Toxicology laboratory analysis and human exposure to p-chloroaniline

• Published in: Clinical toxicology (Philadelphia, Pa.) Vol. 47; no. 2; pp. 132 - 136
• Main Authors: Pizon, Anthony F., Schwartz, Anna R., Shum, Leo M., Rittenberger, Jon C., Lower, Darla R., Giannoutsos, Spiros, Virji, Mohamed A., Krasowski, Matthew D.
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA Informa UK Ltd 01-02-2009; Taylor & Francis
• Subjects: Abdominal Pain - chemically induced; Acetanilides - urine; Air Pollutants - poisoning; Air Pollutants - urine; Analytical; Anemias. Hemoglobinopathies; Aniline Compounds - poisoning; Aniline Compounds - urine; Antidotes - therapeutic use; Bicarbonates - blood; Biological and medical sciences; Cells, Cultured; Clinical Laboratory Techniques; Coma - chemically induced; Cyanosis - chemically induced; Diseases of red blood cells; Dizziness - chemically induced; Gas Chromatography-Mass Spectrometry; GC/MS; Hematologic and hematopoietic diseases; Hepatocytes - drug effects; Hepatocytes - enzymology; Humans; Inhalation Exposure; Male; Medical sciences; Methemoglobin - metabolism; Methemoglobinemia; Methemoglobinemia - chemically induced; Methemoglobinemia - diagnosis; Methemoglobinemia - drug therapy; Methylene Blue - therapeutic use; Nausea - chemically induced; Occupational accident; Occupational Exposure; Oximetry; p-Chloroaniline; Rifampin - pharmacology; Tachycardia - chemically induced; Toxicology; Young Adult; Human; Hemoglobinopathy; p-Chloroaniline; Biological marker; Hemopathy; Aniline derivatives; Occupational exposure; Gas chromatography; Occupational accident; Toxicological exploration; Laboratory investigations; Analytical; Poisoning; Diagnosis; Methemoglobinemia; Mass spectrometry; Occupational medicine; GC/MS
• ISSN: 1556-3650; 1556-9519
• DOI: 10.1080/15563650801971390

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, pCO2 41 mmHg, pO2 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 μM 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.