Toxicology laboratory analysis and human exposure to p-chloroaniline.

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.

• Authors: Anthony F Pizon, Anna R Schwartz, Leo M Shum, Jon C Rittenberger, Darla R Lower, Spiros Giannoutsos, Mohamed A Virji, Matthew D Krasowski
• Journal: Clinical toxicology (Philadelphia, Pa.) (Clin Toxicol (Phila)) Vol. 47 Issue 2 Pg. 132-6 (Feb 2009) ISSN: 1556-9519 [Electronic] England
• PMID: 18608262 (Publication Type: Case Reports, Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Acetanilides
• Air Pollutants
• Aniline Compounds
• Antidotes
• Bicarbonates
• 4-chloroacetanilide
• Methemoglobin
• Methylene Blue
• Rifampin
• 4-chloroaniline

Topics

• Abdominal Pain (chemically induced)
• Acetanilides (urine)
• Air Pollutants (poisoning, urine)
• Aniline Compounds (poisoning, urine)
• Antidotes (therapeutic use)
• Bicarbonates (blood)
• Cells, Cultured
• Clinical Laboratory Techniques
• Coma (chemically induced)
• Cyanosis (chemically induced)
• Dizziness (chemically induced)
• Gas Chromatography-Mass Spectrometry
• Hepatocytes (drug effects, enzymology)
• Humans
• Inhalation Exposure
• Male
• Methemoglobin (metabolism)
• Methemoglobinemia (chemically induced, diagnosis, drug therapy)
• Methylene Blue (therapeutic use)
• Nausea (chemically induced)
• Occupational Exposure
• Oximetry
• Rifampin (pharmacology)
• Tachycardia (chemically induced)
• Toxicology
• Young Adult