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Toxicological information

Direct observations: clinical cases, poisoning incidents and other

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Administrative data

Endpoint:
direct observations: clinical cases, poisoning incidents and other
Type of information:
experimental study
Adequacy of study:
other information
Study period:
1993
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1993

Materials and methods

Study type:
poisoning incident
Endpoint addressed:
acute toxicity: dermal
Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
A 57 year-old female with hemorrhagic cystisis and scleroderma received an accidental intravenous injection of approximately 400 ml of sterile 1% alum (NH4Al(SO4)2) in 0.9% NaCl (approximately 46 mg of elemental aluminum) intended for bladder irrigation.
The injection date was designated as "day 0".
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): alum (NH4Al(SO4)2)
- Substance type: no data
- Physical state: no data
- Analytical purity: no data
- Isomers composition: no data
- Purity test date: no data
- Lot/batch No.: no data
- Stability under test conditions: no data
- Storage condition of test material: no data

Method

Type of population:
not specified
Subjects:
- Number of subjects exposed: one
- Sex: female
- Age: 57 year-old
- Race: no data
- Demographic information: no data
- Known diseases: hemorrhagic cystitis and scleroderma
- Other: no data
Ethical approval:
not specified
Route of exposure:
other: intravenous injection
Reason of exposure:
accidental
Exposure assessment:
not specified
Details on exposure:
A 57 year-old female with hemorrhagic cystisis and scleroderma received an accidental intravenous injection of approximately 400 ml of sterile 1% alum (NH4Al(SO4)2) in 0.9% NaCl (approximately 46 mg of elemental aluminum) intended for bladder irrigation.
The injection date was designated as "day 0".
Four intravenous infusions of deferoxamine, 750-1000 mg each, were given on days 1, 5, 17 and 41.
Examinations:
- Urine analysis: yes
- Haematology: yes
- Lung function parameters: no
- Other: bone marrow biopsy
Medical treatment:
No data

Results and discussion

Clinical signs:
Within a few hours post injection with alum, the patient developed fever.
Results of examinations:
- Urine analysis:
There wa no renal functional impairment. Serum aluminum levels fell from 2043 µg/dL on day 1 to 311 µg/dL on day 4, and remained in the range 243-494 µg/dL from days 6-16 post exposure. Thereafter, a slower phase of aluminum clearance from serum occured from days 19-144, resulting in an aluminum concentration of 22.7 µg/dL at the end of this period (normal < 15.6 µg/dL).


- Haematology:
Within a few hours post injection with alum, the patient developed gross hemoglobinemia and transient hypophophatemia (phosphorus 0.7 mg/dL; normal 2.5-4.5 mg/dL). Her hemoglobin level fell from 12.0 g/dL (pre-injection) to 9.5 g/dL (day 6 post injection), and 2 units of packed erythrocytes were given by transfusion.
Reticulocytes were 5.5% on day 1 and fell to 0.5% by day 6 post exposure, despite moderate anemia.
A marrow biopsy specimen taken on day 30, and erythrocyte indices remained normal. Platelet concentrations fell progressively from 561 000/mm3 prior to injection to 165 000/mm3 on day 6 post injection, and recovered to pre-injection levels by day 14.
There was no evidence of disseminated intravascular coagulation, although reactive leukocytosis occured during hemolysis.

- Other:
Hepatotoxicity was indicated by elevated serum aspartate aminotransferase levels that were maximal on day 2 (405 U/L; normal 0-40 U/L), and fell to 193 U/L by day 14. The serum alkaline phosphatase level was maximally elevated on day 6 post exposure (311U/L; normal 40-136 U/L), and fell to 193 U/L by day 14. Concentrations of other hepatic enzymes were similarly elevated.
Effectivity of medical treatment:
Not applicable
Outcome of incidence:
No data

Any other information on results incl. tables

Eighteen months after the alum injection, there is no evidence of residual toxicity.

Applicant's summary and conclusion

Conclusions:
Intravenous injection of NH4Al(SO4)2 produced hemolytic anemia and hepatic injury similar to that previously reported with ingested NH4(SO4)2.
Executive summary:

A 57 year-old female with hemorrhagic cystisis and scleroderma received an accidental intravenous injection of approximately 400 ml of sterile 1% alum (NH4Al(SO4)2) in 0.9% NaCl (approximately 46 mg of elemental aluminum) intended for bladder irrigation.

The injection date was designated as "day 0".

Four intravenous infusions of deferoxamine, 750-1000 mg each, were given on days 1, 5, 17 and 41.

Intravenous injection of NH4Al(SO4)2 produced hemolytic anemia and hepatic injury similar to that previously reported with ingested NH4(SO4)2.

These effects may be related to protein precipitation by the ammonium uib abd/or to the known ability of aluminum to bind adenosine phosphates.

Hypophosphatemia could be explained by plasma phosphate complexing by aluminum.

Eighteen months after the alum injection, there is no evidence of residual toxicity. The biphasic curve of aluminum disappearance from serum is similar to that of many other intravenously injected heavy metals, and seemed unaffected by intravenous deferoxamine administration.