Pizon Anthony F, Schwartz Anna R, Shum Leo M, Rittenberger Jon C, Lower Darla R, Giannoutsos Spiros, Virji Mohamed A, Krasowski Matthew D
Department of Emergency Medicine, University of Pittsburgh Medical Center, Pennsylvania, USA.
Clin Toxicol (Phila). 2009 Feb;47(2):132-6. doi: 10.1080/15563650801971390.
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.
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.
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.
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.
在动物模型中，对氯苯胺比苯胺更易导致高铁血红蛋白的产生。本病例着重介绍了吸入对氯苯胺后的临床表现及相关实验室分析。为更深入评估对氯苯胺的代谢归宿，开展了一项评估其在人肝细胞中代谢情况的体外研究。
一名20岁男性在一家化学废物处理厂工作时，出现头晕、腹痛和恶心症状。检查发现患者昏迷、心动过速、发绀，脉搏血氧饱和度为75%。动脉血气分析显示pH值7.38，二氧化碳分压41mmHg，氧分压497mmHg，碳酸氢根24mEq/L，高铁血红蛋白69%。给予亚甲蓝治疗后患者完全康复，未留下后遗症。后来确定所涉化学物质为对氯苯胺。患者否认直接接触该化学品，但当时未佩戴防尘口罩或呼吸器。气相色谱/质谱联用仪（GC/MS）证实患者尿液中存在对氯苯胺及其代谢产物。
将人肝细胞分别与100微摩尔对氯苯胺一起孵育24小时，一组肝细胞用利福平处理，另一组仅用赋形剂处理。收集细胞培养基用于对氯苯胺代谢产物的GC/MS分析。
与患者样本类似，在用对氯苯胺孵育的肝细胞中，GC/MS鉴定出了对氯苯胺和对氯乙酰苯胺。在空细胞培养基中孵育的对氯苯胺以及直接进行GC/MS注射的对氯苯胺，均未通过非酶降解产生任何对氯乙酰苯胺。
讨论/结论：看似无害的对氯苯胺粉尘经皮肤和吸入接触可导致危及生命的高铁血红蛋白血症。通过对患者尿液进行GC/MS分析，寻找对氯苯胺及其主要代谢产物对氯乙酰苯胺，可确诊该病。
