Risk Assessment of Different Routes of Exposure to Organophosphate Pesticide (Chlorpyrifos 40% Ec) using Animal Model

Abstract

The loss of crops due to pest, plant disease and competition from weeds is very high. To avert or remedy these losses, farmers now increasingly deploy pesticides in their agronomic practices. This research aimed at assessing the risk assessment of the different routes (oral and inhalation) of exposure to chlorpyrifos an organophosphate pesticide and measurement marker parameters of the organs susceptible to chlorpyrifos toxicity using animal model. A total of 64 male wistar rats were used for the experiment. The animals were divided into two groups for oral (36 rats) and inhalation (28 rats) routes of exposure. The oral experimental groups consists of 20 animals, divided into 4 groups of 5 animals each and the inhalation experimental groups consists of 16 animals divided into 4 groups of 4 animals each. The four experimental groups in both routes of exposure consist of 3 treatment groups and a control group. Acute toxicity studies and the median lethal dose were carried out using a modified method. Colorimetric Method was used to determine hepatotoxicity of aspartate amino transferase (AST), alanine amino transferase (ALT) and alkaline phosphatase (ALP). Standard methods were used to determine oxidative stress markers of lipid peroxidation, catalase activity and glutathione peroxidase activity. Immunoassay test kit was used to carry out the reproductive toxicity studies. Docking of the ligands was carried out using Autodock Vina. Standard formulae were used to estimate the risk assessment study. The results from the 24 hour acute toxicity studies revealed that oral exposure to pesticide gave a median lethal dose (LD50) of 155 mg/kg b.w. while inhalation exposure gave a median lethal concentration (LC50) of 1414 mg/kg b.w. for 60 minutes. The hepatotoxicity studies showed that oral exposure to Chlorview® led to a significant (p<0.05) increase in the activities of AST, ALT and ALP when compared to the control. Oxidative stress markers (GSH, MDA, CAT and GPx) show that the pesticide induced appreciable oxidative imbalance in the system. In oral exposure, there was a significant (p<0.05) increase in group 3 CAT activity when compared to control. The reproductive toxicity studies revealed that that oral exposure to pesticide led to a significant (p<0.05) increase in the testicular Cholesterol and a significant (p<0.05) decrease in testosterone and sperm count when compared to control. Molecular Docking Study shows the binding affinities of a standard ligand (Mevastatin) and chlorpyrifos docked against the binding site of β-keto acyl ACP synthase, HMG CoA synthase and the rate limiting enzyme in cholesterol synthesis pathway HMG CoA reductase revealed that chlorpyrifos potentiates the key enzymes resulting in cholesterol production. The risk assessment studies show a subchronic toxicity of chlorpyrifos at the dose of 15.5 mg/kg b.w of chlorpyrifos accumulation was recorded for oral exposure. This research concludes that exposure to pesticides can pose a reasonable risk to human health both through oral and inhalation routes of exposure which affect many biochemical processes.