidence interval of 0.6–2.4). When only users of aluminumcontainingantiperspirants/deodorants were examined, the adjusted odds ratio was 1.6 (95% confidenceinterval of 1.04–2.4). A trend (p=0.03) toward a higher risk ofAlzheimer’s with increasing use ofaluminum-containing antiperspirants/ deodorants was also found.

Inhalation exposure:

No brain weight or histological changes were observed inFischer 344 rats or Hartley guinea pigs exposed by inhalation to up to 6.1 mg Al/m3 as aluminumchlorhydrate for 6 months (Steinhagen et al. 1978).

Groups of rats and guinea pigs were exposed, by inhalation, to 0.25, 2.5, and 25 mg/m3 of aluminum chlorhydrate (ACH) for six months to study the effects of a common component of antiperspirants. Similar groups of animals of both species exposed to clean air served as controls. The ACH was generated as a particulate dust using a Wright dust feed mechanism. After six months of exposure, animals were sacrificed. Decreases in body weight were seen in rats exposed to 25 mg/m3 of ACH. Marked increases in lung weights and significant increases in lung to body weight ratios were seen in rats and guinea pigs exposed to 25 mg/m3 of ACH. The lungs of all rats and guinea pigs showed significant dose-related increases in aluminum accumulation when exposed to either 0.25, 2.5, or 25 mg/m3 of ACH. The lungs of all rats and guinea pigs exposed to either 2.5 or 25 mg/m3 of ACH contained exposure-related granulomatous reactions characterized by giant vacuoled macrophages containing basophilic material in association with eosinophilic cellular debris.

 

Justification for classification or non-classification

There are conclusive but not suffcient data for the classification of substance Aluminium sulphate with regard to neurotoxicity.