Acute Human Lethal Toxicity of Agricultural Pesticides

Background: Agricultural pesticide poisoning is a major public health problem in the developing world, killing at least 250,000–370,000 people each year. Targeted pesticide restrictions in Sri Lanka over the last 20 years have reduced pesticide deaths by 50% without decreasing agricultural output. However, regulatory decisions have thus far not been based on the human toxicity of formulated agricultural pesticides but on the surrogate of rat toxicity using pure unformulated pesticides. We aimed to determine the relative human toxicity of formulated agricultural pesticides to improve the effectiveness of regulatory policy. Methods and Findings: We examined the case fatality of different agricultural pesticides in a prospective cohort of patients presenting with pesticide self-poisoning to two clinical trial centers from April 2002 to November 2008. Identification of the pesticide ingested was based on history or positive identification of the container. A single pesticide was ingested by 9,302 patients. A specific pesticide was identified in 7,461 patients; 1,841 ingested an unknown pesticide. In a subset of 808 patients, the history of ingestion was confirmed by laboratory analysis in 95% of patients. There was a large variation in case fatality between pesticides—from 0% to 42%. This marked variation in lethality was observed for compounds within the same chemical and/or WHO toxicity classification of pesticides and for those used for similar agricultural indications. Conclusion: The human data provided toxicity rankings for some pesticides that contrasted strongly with the WHO toxicity classification based on rat toxicity. Basing regulation on human toxicity will make pesticide poisoning less hazardous, preventing hundreds of thousands of deaths globally without compromising agricultural needs. Ongoing monitoring of patterns of use and clinical toxicity for new pesticides is needed to identify highly toxic pesticides in a timely manner. Please see later in the article for the Editors’ Summary. Citation: Dawson AH, Eddleston M, Senarathna L, Mohamed F, Gawarammana I, et al. (2010) Acute Human Lethal Toxicity of Agricultural Pesticides: A Prospective Cohort Study. PLoS Med 7(10): e1000357. doi:10.1371/journal.pmed. 1000357 Academic Editor: Mervyn Singer, University College London, United Kingdom Received March 23, 2009; Accepted September 15, 2010; Published October 26, 2010 Copyright: 2010 Dawson et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This study was supported by the South Asian Clinical Toxicology Research Collaboration, which is funded by the Wellcome Trust/National Health and Medical Research Council International Collaborative Research Grant GR071669MA. The study sponsor had no role in study design, data collection, data analysis, data interpretation, or writing of the report. Competing Interests: ME has received financial support to attend a scientific meeting of a study funded by Syngenta. NAB and AHD have received travel expenses from Syngenta (a manufacturer of paraquat and some other pesticides) to attend meetings of a scientific advisory group in relation to studies of new paraquat formulations. Abbreviations: CI, confidence interval; EPA, Environmental Protection Agency; FAO, Food and Agriculture Organization; IQR, interquartile range; OP, organophosphorus; OR, odds ratio; WHO, World Health Organization. * E-mail: adawson@sactrc.org . These authors contributed equally to this work PLoS Medicine | www.plosmedicine. org 1 October 2010 | Volume 7 | Issue 10 | e1000357