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Human Parathion Poisoning

A Toxicokinetic Analysis

  • Review Article
  • Published:
Toxicological Reviews

Abstract

The mortality rate of suicidal parathion poisoning is particularly high, the onset of fulminant cholinergic signs, and the patients frequently present to the emergency physician with life-threatening symptoms. Despite this uniformity, subsequent clinical course differs significantly among patients, mostly not as a result of different delays in treatment or insufficiency of primary care. Probably, the differences depend on the amount of poison absorbed and/or the disposition of the active poison, paraoxon.

We followed the toxicokinetics of parathion and tried to quantify the actual poison load. To this end, we monitored parathion-intoxicated patients (patients requiring artificial ventilation) for plasma levels of parathion and paraoxon along with the activity of erythrocyte acetylcholinesterase and its reactivatability. Plasma obidoxime concentrations were followed as well as the cumulative urinary para-nitrophenol conjugate excretion as a measure of total poison load. All patients received a standard obidoxime scheme of a 250mg bolus dose intravenously, followed by continuous infusion with 750mg per 24 hours as long as reactivation could be expected (usually 1 week). All other treatment was instituted as judged by the physician. It was recommended to use atropine at low doses to achieve dry mucous membranes, no bronchoconstriction and no bradycardia. Usually 1–2 mg/h were sufficient.

Seven selected cases are presented exemplifying toxicokinetic peculiarities. All patients were severely intoxicated, while the amount of parathion absorbed varied widely (between 0.12 and 4.4g; lethal dose 0.02–0.1g) and was generally much lower than anticipated from the reports of relatives. It remains open whether the discrepancies between reports and findings were due to exaggeration or to effective decontamination (including spontaneous vomiting, gastric lavage and activated charcoal). Absorption of parathion from the gastrointestinal tract was sometimes retarded, up to 5 days, resulting in fluctuating plasma profiles. The volume of distribution at steady-state (Vdss) of parathion was around 20 L/kg. Post-mortem analysis in one patient revealed a 66-fold higher parathion concentration in fat tissue compared with plasma, 16 days after ingestion. Biotransformation of parathion varied widely and was severely retarded in one patient receiving fluconazole during worsening of renal function, while phenobarbital (phenobarbitone) sedation (two cases) had apparently no effect. The proportion of plasma parathion to paraoxon varied from 0.3–30, pointing also to varying paraoxon elimination, as illustrated by one case with particularly low paraoxonase-1 activity. Obidoxime was effective at paraoxon concentrations below 0.5μM, provided aging was not too advanced. This concentration correlated poorly with the parathion concentration or the poison load. The data are discussed in light of the pertinent literature.

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Notes

  1. The use of trade names is for product identification purposes only and does not imply endorsement.

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Acknowledgements

No sources of funding were used to assist in the preparation of this review. The authors have no conflicts of interest that are directly relevant to the content of this review.

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Authors and Affiliations

  1. Toxicological Department of II. Medical Clinic, Technical University of Munich, Klinikum rechts der Isar, Munich, Germany

    Florian Eyer, Michael Haberkorn, Norbert Felgenhauer & Thomas Zilker

  2. Walther-Straub-Institute of Pharmacology and Toxicology, Ludwig-Maximilians-University, Nussbaumstr. 26, Munich, D-80336, Germany

    Veronika Meischner, Daniela Kiderlen &  Peter Eyer

  3. Bundeswehr Institute of Pharmacology and Toxicology, Munich, Germany

    Horst Thiermann & Franz Worek

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  1. Florian Eyer
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  2. Veronika Meischner
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Eyer, F., Meischner, V., Kiderlen, D. et al. Human Parathion Poisoning. Toxicol Rev 22, 143–163 (2003). https://doi.org/10.2165/00139709-200322030-00003

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