CHAPTER 2-123: PARAQUAT AND DIQUAT

INTRODUCTION

Paraquat dichloride (CAS # 1910-42-5) and diquat dibromide (CAS # 85-00-7) are dipyridyl herbicides used for weed control and as preharvest (desiccant) defoliants. Product formulations differ by country. In the United States, Syngenta currently markets Gramoxone Inteon (30.1% paraquat dichloride) and Reward (37.3% diquat dibromide). Other, less concentrated formulations of diquat are also marketed. Roundup QuikPro is a water-soluble granular formulation (73.3% glyphosate and 2.9% diquat). In the United States, paraquat poisonings greatly outnumber diquat poisonings.

MECHANISM OF TOXICITY

1. Paraquat and diquat are di-cations whose toxic effects are similar. Concentrated solutions (eg, >20%) may cause severe corrosive injury when ingested, injected, or applied to the skin, eyes, or mucous membranes. The dipyridyl herbicides are extremely potent systemic toxins and cause multiple-system organ damage. Engaging in a nicotinamide adenosine dinucleotide phosphate (NADPH)–powered reduction and oxidation cycle, dipyridyls spawn highly reactive free radicals, including superoxide and hydroxyl anions, leading to cell death and tissue destruction via lipid peroxidation. Renal failure is a common feature of both poisonings. Hepatic and cardiovascular failure may occur.

   1. In addition, paraquat is selectively taken up and concentrated by pulmonary alveolar cells, leading to cell necrosis followed (within days) by connective tissue proliferation and pulmonary fibrosis.

   2. Diquat is not taken up by pulmonary alveolar cells and does not cause pulmonary fibrosis, but it has been associated with CNS hemorrhagic infarctions.

2. Pharmacokinetics

   1. Absorption. Paraquat and diquat are rapidly (but incompletely) absorbed from the GI tract, and peak serum levels are reached within 2 hours of ingestion. The presence of food may reduce or delay absorption significantly. Although absorption is poor through intact skin, the dipyridyl herbicides can be taken up through abraded skin or after prolonged contact with concentrated solutions. Fatalities usually result from ingestion but have been reported after intramuscular injection, after vaginal and percutaneous exposure, and rarely after inhalation. Dipyridyls are contact herbicides not systemically incorporated into plants. Once applied to plants or soil, they are rapidly bound and unlikely to be toxic.

   2. Distribution. Paraquat has an apparent volume of distribution of 1.2–1.6 L/kg. It is taken up most avidly by lung, kidney, liver, and muscle tissue. In the lungs, paraquat is actively taken up against a concentration gradient.

   3. Elimination. Paraquat is eliminated renally, with more than 90% excreted unchanged within 12–24 hours if renal function is normal. Diquat is eliminated renally and via the GI tract.

TOXIC DOSE

Diquat is slightly less toxic than paraquat. However, this distinction may be of little comfort, as both compounds are extremely poisonous.

1. Paraquat. Ingestion of as little as 2–4 g, or 10–20 mL, of concentrated 20% paraquat solution has resulted in death. The estimated lethal dose of 20% paraquat is 10–20 mL for adults and 4–5 mL for children. The mean oral 50% lethal dose (LD₅₀) in monkeys is approximately 50 mg/kg.

2. Diquat. Diquat deaths have been reported after ...