Para-phenylenediamine (PPD) is a common chromophoric ingredient in oxidative hair-dyes. In some African countries like Sudan, Egypt and Morocco but also in India this chemical is used alone or in combination with colouring extracts like Henna for dyeing of the hair or the skin. Excessive dermal exposure to PPD mainly leads to the N-mono- and N,N′-diacetylated products (MAPPD, DAPPD) by N-acetyltransferase 1 and 2 (NAT1 and 2) catalyzed reactions. Metabolites and PPD are mainly excreted via renal clearance. Despite a low risk of intoxication when used in due form, there are numerous cases of acute intoxication in those countries every year. At the ENT Hospital - Khartoum (Sudan) alone more than 300 cases are reported every year (∼10% fatal), mostly caused by either an accidental or intended (suicidal) high systemic exposure to pure PPD. Intoxication leads to a severe clinical syndrome including laryngeal edema, rhabdomyolysis and subsequent renal failure, neurotoxicity and acute toxic hepatitis. To date, there is no defined clinical treatment or antidote available and treatment is largely supportive. Herein, we show the development of a quick on-site identification assay to facilitate differential diagnosis in the clinic and, more importantly, the implementation of an advanced analytical platform for future in-depth investigations of PPD intoxication and metabolism is described. The current work shows a sensitive (∼25 µM) wet chemistry assay, a validated MALDI-MS/MS and HPLC-UV assay for the determination of PPD and its metabolites in human urine. We show the feasibility of the methods for measuring PPD over a range of 50–1000 µM. The validation criteria included linearity, lower limit of quantification (LLOQ), accuracy and precision, recovery and stability. Finally, PPD concentrations were determined in clinical urine samples of cases of acute intoxication and the applied technique was expanded to identify MAPPD and DAPPD in the identical samples.
Introduction: Paraphenylene Diamine (PPD) is an aromatic amine not found in nature. It is used in a variety of industrial products and in different hair dye formulations. It is well known that PPD is an allergen that may cause contact dermatitis, erythematous urticarial papules and eczema in susceptible individuals. However, the major systemic problem occurs when it is ingested accidentally, for purposes of suicidal intent or during attempted murder. Information on the systemic effects and outcome of hair dye poisoning in children is limited. In this article we review the literature for PPD intoxication in children. Review: PPD intoxication is a major health problem in eastern Africa, particularly Sudan, and in Morocco. It is also common in the Indian subcontinent. In two large series from Morocco and Sudan, Children constituted 11.5% and 18% of affected individuals respectively. Acute poisoning by PPD causes characteristic severe angio-edema of the upper airway, often requiring tracheostomy, accompanied by a swollen, dry, hard and protruding tongue. PPD intoxication results in multisystem involvement and can cause rhabdomyolysis and acute kidney injury (AKI), flaccid paralysis, severe gastro-intestinal manifestations, cardiotoxicity and arrhythmias. This form of severe intoxication is fatal if not treated aggressively. There is no specific antidote and treatment is mainly supportive with renal replacement therapy commonly used in cases with AKI. Reported mortality rates range between 12-42%. Conclusion: PPD intoxication is a life threatening condition. Clinical outcomes rely on early recognition, prompt referral, and aggressive supportive treatment in collaboration with different specialties.
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