Paraquat has been previously used to destroy illicit marijuana plants. However, even if the plants are harvested and smoked shortly after spraying, there appears to be no risk associated with paraquat. Residues as high as 2264 ppm (average 331 ppm) were found in 3.6% of confiscated marijuana in the US in 1978 (Hall, 1995).

The temperatures generated by smoking paraquat-contaminated marijuana inactivate the paraquat. NO cases of pulmonary injury from smoking paraquat-contaminated marijuana have been documented (Hall, 1995).

In Sri Lanka, illicit alcohol is brewed by fermenting and distilling a solution of cane sugar and the drink is referred to as "kasippu". During fermentation various agents are added to alter its taste and potency. These additives are used in minute quantities to increase the effects of the brew. In 2005, 50 men were exposed to this brew with 5 fatalities reported secondary to paraquat contamination. Among those that died, the most common symptoms included: fever, headache, cough, dyspnea, abdominal pain, hepatomegaly, and alterations in lung function. At autopsy, the findings were consistent with fatal acute pneumonitis secondary to paraquat exposure (Beligaswatte et al, 2008).

Paraquat is available as colorless crystals (dichloride salt) or a yellow solid (bis(methyl sulfate) salt). It is soluble in water, odorless or with a faint ammonia-like odor. Paraquat ion (active) is liberated through the application of the dichloride and bis(methyl sulfate) salts in the commercial product (Budavari, 1996; Clayton & Clayton, 1994; Lewis, 1998; Harbison, 1998).

Technical products are available as liquids, with concentrations ranging from 20% to 50% (Morgan, 1993).

Paraquat is classified as a Restricted Use Pesticide by the Environmental Protection Agency and may be used only by commercial licensed users. Exceptions to the restriction include spot weed and grass control pressurized spray formulations containing 0.44% paraquat bis(methyl sulfate) and liquid fertilizers containing 0.025%, 0.03%, or 0.04% paraquat dichloride (EPA, 1986).

A low concentration paraquat product is available in Japan (Yoshioka et al, 1992). The new product is a mixture of 4.5% w/v paraquat ion and 4.5% w/v diquat ion.

A new paraquat formulation called GRAMOXONE INTEON has been created to limit toxicity following intentional or inadvertent ingestion by reducing the amount of paraquat absorbed from the gastrointestinal tract. The formulation works by the addition of a natural alginate that immediately gels when it reaches the stomach, and the amount of an emetic was also increased. This improves the efficacy of using emesis after the formulation has gelled in the stomach. In addition, magnesium sulphate (an osmotic purgative) has been added to speed the transport of any remaining product through the small intestine to minimize absorption. In an observational study, the survival rates following an INTEON ingestion were significantly better than the standard formulation (hazard ratio 0.73, 95% CI 0.60-0.89; p = 0.002). At 3 month follow-up, the number of cases alive in the INTEON group were 103 (35.6%) (n=289), as compared to 76 (25.6%) (n=297) in the standard formulation group (Wilks et al, 2008).

Internationally, paraquat is usually available as a solution of 200 grams of paraquat ion per liter; in the USA, formulations of 2 pounds per US gallon are common (Hall, 1995).

Paraquat is also available as granular or solid preparations (Hall, 1995).

Paraquat may be formulated with other herbicides, such as (Hall, 1995):

• Diquat
• Monolinuron
• Diuron
• Simazine
• Princip
• Atrazine
• Bladex
• Lasso
• Lexone
• Lorox
• Sencor

GASTROINTESTINAL: Nausea and vomiting are present almost immediately following ingestion. Corrosive injuries to the esophagus and stomach are common and perforations may occur.

CARDIOVASCULAR: Patients may develop hypotension due to massive fluid losses and cardiac dysrhythmias. Prolonged QT has also been reported.

HEPATIC: Hepatic failure due to centrilobular necrosis progresses over the first 24 to 48 hours.

RENAL: Renal failure due to acute tubular necrosis progresses rapidly over the ensuing 24 hours postingestion.

NEUROLOGIC: Patients may develop CNS depression (eg, lethargy, coma) and seizures with severe toxicity.

PULMONARY: The lungs are inordinately affected by paraquat toxicity due to transport of the toxin into pneumocytes. Patients develop progressive fibrosis and hypoxia over 2 to 4 weeks postingestion.

MILD TO MODERATE TOXICITY: Ingestion of a 20% solution, the most commonly available concentrated solution, is expected to cause caustic injury to the oral mucosa and esophagus. Nausea and vomiting are common. The patient may develop transient renal, hepatic and respiratory impairment. Symptoms usually resolve in patients with a mild exposure. Patients with moderate toxicity can develop permanent pulmonary injury.

SEVERE TOXICITY: Nearly all patients that develop severe paraquat toxicity have ingested concentrated forms of the herbicide. Patients may die in the first several days due to gastrointestinal perforations or multiorgan failure. Patients that survive the early phase of toxicity involving cardiovascular, hepatic, and renal systems develop pulmonary fibrosis and subsequent death over the following 2 to 4 weeks postingestion.

EARLY FINDINGS may include:

LATE FINDINGS may include:

DERMAL EXPOSURE: High concentrations may lead to corrosive injury to the dermis (blistering). Symptoms occur rapidly and may progress for 24 hours. Systemic toxicity due to dermal exposure through intact skin is uncommon. However, prolonged exposure to concentrated solutions can lead to skin damage and subsequent systemic absorption. INHALATION EXPOSURE: Significant pulmonary toxicity from inhalational exposures has not been reported. This is likely due to the large size of the paraquat droplets when sprayed. Patients may develop upper airway irritation or ulceration due to inhalational exposure. OCULAR EXPOSURE: Significant corrosive injury may progress for 24 hours. Corneal injury and protracted opacification of the cornea may result from exposure.

Only one of 13 patients with an SIPP of 10 to 50 survived, the rest died between 115 and 960 hours after ingestion of respiratory failure. This group had increased cardiac index, initially increased left ventricular stroke work index, decreased systemic vascular resistance, increased oxygen delivery index and oxygen consumption index, and increasing oxygen extraction ratio. All patients with an SIPP of less than 10 survived (Yamamoto et al, 2000).

Consider prehospital administration of activated charcoal as an aqueous slurry in patients with a potentially toxic ingestion who are awake and able to protect their airway. Activated charcoal is most effective when administered within one hour of ingestion. Administration in the prehospital setting has the potential to significantly decrease the time from toxin ingestion to activated charcoal administration, although it has not been shown to affect outcome (Alaspaa et al, 2005; Thakore & Murphy, 2002; Spiller & Rogers, 2002).

Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).

ADVERSE EFFECTS/CONTRAINDICATIONS

Act quickly. Remove contaminated clothing; wash skin, including hair and nails vigorously; do repeated soap washings. Leather absorbs pesticides, and should not be worn in the presence of pesticides. All contaminated leather should be discarded. Remove all contaminated clothing and isolate.

Exposed eyes should be irrigated with copious amounts of room temperature water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, an ophthalmologic examination should be performed. Paraquat may cause severe eye irritation, reaching its maximum in 12 to 24 hours post exposure. Healing may be slow, but recovery is usually complete.

Administer supplemental oxygen when arterial oxygen tension falls below 50 mm Hg and/or the patient is symptomatic with respiratory distress. Monitor pulmonary function in surviving victims to assess degree of residual fibrosis. The therapeutic value of steroids, colchicine, superoxide dismutase, propranolol, immunosuppressants, and fibrinolytic agents has been claimed, but not established.

Inducing emesis is not recommended. Gastric lavage is probably of benefit only if it can be done within one hour of ingestion, although some authors advocate its use up to 24 hours after ingestion. The potential benefit of paraquat removal by gastric lavage must be weighed against the potential for esophageal bleeding, perforation, and scarring.

Paraquat irreversibly binds to clays and activated charcoal. Administer activated charcoal or clay (Bentonite USP or Fuller's Earth).

Inhalation of nitric oxide to maintain tissue oxygenation at low FiO2's in anticipation of lung transplantation once all absorbed paraquat has been eliminated may hold some therapeutic promise, but has not been documented to be successful.

MILD TOXICITY: Ingestion of less than 20 mg paraquat ion per kg body weight (less than 7.5 mL of 20% [w/v] paraquat concentrate): No symptoms or mild GI effects; recovery likely (Reigart and Roberts, 1999).

MODERATE to SEVERE TOXICITY: 20 to 40 mg paraquat ion per kg body weight (7.5 to 15 mL of 20% [w/v] paraquat concentrate): Pulmonary fibroplasia develops. Death occurs in most cases, but may be delayed 2 to 3 weeks (Reigart and Roberts, 1999).

FATAL: Greater than 40 mg paraquat ion per kg body weight (more than 15 mL of 20% [w/v] paraquat concentrate): Multiple organ failure occurs; toxicity progresses rapidly. Mortality is essentially 100% in 1 to 7 days (Reigart and Roberts, 1999). Progressive gastrointestinal, renal, hepatic and pulmonary damage occurs very rapidly (Morgan, 1993)

An 81-year-old man was minimally sprayed on the leg with a paraquat pesticide and failed to remove the contaminated clothing until the following day. A small burn (approximately 4% of the total body surface area) on the leg was treated empirically with a topical steroid. Four days later the patient became short of breath, and was admitted with evidence of acute respiratory distress syndrome, leukocytosis, and acute renal failure. Despite care, respiratory function continued to deteriorate and the patient died two days later (Soloukides et al, 2007).

A 50-year-old crop-duster carrying a load of paraquat herbicide lost control of his plane and crashed. Extensive burns (37% of total body surface area) on the skin resulted in cutaneous paraquat absorption. Skin decontamination occurred approximately 9.5 hours after exposure. The patient had a paraquat blood level of 0.169 mg/mL (standard lethal dose at 16 hours is 0.16 mg/mL) 20 hours after injury. The patient died 4 days after exposure with acute renal failure and progressive respiratory failure (Gear et al, 2001).

Prolonged contact with dilute spray (5 g/L) after spillage or leakage from a knapsack sprayer was associated with a fatal outcome in one case (Athanaselis et al, 1983).

A fatality was reported following alleged insertion of a tampon, inadvertently soaked in paraquat, into the vagina for approximately 10 minutes; it was removed because of burning sensation (Ong & Glew, 1989). Concentration was not specified and serum paraquat concentration was not available. Postmortem examination findings were consistent with paraquat poisoning.

A 35-year-old woman intentionally injected 5 mL of a 24% (estimated dose of 1.2 g) paraquat solution into a superficial vein. Initial plasma paraquat concentration was 18 mcg/mL 5 hours after exposure with a urine paraquat level exceeding 50 mcg/mL. Following 2 consecutive sessions of hemoperfusion, her blood paraquat level was 6.4 mcg/mL (24 hours after exposure). However, progressive dyspnea developed, and the patient died on hospital day 4 of multiple organ failure (Hsu et al, 2003).

Intravenous injection of 4 mL of 20% paraquat (approximately 20 mg/kg) resulted in fatality from pulmonary dysfunction at 15 days after injection in a 21-year-old man (Fernandez et al, 1991).

GENERAL: Prudence requires that all cases of paraquat ingestion be treated as potentially fatal poisonings. Systemic absorption of paraquat in the course of ordinary occupational use is apparently minimal.

An adult died several days after ingesting 5 to 10 mL of paraquat concentrate. He presented to hospital 41 hours postingestion and died 4 days later (Tsatsakis et al, 1996).

In accidental ingestions, the minimum lethal dosage of paraquat is estimated to be 30 mg/kg (Harsanyi et al, 1987).

A 9-year-old boy died 17 days after drinking water from an empty bottle that had once contained paraquat concentrate (Fernando et al, 1990).

In a series of 10 paraquat poisonings in Crete, all patients who ingested more than 100 mL of paraquat solution died, although some were still alive at hospital presentation 7 to 8 hours after ingestion (Tsatsakis et al, 1996).

A 23-year-old man presented to a local ED after inadvertently ingesting a mouthful of paraquat 20% (about 6 to 10 g). On admission, his paraquat concentrations in serum and urine were 2.12 mg/L and 350 mg/L, respectively, indicating a lethal dose. Despite supportive care, including extracorporeal membrane oxygenation therapy, he developed respiratory failure due to pulmonary fibrosis. He later developed hemodynamic instability and multiorgan failure and died 32 days postingestion from cardiac failure with pulseless electrical activity. No paraquat was detected in postmortem tissue specimen (Bertram et al, 2013).

Nonoliguric acute renal failure and mildly elevated liver enzymes were reported, but resolved within 1 month. Pulmonary effects were minor and reversible, except for a low CO transfer factor which persisted for more than 1 year.

Two adults survived an ingestion of 30 to 40 mL and 80 to 100 mL of paraquat solution, respectively (Tsatsakis et al, 1996).

0.027 AGE + 0.022 INGESTED AMOUNT + 0.0002 WBC - 4.06

The survival rate of those who lived more than a week following ingestion of a paraquat-containing product was significantly (p less than 0.05) improved in the group ingesting the low concentration paraquat product (paraquat 4.5% w/v and diquat 4.5% w/v, 84.6% survived) when compared to the group ingesting the paraquat concentrate (20% v/v, 57.8% survived) (Yoshioka et al, 1992).

All of the deaths from the low concentration paraquat product (paraquat 4.5% and diquat 4.5%) were associated with suicidal intent (Yoshioka et al, 1992). No deaths occurred following accidental ingestion of the low concentration paraquat product.

C : Possible human carcinogen.

Slope Factor:

RfD: 4.5x10(-3) mg/kg-day

Unit Risk:

RfC:

Unit Risk:

Adopted Value

Adopted Value

Under Study

TWA: 0.1 mg/m(3) (resp)

STEL:

Ceiling:

Carcinogen Listing: (Not Listed) Not Listed

Skin Designation: [skin]

Note(s):

IDLH: 1 mg/m3

Note(s): Not Listed

8-hour TWA:

8-hour TWA:

8-hour TWA:

Only the statutory or final RQ is shown. For more information, see 40 CFR table 302.4.

10/10,000

Amount necessary to be covered by this standard. See 40 CFR 355.30.

Only the statutory or final RQ is shown. For more information, see 40 CFR table 302.4.

10/10,000

Amount necessary to be covered by this standard. See 40 CFR 355.30.

MEXICO:

ARGENTINA:

BRAZIL:

COLUMBIA:

CANADA:

UNITED STATES:

TEEL-0: The threshold concentration below which most people will experience no adverse health effects.

TEEL-1: The airborne concentration (expressed as ppm [parts per million] or mg/m(3) [milligrams per cubic meter]) of a substance above which it is predicted that the general population, including susceptible individuals, could experience notable discomfort, irritation, or certain asymptomatic, nonsensory effects. However, these effects are not disabling and are transient and reversible upon cessation of exposure.

TEEL-2: The airborne concentration (expressed as ppm or mg/m(3)) of a substance above which it is predicted that the general population, including susceptible individuals, could experience irreversible or other serious, long-lasting, adverse health effects or an impaired ability to escape.

TEEL-3: The airborne concentration (expressed as ppm or mg/m(3)) of a substance above which it is predicted that the general population, including susceptible individuals, could experience life-threatening adverse health effects or death.

TEEL-0: The threshold concentration below which most people will experience no adverse health effects.

TEEL-1: The airborne concentration (expressed as ppm [parts per million] or mg/m(3) [milligrams per cubic meter]) of a substance above which it is predicted that the general population, including susceptible individuals, could experience notable discomfort, irritation, or certain asymptomatic, nonsensory effects. However, these effects are not disabling and are transient and reversible upon cessation of exposure.

TEEL-2: The airborne concentration (expressed as ppm or mg/m(3)) of a substance above which it is predicted that the general population, including susceptible individuals, could experience irreversible or other serious, long-lasting, adverse health effects or an impaired ability to escape.

TEEL-3: The airborne concentration (expressed as ppm or mg/m(3)) of a substance above which it is predicted that the general population, including susceptible individuals, could experience life-threatening adverse health effects or death.

TEEL-0: The threshold concentration below which most people will experience no adverse health effects.

TEEL-1: The airborne concentration (expressed as ppm [parts per million] or mg/m(3) [milligrams per cubic meter]) of a substance above which it is predicted that the general population, including susceptible individuals, could experience notable discomfort, irritation, or certain asymptomatic, nonsensory effects. However, these effects are not disabling and are transient and reversible upon cessation of exposure.

TEEL-2: The airborne concentration (expressed as ppm or mg/m(3)) of a substance above which it is predicted that the general population, including susceptible individuals, could experience irreversible or other serious, long-lasting, adverse health effects or an impaired ability to escape.

TEEL-3: The airborne concentration (expressed as ppm or mg/m(3)) of a substance above which it is predicted that the general population, including susceptible individuals, could experience life-threatening adverse health effects or death.