The most widely used pesticides in the world, herbicides are designed to kill plants and attack plant metabolic pathways that do not exist in humans and other animals. Therefore, in general, they have relatively low animal toxicity. There are hundreds of herbicides and herbicide mixtures on the market in the United States and throughout the world. Seven of the top 10 pesticide active ingredients (by amount used) are herbicides. Chlorophenoxy herbicides are plant growth regulators. They are commonly used for broadleaf weed control on cereal crops and pastures. Common chlorophenoxy herbicides include 2,4-D; Dicamba; and Silvex. Many products available to consumers include a mixture of salts in a petroleum base. Most toxicity from contact with skin or eyes or ingestion involves mucous membrane irritation. Very high dose exposure may result in neurological symptoms including muscle twitching, seizures, and coma. Renal and hepatic dysfunction may occur with large ingestions. Long-term health effects of low to moderate exposure include alleged, but not confirmed, carcinogenicity, teratogenicity, and reproductive abnormalities. Although no specific antidote is known, alkaline diuresis has been reported to be of value in severe overdose. Otherwise, aggressive supportive care including protection of the airway, correction of hypotension, and treatment of arrhythmias, hyperthermia, and seizures may be required (3).

Atrazine and glyphosate, triazine, and phosphonate herbicides are also widely used for weed control. Glyphosate was developed specifically as a much safer alternative to paraquat (discussed in a subsequent paragraph). Mucous membrane irritation is the most common adverse reaction to exposure to these chemicals and their many relatives. Gastrointestinal tract erosions were the primary adverse events in large-volume ingestions (all accidental or intentional), but renal, hepatic, central nervous system, and pulmonary involvement was sometimes noted. Since no antidote is known, supportive care is also indicated for these groups of agents (4,5).

Carbamate herbicides, unlike carbamate insecticides, do not produce inhibition of cholinesterase enzymes or the "all faucets on" cholinergic syndrome. Toxicity is uncommon. Common generic names for carbamate herbicides include asulam, terbucarb, butylate, pebulate, triallate, and thiobencarb. Mucous membrane irritation is the most common adverse effect. After removal of the chemical by soap and water, flushing the eyes, and increased fluid intake, treatment is supportive.

Urea-substituted herbicides are photosynthesis inhibitors, mainly used for weed control in noncrop areas. Chemicals in this class have names ending in "-uron" or "-oron"—e.g., chlorimuron, diuron, siduron, tebuthioron, and tetrafluoron. Urea-substituted herbicides have low systemic toxicity based on animal feeding studies; they may, however, produce methemoglobinemia with heavy ingestion. Methemoglobin and sulfhemoglobin levels should be measured in patients with dyspnea or cyanosis and a history of urea-substituted herbicide ingestion. Otherwise treatment of these ingestions is decontamination and supportive care.

The most dangerous group of herbicides is the bipyridyls. Paraquat is the most important of the bipyridyl group. Others in the group include diquat, chlormequat, and morfamquat. Bypyridyls exert their herbicidal activity by interfering with reduction of nicotinamide adenine dinucleotide phosphate (NADP) to reduced nicotinamide adenine dinucleotide phosphate (NADPH) during photosynthesis, producing superoxide, singlet oxygen, and hydroxyl and peroxide radicals. This eventually destroys lipid cell membranes, including those in the lungs, leading to late and irreversible pulmonary fibrosis. Major local effects of paraquat are due to its caustic properties. Corneal ulceration has been reported after paraquat concentrate was splashed in the eyes. Gastrointestinal tract ulceration including esophageal ulceration with perforation has occurred. After ingestion of >30 mg/kg of paraquat concentrate, pulmonary, cardiac, renal, and hepatic failure can occur within hours. Ingestion of 4 mL/kg or more may cause renal failure, resulting in impaired paraquat excretion and higher serum concentrations. Pulmonary involvement is the major target of ingested paraquat with an adult respiratory distress syndrome (ARDS)-like syndrome developing 1 to 2 days after ingestion, progressing to pulmonary fibrosis in a few days.

Treatment of paraquat ingestion is aimed at several points along the toxi-city pathway—removing toxin from the GI tract, increasing excretion from the blood, and preventing pulmonary damage with anti-inflammatory agents. Cautious aspiration with a nasogastric tube is appropriate if the patient presents within the first hour after ingestion. Because of the possibility of severe toxicity, some authorities still recommend activated charcoal (1 to 2 g/kg) if the patient is seen within 1 to 2 hours, repeated 4 hours later. Hemodialysis is effective for removing paraquat from the blood. Pulmonary damage is increased by oxygen supplementation, so low-oxygen breathing mixtures are recommended. Immunosuppression has been attempted with corticosteroids and cyclophosphamide or other similar agents, with limited success. Defer-oxamine and ^-acetylcysteine have been used as antioxidants. Prospective studies supporting immunosuppressive and antioxidant therapies are lacking. Diquat is felt to have much less pulmonary toxicity, but pulmonary fibrosis may also occur, especially if oxygen supplementation is used. Chlormequat toxicity resembles organophosphate toxicity but should not be treated as such (see the discussion of organophosphate pesticides in the next section). Treatment is by GI decontamination and supportive care. Morfamquat is rarely used. No human or animal toxicity has been reported with mor-famquat, but poisoning with the chemical should probably be treated initially as a paraquat poisoning (6).

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