Study of Cytotoxic Effects of Benzonitrile Pesticides

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The benzonitrile herbicides bromoxynil, chloroxynil, dichlobenil, and ioxynil have been used actively worldwide to control weeds in agriculture since 1970s.

Study of Cytotoxic Effects of Benzonitrile Pesticides

The benzonitrile herbicides bromoxynil, chloroxynil, dichlobenil, and ioxynil have been used actively worldwide to control weeds in agriculture since 1970s. Even though dichlobenil is prohibited in EU since 2008, studies addressing the fate of benzonitrile herbicides in the environment show that some metabolites of these herbicides are very persistent. We tested the cytotoxic effects of benzonitrile herbicides and their microbial metabolites using two human cell lines, Hep G2 and HEK293T, representing liver and kidneys as potential target organs in humans. The cell viability and proliferation were determined by MTT test and RTCA DP Analyzer system, respectively. The latter allows real-time monitoring of the effect of added substances. As the cytotoxic compounds could compromise cell membrane integrity, the lactate dehydrogenase test was performed as well. We observed high toxic effects of bromoxynil, chloroxynil, and ioxynil on both tested cell lines. In contrast, we determined only low inhibition of cell growth in presence of dichlobenil and microbial metabolites originating from the tested herbicides.

Every year about six thousand of tons of organic herbicides are deliberately introduced into the environment in order to prevent loss of cultural crops. This paper aims to evaluate the degree of hazard of the benzonitrile herbicides. Two substances of this herbicidal group, bromoxynil and ioxynil, are currently approved for commercial use in the European Union including the Czech Republic. Dichlobenil was prohibited as an herbicide by the European Union in the year 2008. Besides the high risks of dichlobenil used in granular form for aquatic environment and birds, one of the main reasons for the ban of the herbicide was the presence of high amounts of its metabolic product 2,6-dichlorobenzamide (BAM) generated by microorganisms. Most recently, these metabolites, in particular amides and acids of original substances, have been studied intensively because of their possible toxic effects.

Bromoxynil, chloroxynil, dichlobenil, and ioxynil are structurally similar members of the benzonitrile herbicides group. Except chloroxynil, they have been widely used in agriculture and households to control growth of weeds and their residues persist in the environment. The mechanism of toxic effects to target organisms was studied in detail in bromoxynil, dichlobenil, and ioxynil. Bromoxynil and ioxynil belong to the so-called mitochondrial uncouplers, which are relatively simple but very effective toxicants. Uncouplers generally act as protonophores which carry protons across the impermeable inner membrane of mitochondria by means of electrical and chemical gradients, which they are able to create. In addition to the fact that both herbicides damage the system of oxidative phosphorylation and inhibit mitochondrial activity, they were also found to inhibit the activity of chloroplasts. Dichlobenil is ranked among inhibitors of plant cell wall biosynthesis. Toxicity of the three used benzonitrile herbicides, bromoxynil, dichlobenil, and ioxynil, was tested in many prokaryotic and eukaryotic systems.