Logo image
Toxicology laboratory analysis and human exposure to p-chloroaniline
Journal article   Open access   Peer reviewed

Toxicology laboratory analysis and human exposure to p-chloroaniline

Anthony F Pizon, Anna R Schwartz, Leo M Shum, Jon C Rittenberger, Darla R Lower, Spiros Giannoutsos, Mohamed A Virji and Matthew D Krasowski
Clinical toxicology (Philadelphia, Pa.), Vol.47(2), pp.132-136
02/2009
DOI: 10.1080/15563650801971390
PMCID: PMC2656391
PMID: 18608262
url
https://www.ncbi.nlm.nih.gov/pmc/articles/2656391View
Open Access

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, 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.

Details

Metrics

Logo image