Toxicology laboratory analysis and human exposure to p-chloroaniline.
BACKGROUND
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.


METHODS
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.


CONCLUSIONS
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.
Pizon
Anthony F
AF
Department of Emergency Medicine, University of Pittsburgh Medical Center, Pennsylvania, USA. pizonaf@upmc.edu
Schwartz
Anna R
AR
Shum
Leo M
LM
Rittenberger
Jon C
JC
Lower
Darla R
DR
Giannoutsos
Spiros
S
Virji
Mohamed A
MA
Krasowski
Matthew D
MD
D015746:Abdominal Pain / Q000139:chemically induced; D000083:Acetanilides / Q000652:urine; D000393:Air Pollutants / Q000506:poisoning* / Q000652:urine; D000814:Aniline Compounds / Q000506:poisoning* / Q000652:urine; D000931:Antidotes / Q000627:therapeutic use; D001639:Bicarbonates / Q000097:blood; D002478:Cells, Cultured; D019411:Clinical Laboratory Techniques; D003128:Coma / Q000139:chemically induced; D003490:Cyanosis / Q000139:chemically induced; D004244:Dizziness / Q000139:chemically induced; D008401:Gas Chromatography-Mass Spectrometry; D022781:Hepatocytes / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D019570:Inhalation Exposure; D008297:Male; D008706:Methemoglobin / Q000378:metabolism; D008708:Methemoglobinemia / Q000139:chemically induced / Q000175:diagnosis* / Q000188:drug therapy; D008751:Methylene Blue / Q000627:therapeutic use; D009325:Nausea / Q000139:chemically induced; D016273:Occupational Exposure; D010092:Oximetry; D012293:Rifampin / Q000494:pharmacology; D013610:Tachycardia / Q000139:chemically induced; D014116:Toxicology; D055815:Young Adult
D000083:Acetanilides; D000393:Air Pollutants; D000814:Aniline Compounds; D000931:Antidotes; D001639:Bicarbonates; C012241:4-chloroacetanilide; D008706:Methemoglobin; D008751:Methylene Blue; D012293:Rifampin; C004658:4-chloroaniline