Characterization of Organophosphorus Compounds and Studies of Biochemical and Genetic Factors in Outcome of Acute Toxicity

Abstract

This study is unique in that a comprehensive analysis of biochemical and genetic parameters were performed in an acute OP poisoning cohort. Methods to identify and measure different OP compounds were established and utilized to assess the poison load in patients. Phenotypic and Genotypic variants in the PON1 enzyme which is involved in the metabolism of OP compounds ingested were carried out. Monocrotophos was the most common compound ingested in this group. Our study also examined monocrotophos toxicokinetics in humans, where the renal elimination half-life of monocrotophos was determined. Plasma and whole blood cholinesterases activity were inhibited to different extent after OP ingestion, but did not correlate with clinical outcome. Patients who consumed hydrophilic compounds had a poor prognosis and had an increased incidence of intermediate syndrome. Chronic exposure to OP compounds suppressed cholinesterases activity and may have resulted in elevation of pancreatic and liver enzymes, the mechanism by which needs to be explored. The PON1 status in the Tamil Nadu population in the Vellore area has been determined both by phenotypic expression and by genotype. This PON1 status has also been related to the ability of patients to detoxify ingested OP compounds. The Majority of the acute OP poisoning cases were young males. These patients presented with altered physiological parameters and neurological deficit Ten different OP compounds were found to be consumed by these patients. Unidentified OP agents were present in 17% of the patients. Monocrotophos, quinalphos and triazophos were the top three compounds encountered in this cohort. Overall mortality in acute OP poisoning was 12%. Increased requirement for atropine and an increased incidence of intermediate syndrome was seen in the hydrophilic OP group. Cholinesterases at admission were highly suppressed. AChE stayed suppressed longer but BChE levels slowly recovered. Elevation of pancreatic and liver enzymes was also seen in this chronic exposure group.