P
Paraoxon Detoxification See A-Esterases.
Paraquat
Kevin N Baer
& 2005 Elsevier Inc. All rights reserved.
* CHEMICAL ABSTRACTS SERVICE REGISTRY NUMBER:
CAS 1910-42-5 (dichloride)
* SYNONYMS: Paraquat dichloride; Methyl viologen;
1,10 -Dimethyl-4,40 -bipyridinium ion; Gramoxone
* CHEMICAL/PHARMACEUTICAL/OTHER CLASS: Quater-
nary nitrogen (bis-pyridinium) compound
* CHEMICAL STRUCTURE:
CH3 +
N N+ CH3
Uses
Paraquat is used as a broad-spectrum herbicide on
weeds and grasses in agricultural and nonagricultural
areas. It is used as a desiccant on tomatoes, cotton,
beans, soybeans, potatoes, sunflowers, and sugar
cane to aid in harvesting and to induce resin soaking
on pine trees.
Exposure Routes and Pathways
Accidental or intentional ingestion is the most com-
mon route of exposure. Poisonings from inhalation
and dermal exposure have also occurred.
Toxicokinetics
Paraquat has low but rapid gastrointestinal absorp-
tion (5–10%) and low skin absorption. Peak plasma
concentrations occur in less than 2 h following
ingestion. Generally, paraquat is not metabolized to
any large extent. In animal studies, metabolites have
been detected in urine, possibly resulting from the
action of intestinal microflora. Paraquat is actively
transported to alveolar cells, where it is reduced to
form highly reactive free radicals. The volume of
distribution is large and has been estimated at
2.75 l kg
1. Paraquat tends to attain higher and
more prolonged levels in the lung. Clearance is rapid
by the kidneys with 80–90% of the dose excreted in
the urine after 6 h. The terminal half-life increases
from 12 to 120 h or longer as renal failure begins.
Mechanism of Toxicity
Paraquat produces lung damage by all routes of ex-
posure. Progressive and generalized proliferation of
fibrous connective tissue is observed in the pulmo-
nary alveoli where paraquat is selectively concen-
trated. The mechanisms of action result from a
metabolically catalyzed single electron oxidation/
reduction reaction resulting in NADPH depletion
and the generation of oxygen free radicals. For ex-
ample, superoxide radicals are formed and attack
unsaturated lipids of cell membranes. This in turn
produces lipid free radicals, resulting in membrane
damage and loss of the functional integrity of the
cell. In some animal models, paraquat leads to
damage of dopaminergic cells in the subtantia nigra
similar to that seen in Parkinson’s disease.
Acute and Short-Term Toxicity
(or Exposure)
Animal
Paraquat is highly toxic by inhalation. Particle sizes
used in agricultural practices (400–800 mm) limits
lower airway deposition, thereby lessening inhala-
tion hazard. Paraquat is moderately toxic by the oral
route and only slightly toxic by the dermal route.
Paraquat causes moderate to severe eye irritation and
minimal dermal irritation. The oral and dermal LD50
330 Paraquat
values reported in rats and mice range from about 20
to 150 mg kg
1.
Human
Paraquat may result in severe toxicity to all organ
systems and death within 24 h after ingestion, inha-
lation, and dermal exposure. The initial symptoms
after ingestion are burning in the mouth and throat
with vomiting and diarrhea and subsequent fluid and
electrolyte loss. Depending on the dose (460 ml),
esophageal perforation, renal failure, cardiac ar-
rhythmias, convulsions, and coma can occur. Early
death is usually due to hepatic and renal toxicities.
The lethal dose in humans is estimated to be
B40 mg kg
1.
Chronic Toxicity (or Exposure)
Animal
Subchronic exposure to paraquat led to pulmonary
damage. A rabbit dermal toxicity study noted
scabbing and inflammation when tested at the
two highest doses (2.6 and 6.0 mg kg
1 group).
Inhalation of small particles (o2mm in diameter)
resulted in pulmonary changes and lesions in the
larynx. Chronic exposure in dogs led to chronic
pneumonitis. Paraquat did not appear to be car-
cinogenic in two long-term studies in rats and in
mice. In developmental toxicity studies, paraquat
caused delayed or retarded ossification in the fore-
limb and hindlimb digits and posterior portion of the
skullat maternally toxic dosages only. Paraquat does
not appear to influence reproduction.
Human
Survivors of the initial poisoning or from poisonings
from as little as 10–15 ml of the concentrate often
develop a progressive pulmonary fibrosis associated
with dyspnea and pulmonary edema several days or
weeks after exposure. As a result, death is due to
asphyxia.
In Vitro Toxicity Data
Paraquat did not demonstrate mutagenic capacity.
Clinical Management
No specific treatment is known. All cases of paraquat
exposure should be managed as a potentially fatal
exposure. Basic life-support measures should be insti-
tuted; however, the administration of supplemental
oxygen is not advised. Treatment must be instituted
early, within 10 h after ingestion. Treatment involves
removal of paraquat from the alimentary tract by
gastric lavage and cathartics, prevention of further
absorption by Fuller’s earth (30% w/v), and removal
of absorbed paraquat by hemodialysis or hemoper-
fusion. Use of various drugs, such as D-propranolol,
prednisone, and vitamins E and C, has provided little
benefit.
Signs of toxicity in animals are similar to those
in humans. Paraquat has been shown to be muta-
genic, carcinogenic, and teratogenic in experimental
animals.
Environmental Fate
Paraquat is relatively immobile in soil. Paraquat
resists hydrolysis, photodegradation in water, and
microbial degradation under both aerobic and an-
aerobic conditions. Dissipation is primarily by ad-
sorption to organic material and clay particles. As
paraquat persists in clay soils, it may be found in
surface water from erosion. Since it binds so strongly
to clay particles, paraquat is not generally a ground-
water concern.
Ecotoxicology
Paraquat is practically nontoxic to honey bees, only
slightly toxic to fish, and moderately toxic to terres-
trial animals. Hazard for birds and mammals is
generally short lived after paraquat application.
Exposure Standards and Guidelines
The reference dose for paraquat is 0.0045 mg kg
1
day
1. The acceptable daily intake for paraquat is
0.004 mg kg
1 day
1 while the threshold limit value
is 0.1 mg m
3.
See also: Lipid Peroxidation; Pesticides; Pollution, Water;
Respiratory Tract.
Further Reading
Ecobichon DJ (2001) Toxic effects of pesticides. In: Klaas-
sen CD (ed.) Casarett and Doull’s Toxicology, 6th edn.,
pp. 763–810. New York: McGraw-Hill.
Lock EA and Wilks MF (2001) Paraquat. In: Krieger R
(ed.) Handbook of Pesticide Toxicology, 2nd edn., pp.
1559–1604. San Diego: Academic Press.