PRINCIPLES OF TOXICOLOGY

Cl
Cl
Bipyridyl Compounds—Paraquat and Diquat
O CH 2 C O
Paraquat (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 both
paraquat and diquat are seen in cases of accidental or intentional (suicidal) ingestion, with
paraquat having greater toxicity than diquat. An emetic and stenching agent, valeric acid, is added
to paraquat solutions.
Paraquat poisoning (e.g., from suicide attempts) can lead to multiorgan toxicity (e.g., gastrointestinal
tract, kidney, heart, and liver) including pulmonary fibrosis. Early deaths occurring after
intoxication with paraquat result from acute pulmonary edema, oliguric renal failure, and hepatic
failure. Deaths occurring one to three weeks following an intoxication episode are typically the result
of pulmonary fibrosis. Paraquat is not typically readily dermally absorbed, but reports of toxicity
following sufficient dermal absorption have been seen in individuals with skin abrasions or individuals
with continued dermal exposure to paraquat. Sufficient dermal exposure to paraquat can also cause
dermal irritation, blistering, and ulceration. Similar irritant effects are seen in the esophagus and
stomach of individuals swallowing paraquat. Paraquat concentrates in the lung, where its proposed
mechanism of action leading to pulmonary fibrosis is that by which free radicals are generated leading
to lipid peroxidation. Pulmonary fibrosis, which can be fatal in cases with sufficient exposure, begins
within 2 days to 2 weeks following paraquat exposure.
Inhalation is not believed to be a toxic route of exposure. Aerosol paraquat droplets have been
measured as having diameters exceeding 5 µm, indicating that they do not reach the alveolar
membrane to cause either direct or systemic toxicity via inhalation. In two field trials in which
absorption of paraquat was measured by urinary paraquat levels, systemic absorption was
apparently not significant. The authors of that study concluded that “ordinary care in personal
hygiene 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 use
of this herbicide.
H 3C
OH
Figure 15.4 2,4-Dichlorophenoxyacetic acid (2,4-D).
Cl Cl
+ +
N N CH3 Cl
Figure 15.5 Pa ra qua t.
15.4 HERBICIDES 357
2+
2 Cl –