More fun with pesticides: Here's some info on the infamous Paraquat and
Diquat, pesticides/herbicides, which can cause the symptoms outlined below,
and which are also chemically similar to our other favorite chemical, MPP+
(the derivative of MPTP, which caused pd in a number of young people who were
trying to home-brew some heroin-like drug, MTPP, and screwed up the process
and ended up with toxic MPTP).
Wendy T
********************
Subj: twitching - paraquat & diquat
Date: 95-06-29 17:43:56 EDT
From: [log in to unmask] (Tebay, Wendy)
To: [log in to unmask] (athome)
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Commercial Products
Paraquat and diquat are identified chemically as DIPYRIDYLS.
Paraquat is a synthetic nonselective contact herbicide, usually marketed as
the dichloride salt. Dimethyl sulfate salts are also produced. Liquid
technical products range from 20% to 50% concentration. Names of liquid
concentrates are: Ortho Paraquat CL, Ortho Paraquat Plus, Cekuquat,
Crisquat, Herbaxon, Herboxone, Dextrone, Esgram, Gramocil, Gramoxone,
Goldquat 276, Sweep, Osaquat Super, Gramonol, Toxer Total, Pillarxone,
Pillarquat. Paraquat is commonly formulated in combination with other
herbicides:
With diquat: Actor, Preeglone, Preglone, Priglone, Weedol (a 2.5% soluble
granule formulation).
With monolinuron: Gramonol
With diuron: Gramuron, Paracol, Totacol, Dexuron
With simazine: Terraklene, Pathclear
Diquat is usually prepared as the dibromide monohydrate salt, 20% to 25% in
liquid concentrates. Deiquat and reglon alternative common names.
Commercial products are: Ortho Diquat, Aquacide, Dextrone, Reglone, Reglox,
Weedtrine-D. Combinations with paraquat are listed above. Diquat is still
used as a water herbicide, but it is now applied as a dessicant and
terrestrial herbicide as well.
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Diquat
Diquat is somewhat less damaging to skin than paraquat, but irritant
effects may appear following dermal contamination with the concentrate.
There is probably significant absorption of diquat across abraded or
ulcerated skin.
Systemically absorbed diquat is not selectively concentrated in lung
tissue, as is paraquat, and pulmonary injury by diquat is less prominent.
However, diquat has severe toxic effects on the central nervous system that
are not typical of paraquat poisoning although brain injury has been
observed postmortem in some fatal paraquat poisonings. Renal damage is an
important feature of poisonings by both agents. The kidney is the principal
excretory pathway for diquat absorbed into the body.
Early symptoms of poisoning by ingested diquat are similar to those from
paraquat, reflecting its corrosive effect on tissues: burning pain in the
mouth, throat, chest, and abdomen. Intense nausea, vomiting, and diarrhea
are characteristic. If the dosage was small, these symptoms maybe delayed
1-2 days. Blood may appear in the vomitus and feces. Intestinal ileus, with
pooling of fluid in the gut, has characterized several human poisonings by
diquat. Dehydration, hypotension, and tachycardia may result and shock is a
common cause of death. Agitation, restlessness, disorientation, and
psychotic behavior have been early manifestations of some diquat
poisonings. Tonic-clonic seizures and coma may supervene. Proteinuria,
hematuria, and pyuria may progress to renal failure and azotemia.
Elevations of serum alkaline phosphatase, AST, ALT, and LDH reflect liver
injury. Jaundice may develop. If the patient survives several hours or
days, circulatory function may fail due to toxic myocardiopathy, or
broncho-pneumonia may develop.
Over the past decade, the great majority of poisonings by paraquat and
diquat have been caused by ingestion - with suicidal intent in most cases.
Nearly all of the few poisonings caused by occupational exposure have been
survived, but the mortality rate among persons who have swallowed paraquat
or diquat remains distressingly high (60%). Avoidance of this mortality
will probably have to rely on preventive strategies or on stopping
gastrointestinal absorption very soon after the toxicant has been ingested.
Even though intestinal absorption of dipyridyls is relatively slow, lethal
uptake by critical organs and tissues apparently occurs within 18 hours,
possibly within 6 hours, following ingestion of toxic quantities of
paraquat and diquat. Dipyridyls have large volumes of distribution. Once
distribution to tissues has occurred, measures to remove dipyridyls from
the blood are very inefficient in reducing the total body burden.
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Paraquat
Particularly in concentrated form, paraquat causes injury to tissues with
which it comes into contact. It leaves the skin of the hands dry and
fissured, sometimes resulting in loss of fingernails. Prolonged contact
with skin may cause blistering and ulceration, with subsequent absorption
of paraquat in sufficient dosage to cause systemic poisoning. Prolonged
inhalation of spray droplets may cause nosebleed. Eye contamination results
in severe conjunctivitis and sometimes protracted and even permanent
corneal opacification. When ingested in adequate dosage (see below),
paraquat has life-threatening effects on the gastrointestinal tract,
kidney, liver, heart, and other organs.
The first phase of systemic poisoning consists of swelling, edema, and
ulceration of the mucosal linings of the mouth, pharynx, esophagus,
stomach, and intestine. Centrizonal hepatocellular injury along with damage
to the proximal renal tubules, myocardium, and skeletal muscle (sometimes
including focal necrosis) are the main features of the second phase. The
nervous system and pancreas are affected in some cases. The third phase -
injury to the lung - usually becomes evident 2-14 days following ingestion,
although, in some cases, pulmonary edema has developed only a few hours
after paraquat has been swallowed. Paraquat is selectively concentrated in
lung tissue where it destroys lung parenchymal cells probably by generation
of free-radical oxygen and subsequent lipid peroxidation. Hemorrhage, edema
fluid, and leukocytes infiltrate the alveolar spaces, after which there is
rapid proliferation of fibroblasts. Severe impairment of gas exchange
causes death from anoxemia and tissue anoxia. Remarkably, essentially full
recovery of pulmonary function occurs following paraquat poisonings which
are survived. Although absorption across intact skin is slow, abraded or
eroded skin allows efficient absorption. Fatal poisonings are reported to
have occurred as a result of protracted dermal contamination by paraquat.
The effect of paraquat on renal tubule cells is more likely to be
reversible than the effect on lung tissue, but impaired renal function may
play a critical role in determining the outcome of paraquat poisoning.
Normal tubule cells actively secrete paraquat into the urine, clearing it
efficiently from the blood. However, high blood concentrations poison the
secretory mechanism and may destroy the cells. Because the kidney is almost
the exclusive route of paraquat elimination from body tissues, renal
failure fosters a buildup of tissue concentrations, including those in the
lung. Unfortunately, this pathogenetic sequence may occur in the first
several hours following paraquat ingestion, generating lethal
concentrations of paraquat in lung tissue before therapeutic measures to
limit absorption and enhance disposition have taken effect. It is probably
for this reason that methods for enhancing paraquat disposition several
hours following ingestion have had little influence on mortality.
The hepatic injury from paraquat may be severe enough to cause jaundice,
but hepatotoxicity is rarely a major determinant of clinical outcome.
Elevated alkaline phosphatase, AST, ALT, and LDH are indications of
hepatocellular insult; jaundice signifies more severe injury.
Early symptoms and signs of poisoning by ingested paraquat are burning in
the mouth, throat, chest, and upper abdomen, due to the corrosive effect of
paraquat on the mucosal lining. Giddiness, headache, fever, myalgia, and
diarrhea (sometimes bloody) occur. Pancreatitis may cause severe abdominal
pain. Proteinuria, hematuria, pyuria, and azotemia reflect renal injury.
Oliguria/anuria indicate acute tubular necrosis.
Progressive decline in arterial oxygen tension and CO diffusion capacity
commonly precede pulmonary symptomatology. Cough, dyspnea, and tachypnea
usually appear 2-4 days following paraquat ingestion, but may be delayed as
long as 14 days. Progressive cyanosis and air hunger reflect deteriorating
gas exchange in the damaged lung. Coma usually precedes death. In some
cases, the coughing up of frothy sputum (pulmonary edema) is the early and
principal manifestation of paraquat lung injury.
Clinical experience has offered a rough dose-effect scale on which to base
prognosis in cases of paraquat ingestion (J.A. Vale, et al., Human
Toxicology, 6:41-47, 1987):
I. Less than 20 mg paraquat ion per kg body weight (less than 7.5 ml of 20%
(w/v) paraquat concentrate). No symptoms, or only gastrointestinal symptoms
occur. Recovery is likely.
II. Twenty to 40 mg paraquat ion per kg body weight (7.5-15.0 ml of 20%
(w/v) paraquat concentrate). Gastrointestinal, renal, hepatic and pulmonary
damage by paraquat occurs. Pulmonary fibroplasia ensues. Death occurs in
most cases, but may be delayed 2-3 weeks.
III. More than 40 mg paraquat ion per kg body weight (more than 15.0 ml of
20% (w/v) paraquat concentrate). Multiple organ damage occurs as in class
II, but is more rapidly progressive. Often characterized by marked
ulceration of the oropharynx. Mortality is essentially 100% in 1-7 days.
Although much concern has been expressed about the effects of smoking
paraquat-contaminated marijuana, toxic effects by this mechanism have been
either rare or nonexistent. Most paraquat that contaminates marijuana is
pyrolyzed during smoking to dipyridyl. Dipyridyl is a product of combustion
of leaf material itself (including marijuana) and presents little toxic
hazard.
It is tragic that use of paraquat as a suicidal agent has increased in
recent years, particularly in Japan and also in developing countries.
Several strategies are being tested to reduce the frequency of these
occurrences: addition of emetics, stenching agents, gelling substances.
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Paraquat and Diquat
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Donald P. Morgan, M.D., Ph.D.
Commercial Products
Toxicology and Manifestations of Poisoning
Confirmation of Absorption
Treatment of EXTERNAL Poisoning
Treatment of Poisoning by INGESTION
