PRINCIPLES OF TOXICOLOGY - Biology East Borneo

15.4 HERBICIDES 357ClClO CH 2 C OOHFigure 15.4 2,4-Dichlorophenoxyacetic acid (2,4-D).Bipyridyl Compounds—Paraquat and DiquatParaquat (1,1′-dimethyl-4,4′-dipyridylium) (see Fig. 15.5) and diquat (1,1′-ethylene-2,2′-bipyridylium) are bipyridylium herbicides, with common trade names including Gramoxone(paraquat) and Aquacide (diquat). A majority of reported cases of toxicity associated with bothparaquat and diquat are seen in cases of accidental or intentional (suicidal) ingestion, withparaquat having greater toxicity than diquat. An emetic and stenching agent, valeric acid, is addedto paraquat solutions.Paraquat poisoning (e.g., from suicide attempts) can lead to multiorgan toxicity (e.g., gastrointestinaltract, kidney, heart, and liver) including pulmonary fibrosis. Early deaths occurring afterintoxication with paraquat result from acute pulmonary edema, oliguric renal failure, and hepaticfailure. Deaths occurring one to three weeks following an intoxication episode are typically the resultof pulmonary fibrosis. Paraquat is not typically readily dermally absorbed, but reports of toxicityfollowing sufficient dermal absorption have been seen in individuals with skin abrasions or individualswith continued dermal exposure to paraquat. Sufficient dermal exposure to paraquat can also causedermal irritation, blistering, and ulceration. Similar irritant effects are seen in the esophagus andstomach of individuals swallowing paraquat. Paraquat concentrates in the lung, where its proposedmechanism of action leading to pulmonary fibrosis is that by which free radicals are generated leadingto lipid peroxidation. Pulmonary fibrosis, which can be fatal in cases with sufficient exposure, beginswithin 2 days to 2 weeks following paraquat exposure.Inhalation is not believed to be a toxic route of exposure. Aerosol paraquat droplets have beenmeasured as having diameters exceeding 5 µm, indicating that they do not reach the alveolarmembrane to cause either direct or systemic toxicity via inhalation. In two field trials in whichabsorption of paraquat was measured by urinary paraquat levels, systemic absorption wasapparently not significant. The authors of that study concluded that “ordinary care in personalhygiene is sufficient to prevent any hazard from surface injury or from systemic absorption.”Also, a recent study conducted on a group of 85 paraquat spraymen revealed no adverse health effects(aside from irritant-type effects), including no lung effects, attributable to long-term occupational useof this herbicide.ClCl2+H 3 C+ +N N CH 32 Cl –ClFigure 15.5 Pa ra qua t.