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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:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study meets generally accepted scientific principles

Data source

Reference
Reference Type:
publication
Title:
Epidemic of Pediatric Deaths From Acute Renal Failure Caused by Diethylene Glycol Poisoning
Author:
O'Brien
Year:
1998
Bibliographic source:
JAMA. 1998;279(15):1175-1180

Materials and methods

Study type:
other: Case-control study, cohort study, and laboratory toxicologic evaluation
Endpoint addressed:
acute toxicity: oral
Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Case-control study, cohort study, and laboratory toxicologic evaluation to investigate an outbreak of deaths among children from acute renal failure in Haiti to determine the etiology and institute control measures.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: not applicable

Method

Type of population:
general
Subjects:
- Haitian residents younger than 18 years with idiopathic anuria or severe oliguria for 24 hours or longer
Route of exposure:
oral
Reason of exposure:
accidental
Exposure assessment:
estimated
Details on exposure:
Contaminated pharmaceutical products (locally manufactured acetaminophen syrup).
Examinations:
Diethylene glycol (DEG) was detected in the contaminated syrups by several separate confirmatory analytical techniques.
The DEG dose per kilogram of body weight for individual patients was estimated by multiplying the percentage of DEG in bottles provided by the child's parent by the volume missing from the bottle and dividing by the weight of the child as documented in the hospital admission record. For children without a documented weight, we estimated age-appropriate weights by applying the median weight-for-age z score from children whose weight was documented.4 For children who reportedly shared the contaminated medication with another person, we assumed that the affected child consumed the entire quantity missing from the bottle. This method provides an estimate of the maximum possible dose ingested; the actual ingested dose could have been any amount less than the calculated dose.

Results and discussion

Clinical signs:
In the study 109 cases of acute renal failure among children were identified. The clinical syndrome included renal failure, hepatitis, pancreatitis, central nervous system impairment, coma, and death. Of 87 patients with follow-up information who remained in Haiti for treatment, 85 (98%) died; 3 (27%) of 11 patients transported to the United States for intensive care unit management died before hospital discharge.
Effectivity of medical treatment:
no data
Outcome of incidence:
A locally manufactured acetaminophen syrup was highly associated with disease (odds ratio, 52.7; 95% confidence interval, 15.2-197.2). Diethylene glycol (DEG) was found in patients' bottles in a median concentration of 14.4%. The median estimated toxic dose of DEG was 1.34 mL/kg (range, 0.22-4.42 mL/kg). Glycerin, a raw material imported to Haiti and used in the acetaminophen formulation, was contaminated with 24% DEG.

Any other information on results incl. tables

An epidemic of severe systemic toxicity and deaths from DEG-contaminated acetaminophen syrup occurred in Haiti.

Applicant's summary and conclusion