Aluminium sulphate

Direct observations: clinical cases, poisoning incidents and other

Administrative data

Endpoint:

direct observations: clinical cases, poisoning incidents and other

Type of information:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Reliable with restrictions.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1998

Materials and methods

Study type:

clinical case study

Endpoint addressed:

repeated dose toxicity: oral

immunotoxicity

Test guideline

Qualifier:

according to guideline

Guideline:

other: osteomalacia due to antacid use associated with stainable bone aluminum in a patient with normal renal function.

Principles of method if other than guideline:

The patient consumed over 18 kg of elemental aluminum and 15 kg of elemental magnesium over 8 years of antacid use. This treatment resulted in the clinical syndrome of severe osteomalacia due to profound phosphate depletion. Treatment included withdrawing the antacid and supplementation with phosphate, calcium, and vitamin D.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Aluminium hydroxide

EC Number:

244-492-7

EC Name:

Aluminium hydroxide

Cas Number:

21645-51-2

IUPAC Name:

aluminum trihydroxide

Test material form:

solid: compact

Details on test material:

- Name of test material :aluminium hydroxide
- Molecular formula :Al(OH)3,
- Molecular weight :78.00 g/mol
- Smiles notation :[Al+3].[OH-].[OH-].[OH-]
- InChl :1/Al.3H2O/h;3*1H2/q+3;;;/p-3
- Structural formula attached as image file : see Fig.1
- Substance type: inorganic
- Physical state: White amorphous powder
- Density :2.42 g/cm³, solid
- Melting point: 300 °C, 573 K, 572 °F
- Solubility in water: 0.0001 g/100 mL (20 °C)
-Solubility: soluble in acids, alkalis, HCl, H2SO4
-Acidity (pKa) >7
-Flash point: Non-flammable

Method

Type of population:

other: A case of osteomalacia subsequent to chronic antacid use in a patient with normal renal function

Subjects:

The 39 year old female patient consumed approximately 70g of a commercial antacid daily for approximately 8 years, which is equivalent to consumption of over 18 kg of elemental aluminium. The daily dose ingested by this individual exceeded the manufacturer=s recommended maximum daily dose for this antacid. The patient developed severe osteomalacia due to phosphate depletion.

Ethical approval:

confirmed, but no further information available

Route of exposure:

oral

Reason of exposure:

intentional, occupational

Exposure assessment:

measured

Details on exposure:

The patient consumed over 18 kg of elemental aluminum and 15 kg of elemental magnesium over 8 years of antacid use. This treatment resulted in the clinical syndrome of severe osteomalacia due to profound phosphate depletion. Bone biopsy revealed stainable aluminum deposits along 27.6% of the total bone surface, which is a unique observation in a patient with normal renal function

Examinations:

This report concerns the case of a 39-year-old pharmacist who self-mediated for peptic ulcer disease with high doses of a potent antacid containing aluminum and magnesium hydroxide. The patient consumed over 18 kg of elemental aluminum and 15 kg of elemental magnesium over 8 years of antacid use. This treatment resulted in the clinical syndrome of severe osteomalacia due to profound phosphate depletion. Bone biopsy revealed stainable aluminum deposits along 27.6% of the total bone surface, which is a unique observation in a patient with normal renal function.

Medical treatment:

Treatment included withdrawing the antacid and supplementation with phosphate, calcium, and vitamin D. She experienced marked subjective and objective improvement with this regimen. This included a striking increase in her bone mineral density occurring over the 2-year follow-up period.

Results and discussion

Clinical signs:

The 39 year old female patient consumed approximately 70g of a commercial antacid daily for approximately 8 years, which is equivalent to consumption of over 18 kg of elemental aluminium. The patient developed severe osteomalacia due to phosphate depletion.

Results of examinations:

This case documents that long-term antacid therapy, even when used by patients with normal renal function and within the manufacturer's label recommendations, can lead to severe phosphate depletion, osteomalacia, and toxic accumulation of aluminum and magnesium.

Effectivity of medical treatment:

The clinical syndrome was readily treated by withdrawal of the antacid and with calcium and phosphate supplementation. Physicians recommending treatment with these compounds or learning of their patient's self-medication with them should inform the patient of the potential serious side effects these agents can cause when used chronically at maximally recommended doses.

Outcome of incidence:

The patient condition improved after cessation of antacid use and supplementation with calcium, phosphate and vitamin D.

Applicant's summary and conclusion

Conclusions:

This case documents that long-term antacid therapy, even when used by patients with normal renal function and within the manufacturer's label recommendations, can lead to severe phosphate depletion, osteomalacia, and toxic accumulation of aluminum and magnesium. This clinical syndrome was readily treated by withdrawal of the antacid and with calcium and phosphate supplementation. Physicians recommending treatment with these compounds or learning of their patient's self-medication with them should inform the patient of the potential serious side effects these agents can cause when used chronically at maximally recommended doses.

Executive summary:

Antacids containing aluminum and magnesium hydroxide are widely used nonprescription agents for treatment of gastritis and peptic ulcer disease. One of the side effects of these antacids is that they bind phosphate in the gut, resulting in its malabsorption. Short-term use, consistent with the directions on the manufacturer's label, is safe and effective for most patients. Heavy chronic use, even when within label, can cause serious skeletal impairment. This report concerns the case of a 39-year-old pharmacist who self-mediated for peptic ulcer disease with high doses of a potent antacid containing aluminum and magnesium hydroxide. The patient consumed over 18 kg of elemental aluminum and 15 kg of elemental magnesium over 8 years of antacid use. This treatment resulted in the clinical syndrome of severe osteomalacia due to profound phosphate depletion. Bone biopsy revealed stainable aluminum deposits along 27.6% of the total bone surface, which is a unique observation in a patient with normal renal function. Treatment included withdrawing the antacid and supplementation with phosphate, calcium, and vitamin D. She experienced marked subjective and objective improvement with this regimen. This included a striking increase in her bone mineral density occurring over the 2-year follow-up period.

This case documents that long-term antacid therapy, even when used by patients with normal renal function and within the manufacturer's label recommendations, can lead to severe phosphate depletion, osteomalacia, and toxic accumulation of aluminum and magnesium. This clinical syndrome was readily treated by withdrawal of the antacid and with calcium and phosphate supplementation. Physicians recommending treatment with these compounds or learning of their patient's self-medication with them should inform the patient of the potential serious side effects these agents can cause when used chronically at maximally recommended doses.