1. Toxicology laboratory analysis and human exposure to p-chloroaniline.
- Author
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Pizon AF, Schwartz AR, Shum LM, Rittenberger JC, Lower DR, Giannoutsos S, Virji MA, and Krasowski MD
- Subjects
- Abdominal Pain chemically induced, Acetanilides urine, Air Pollutants urine, Aniline Compounds urine, Antidotes therapeutic use, Bicarbonates blood, Cells, Cultured, Coma chemically induced, Cyanosis chemically induced, Dizziness chemically induced, Gas Chromatography-Mass Spectrometry, Hepatocytes drug effects, Hepatocytes enzymology, Humans, Male, Methemoglobin metabolism, Methemoglobinemia chemically induced, Methemoglobinemia drug therapy, Methylene Blue therapeutic use, Nausea chemically induced, Oximetry, Rifampin pharmacology, Tachycardia chemically induced, Young Adult, Air Pollutants poisoning, Aniline Compounds poisoning, Clinical Laboratory Techniques, Inhalation Exposure, Methemoglobinemia diagnosis, Occupational Exposure, Toxicology
- Abstract
Introduction: p-Chloroaniline is more potent at producing methemoglobin than aniline in animal models. This case highlights the clinical presentation of an inhalation exposure to p-chloroaniline and associated laboratory analysis. An in-vitro study evaluating the metabolism of p-chloroaniline in human hepatocytes was undertaken to evaluate the metabolic fate more closely., Case Presentation: A 20 year-old man was working at a chemical waste plant when he developed dizziness, abdominal pain, and nausea. The exam was remarkable for coma, tachycardia, cyanosis, and pulse oximetry of 75%. Arterial blood gases showed a pH 7.38, pCO(2) 41 mmHg, pO(2) 497 mmHg, bicarbonate 24 mEq/L and methemoglobin 69%. Methylene blue administration led to complete recovery without sequelae. p-Chloroaniline was later identified as the chemical involved. He denied direct contact with the chemical, but was not wearing a dust mask or respirator. GC/MS confirmed p-chloroaniline and metabolites in the patient's urine., Methods: Human hepatocytes were incubated with 100 microM p-chloroaniline for 24 hours, in both rifampicin- and vehicle only-treated cells. The cell culture medium was collected for GC/MS analysis for p-chloroaniline metabolites., Results: Similar to the patient sample, both p-chloroaniline and p-chloroacetanilide were identified by GC/MS in hepatocytes incubated with p-chloroaniline. Neither p-chloroaniline incubated in empty cell culture nor direct GC/MS injection of p-chloroaniline generated any p-chloroacetanilide via non-enzymatic degradation., Discussion/conclusion: The seemingly innocuous dermal and inhalation exposure to p-chloroaniline dust can lead to life-threatening methemoglobinemia. The diagnosis can be confirmed with GC/MS analysis of the patient's urine, searching for p-chloroaniline and its primary metabolite p-chloroacetanilide.
- Published
- 2009
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