New Formulation of Paraquat: A Step Forward but in the Wrong Direction?

Abstract

Paraquat is a contact herbicide (one that kills plants by contact rather than being taken up in the roots and acting systemically) that is extensively used in agriculture, as it is fast-acting and non-persistent in the environment. It has, however, one major problem—its toxicity when ingested. The mechanisms of this toxicity are well understood and were described in detail over 20 years ago [1]. Paraquat is marketed for agricultural use as a concentrated solution, and in this form it is estimated that as little as a mouthful ingested is likely to be fatal. Blood levels of paraquat are indicative of outcome [2], but many patients have levels over 100 times the estimated lethal concentration, making treatment extremely difficult. In these patients, death may occur within a few hours from multi-organ toxicity. In less severe cases renal failure and gastrointestinal upset occur, resulting in death within two or three days if untreated. If these complications are managed by haemodialysis and fluid resuscitation, pulmonary fibrosis follows due to redox recycling (repetitive oxidation and reduction of the molecule, using up cellular energy) of paraquat in the lung. Death is then secondary to anoxia several days later; early oxygen treatment is thought to increase the risk of lung damage as it fuels the redox process. Twenty years ago it was clear that treatments for paraquat poisoning were ineffective and that new approaches to managing such poisoning were required [3]. In the intervening period, small-scale studies have suggested a potential role for immunosuppressants [4] in preventing death from lung injury, but the efficacy of this treatment remains in doubt [5]. Linked Research Article This Perspective discusses the following new study published in PLoS Medicine: Wilks MF, Fernando R, Ariyananda PL, Eddleston M, Berry DJ, et al. (2008) Improvement in survival after paraquat ingestion following introduction of a new formulation in Sri Lanka. PLoS Med 5(2): e49. doi:10.1371/journal.pmed.0050049 Martin Wilks and colleagues compared the outcome of paraquat self-poisoning with the standard formulation against a new formulation following its introduction into Sri Lanka.