Abstract
Following the 2011 ban on paraquat sales, Korea has witnessed a significant reduction in the mortality rate associated with acute pesticide poisoning. Traditionally, paraquat and diquat, alongside several highly toxic organophosphates, carbamates, and organochlorine insecticides, have been recognized as culprits in causing fatalities among patients with acute pesticide poisoning. However, despite global efforts to curtail the use of these highly toxic pesticides, certain pesticides still exhibit a level of lethality surpassing their established clinical toxicity profiles. Understanding the clinical progression of these pesticides is paramount for physicians and toxicologists, as it holds the potential to enhance patient prognoses in cases of acute poisoning. This review aims to address the persistence of highly lethal pesticides, which continue to pose a grave threat to victims of acute poisoning.
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Keywords: Insecticides; Herbicides; Poisoning; Mortality
Capsule Summary
What is already known
Despite global efforts to curtail the use of highly toxic pesticides, certain pesticides still exhibit a level of lethality surpassing their established clinical toxicity profiles.
What is new in the current study
Understanding the clinical progression of potentially lethal pesticides is paramount for physicians and toxicologists in order to enhance patient prognoses in cases of acute poisoning. This review would unveil the persistence of such highly lethal pesticides, which continue to pose a grave threat to victims of acute poisoning.
INTRODUCTION
Following the 2011 ban on paraquat sales, Korea witnessed a significant reduction in the mortality rate associated with acute pesticide poisoning [
1]. Traditionally, paraquat and diquat, alongside several highly toxic organophosphates, carbamates, and organochlorine insecticides, have been recognized as major causes of fatalities among patients with acute pesticide poisoning [
2,
3]. However, despite global efforts to curtail the use of highly toxic pesticides, certain pesticides still exhibit a level of lethality surpassing their established clinical toxicity profiles [
1–
6].
Understanding the clinical progression of acute poisoning with these pesticides is paramount for physicians and toxicologists in order to enhance patient care and improve the prognosis. This review aims to address the persistence of such highly lethal pesticides, which continue to pose a grave threat to victims of acute poisoning.
CHLORFENAPYR
Chlorfenapyr is an insecticide, derived from halogenated pyrroles produced by
Streptomyces spp. According to the US Environmental Protection Agency, toxicity categories for acute hazards of pesticide products, the acute toxicity of chlorfenapyr following ingestion is considered toxicity category I (mild toxicity) in mice (lethal dose [LD
50] of 45 mg/kg) and category II (moderate toxicity) in rats (LD
50 of 441 mg/kg) [
7,
8]. In humans, chlorfenapyr intoxication can be fatal and is associated with distinctive clinical and neuroradiological features [
9–
15].
Chlorfenapyr acts as a pro-insecticide that must undergo conversion through oxidative removal of the N-ethoxymethyl group by the microsomal monooxygenase system of target insects to produce the toxic metabolite tralopyril [
16]. Tralopyril, identified as the most toxic metabolite in animal studies, has an oral LD
50 of 27 mg/kg in male rats [
17]. Possessing both lipophilic and acidic properties, tralopyril exerts its lethal effects on insects and rodent cells by causing uncoupling of oxidative phosphorylation [
8,
18]. In insect studies, inhibition of microsomal monooxygenases by the specific inhibitor pyperonyl butoxide significantly reduces the potency of chlorfenapyr, but not tralopyril [
19,
20]. Animal studies indicate the detergents in pesticides may enhance gastrointestinal absorption of chlorfenapyr [
21]; however, knowledge regarding the most other aspects of the pharmacokinetics of chlorfenapyr and tralopyril in mammals remains limited.
Radiologically, the involvement of the entire white matter tract is a characteristic finding, consistent with previous reports [
9–
11]. Rats with chlorfenapyr intoxication revealed vacuolar myelinopathy and myelin sheath swelling [
7]. Similar pathological changes in myelin and white matter necrosis have been observed in autopsies of patients with toxic leukoencephalopathy [
11,
14]. These findings suggest that chlorfenapyr may damage the white matter of the central nervous system (CNS), resulting in neurological symptoms and signs such as blurred vision, optic neuropathy, urinary incontinence, altered mental status, seizure, and paraplegia [
10–
13].
Toxic symptoms and signs of acute chlorfenapyr poisoning include fever, diaphoresis, general fatigue, blurred vision, psychological effects, pancreatitis, and rhabdomyolysis [
10,
22–
25]. Following chlorfenapyr ingestion, patients typically exhibit self-limited vomiting, diarrhea, a subjective feeling of heat, and diaphoresis within 1 to 14 days post-exposure [
10,
26,
27]. Restlessness and confusion may appear 4 to 18 days after exposure [
25,
28,
29]. The appearance of high body temperature or hyperthermia (>39 °C) 5 to 19 days post-exposure,, often indicates a poor prognosis [
15,
30–
32]. Hence, heightened vigilance is essential in cases of hyperthermia (>39 °C) associated with acute chlorfenapyr poisoning, irrespective of the onset timing. The reported minimal lethal dose for oral administration was estimated to be 10 mL of 10% chlorfenapyr based on the poisoning of a 13-year-old girl, and the median time to death is reported to be 10 days (ranging from 5 to 20 days) [
26,
32,
33]. Notably, inhalation and skin contact exposure can also result in severe poisoning. For instance, a 55-year-old man involved in farming work developed fever and seizures shortly after spraying a diluted chlorfenapyr solution (125 mL at 10% in 500 L of water) and died 7 days later [
34]. A 49-year-old man developed various neurotoxic symptoms and signs beginning 1 day after exposure of the skin on the arms, chest, and abdomen to a 10% chlorfenapyr solution [
28]. Lee et al. [
35] reported a 74-year-old man passed away 12 days after self-injection with 20 mL of chlorfenapyr into his abdomen. The main toxic symptoms and signs and the progression clinical toxicity are summarized in
Fig. 1.
All personnel encountering patients exposed to chlorfenapyr should exercise caution given the potential for secondary poisoning. There are no well-established specific treatments for acute chlorfenapyr poisoning and conservative treatment should be tailored to the patient's symptoms and clinical signs. Basic detoxification and supportive measures, may include administering activated charcoal and, if necessary, performing gastric lavage. Regarding the management of significant hyperthermia, a standardized treatment protocol for effectively managing significant hyperthermia has not been explicitly reported. Muscle relaxants, such as benzodiazepines, and neuroleptic agents like chlorpromazine, have been utilized to mitigate shivering and act as a preventive measure against seizures; however, clinical trials demonstrating their efficacy are lacking. Dantrolene sodium has not proven effective in reducing core temperature. Although antipyretic agents theoretically hold promise in addressing the acute-phase reactant response, they have not been adequately evaluated for this purpose. Active cooling methods, encompassing cold packs or ice packs, cooling blankets, evaporative cooling, and intravenous cold saline, are considered potential strategies to facilitate temperature reduction. In exigent circumstances, the contemplation of therapeutic hypothermia (target temperature management) may also be warranted.
Extracorporeal removal methods may be considered due to the small molecular weight of chlorfenapyr (407.6 Da), allowing it to readily cross cellular membranes [
19,
20]. However, the lack of comprehensive data regarding other toxicokinetic parameters of chlorfenapyr in humans, such as protein binding, volume of distribution, and lipid solubility, hinders the use of extracorporeal removal methods. Nevertheless, the latest clinical reports indicate timely elimination of the toxicant and early organ-function support can significantly enhance the prognosis; intermittent hemodialysis (IHD) or continuous renal replacement therapy (CRRT) may therefore be undertaken at the attending physician’s discretion [
27,
36]. It is important for healthcare providers to recognize that while the clinical course among patients may vary, with potential occurrence of delayed toxic symptoms following the initial alleviation of acute poisoning symptoms, and all patients exposed to chlorfenapyr, even in cases of dermal exposure, carry a potential risk of a relentless course and mortality [
28]. Therefore, proactive treatment to prevent delayed toxic symptoms is strongly recommended, as is extended in-hospital observation of individuals with chlorfenapyr intoxication.
BENTAZONE
Bentazone is a selective contact herbicide and is classified as a moderately hazardous (class II) herbicide by the World Health Organization [
37,
38].
In a rat model, bentazone was rapidly absorbed and mostly excreted in the urine [
37]. An hour after its oral administration, it was distributed to the stomach, liver, kidneys, and heart of the rat, but not to the brain or spinal cord [
37,
38]. The substance was metabolized to 6-OH bentazone and 8-OH bentazone through hydroxylation [
38,
39]. The LD
50 was 1,100 mg/kg in rats and 2,918 mg/kg in pheasants [
38,
39]. Bentazone was rapidly absorbed in and distributed to the stomach, liver, kidneys, and heart. Limited information regarding the toxicokinetics of bentazone in humans suggests rapid and extensive absorption following oral administration, with significant excretion in the urine, primarily in its unchanged form [
37]. Although bentazone is not thought to easily cross the blood-brain barrier (BBB) in rats, neurological toxic signs and symptoms in acute bentazone poisoning suggest that it may do so after consumption of large amounts. Its mechanism of action in humans is unknown, although the clinical features of poisoning suggest that bentazone may uncouple oxidative phosphorylation. It is likely that co-formulants are responsible for some of the toxic effects of some products.
The toxic symptoms and signs of acute bentazone poisoning include sweating, hyperpyrexia, nausea, vomiting, diarrhea, abdominal pain, cough, tachypnea, dyspnea, apnea, tachycardia, mental change, neurological abnormalities including agitation, talking nonsense, and loss of consciousness, muscle rigidity, rigor mortis, and cardiac arrest [
39–
45]. Limb rigidity was a prominent feature in severely intoxicated patients. Limb rigidity, rhabdomyolysis, hyperpyrexia, and elevated levels of aspartate and alanine aminotransferase may lead to misdiagnosis of acute bentazone poisoning as neuroleptic malignant syndrome [
40]. Fatal cases involving liver failure, kidney injury, and muscle rigidity, often accompanied by failed or delayed airway access, have been reported [
39-
42]. Of note, the emerging pattern of acute bentazon poisoning indicates that the onset of symptoms may occur in less than 1 hour, with death occurring within as little as 2 hours. Jaw rigidity commonly occurs in such cases. The acute symptoms associated with acute bentazon poisoning may resemble those of malignant hyperthermia, suggesting that lethality from acute poisoning might be further delayed.
In the clinical course of acute bentazone poisoning, the following should be noted: (1) the occurrence of musculoskeletal rigidity; (2) a very rapid progression to deterioration in cases of severe, life-threatening poisoning; and (3) the development of jaw rigidity unresponsive to muscle relaxants in severely poisoned patients. The main toxic symptoms and signs and clinical progression are summarized in
Fig. 2.
All personnel encountering patients exposed to bentazone should exercise caution given the potential for secondary poisoning. If the patient seeks medical attention within 1 hour of ingestion, gastric lavage should be performed, and activated charcoal administered. Activated charcoal administration may be helpful for several hours after exposure. There is no specific antidote for acute bentazone poisoning. The management of acute bentazone poisoning is symptomatic and supportive. As illustrated in
Fig. 2, severe poisoning advances rapidly and is frequently accompanied by trismus. Thus, in scenarios where severe poisoning is anticipated, proactive preparation for airway management is crucial. Laboratory work-up and the electrocardiogram results should be monitored. While dantrolene sodium hasn't been commonly used in treating this type of poisoning, it could be administered if muscle rigidity is expected to worsen significantly. In cases of hypotension and loss of consciousness, fluid resuscitation with vasopressor administration and respiratory support, including endotracheal intubation are crucial. The muscle relaxant succinylcholine may be ineffective against muscle rigidity in acute bentazone poisoning; in such cases, cricothyroidotomy will be needed to keep the airway open [
44].
G-SH AND POEA
Glyphosate is a nonselective herbicide that inhibits the shikimic acid pathway and has been extensively used worldwide since its development in 1970 [
46]. It is mainly sold as Roundup (Bayer AG) [
47]. Glyphosate isopropylamine or ammonium salts are commonly used as active ingredients, and many products also contain polyoxyethylene amine (POEA) as one of the surfactants [
4,
48–
50]. POEA often leads to harm in individuals who have been poisoned in the acute poisoning In rodents, the oral LD
50 of glyphosate is greater than 5 g/kg [
50]. However, the LD
50 of POEA is 1 to 2 g/kg. Due to this toxicity, a notable aspect of acute glyphosate surfactant herbicide (G-SH) poisoning is that while toxicity symptoms caused by glyphosate alone are mild, the co-formulant POEA used as an adjuvant becomes the primary cause of intoxication injury [
51]. Therefore, it is important to determine whether the glyphosate formulation to which a patient was exposed included POEA in order to establish treatment options and prognosis [
48,
50,
51].
The mechanism of G-SH toxicity appears to be related to the absorption and decomposition of surfactants containing POEA. Ingestion of surfactants may result in hemodynamic changes with decreased total vascular resistance [
52].
Immediate medical attention is crucial in cases of suspected G-SH poisoning, as symptoms can escalate swiftly. The main toxic symptoms and signs and clinical progression are summarized in
Fig. 3 [
46,
53–
63].
Given the severity of toxicity progresses based on the extent of POEA absorption, it is conjectured that the degree of systemic toxicity is closely related to the prognosis of the patient with acute G-SH poisoning. Toxic signs such as acute kidney injury, hypotension, and severe metabolic acidosis reflect the worsening of severe poisoning, and require special attention in the management of G-SH toxicity [
62,
64].
Ingestion of a large amount of G-SH (>250 mL) and/or the presence of seizure, coma, hypotension, cardiac arrest, PaO
2 to fraction of inspired oxygen ratio less than 100, severe metabolic acidosis, acute kidney injury, and hyperkalemia suggest severe poisoning and a poor prognosis. Additionally, although not explicitly indicated in
Fig. 3, the prognosis for elderly patients is poor.
All personnel encountering patients exposed to G-SH-should exercise caution given the potential for secondary poisoning. If the ingested amount is more than one sip (0.5 mL/kg) of a typical product containing 41% or higher glyphosate concentration, it is necessary to observe the patient for a minimum of 24 hours [
53,
65]. If the patient seeks medical attention within 1 hour of ingestion, gastric lavage should be performed, and activated charcoal should be administered. Activated charcoal administration can be beneficial for several hours after exposure. There is no specific antidote for glyphosate poisoning. Therefore, treatment typically involves provision of supportive care, including supporting breathing and cardiac function, as well as administering medications to manage symptoms. Recently, intravenous lipid emulsion has emerged as a potential antidote for moderate to severe poisoning and may be administered at the attending physician's discretion [
66–
68]. The mortality rate varies among reported cases but generally falls within the range of 7.5% to 16.1% [
47,
53]. After active rescue, due to chemical injury, scar contractures frequently occur in both the esophagus and trachea, which will require reconstruction surgery [
69]. In cases involving a drop in blood pressure or loss of consciousness, essential measures include fluid resuscitation with vasopressor administration, and respiratory support, including endotracheal intubation. If renal function remains normal after ingestion, elimination through the kidneys is likely operative; however, in poisonings where a large amount of G-SH has been ingested, and/or acute kidney injury, moderate to severe metabolic acidosis, pulmonary edema, hyperkalemia, or severe cardiovascular dysfunction have occurred or are anticipated, extracorporeal removal methods such as IHD or CRRT or extracorporeal membrane oxygenation become necessary [
64,
70,
71]. When the ingestion is attributed to a product containing glyphosate potassium, there is an increased risk of hyperkalemia, necessitating monitoring of plasma potassium concentrations [
72]. Studies examining long-term complications or sequelae following recovery from acute poisoning are lacking, and caution is warranted regarding potential complications, including esophageal stricture, and cancer of the esophagus, kidneys, and liver, and the onset of degenerative neurological disorders.
GLUFOSINATE AMMONIUM HERBICIDE
Glufosinate ammonium is an herbicide commonly used to control weeds and unwanted vegetation. It works by inhibiting an enzyme that is crucial for plant growth, but it can also be harmful to humans if ingested, inhaled, or comes into contact with the skin or eyes.. The LD
50 in rats is 1.66 g/kg, In humans, the acute oral LD
50 is 1.6 to 1.8 mg/kg [
73]. Gastrointestinal absorption is relatively rapid, with peak blood concentrations achieved within one; however, the presence of surfactants increases absorption approximately 25% to 30% [
74]. The glufosinate ammonium herbicide (GAH) that is commercially available in Korea does not contain sodium polyoxyethylene alkyl ether sulfate as the surfactant [
4]. Over 90% of the absorbed compound is eliminated through the kidneys, and when renal function is maintained normally, approximately 97% of the compound is eliminated within 24 hours [
73–
75].
Gastrointestinal irritation and damage may occur due to the surfactants, and CNS toxicity is suspected to be attributed to N-methyl-D-aspartate (NMDA) receptor activation and a reduction in γ-aminobutyric acid (GABA) [
4,
76–
79]. Glufosinate ammonium is a compound with high hydrophilicity and high polarity, limiting permeation through the intact BBB [
74]; nonetheless, glufosinate has been detected in the brains of acute glufosinate poisoning patients at concentrations that are typically about one-third of the plasma concentration. When GAH is formulated with alkyl ether sulfate as a surfactant, caution is warranted because it can lead to significant hemodynamic changes, including vasodilation, and direct cardiac suppression at high concentrations, increasing the risk of cardiovascular complications [
80].
Toxic symptoms and signs of acute GAH poisoning can vary depending on the route and extent of exposure, but they may include nausea, vomiting, diarrhea, abdominal pain, difficulty breathing, dizziness, headache, and in severe cases, seizures, loss of consciousness, diabetic insipidus, and apnea [
81–
87]. Immediate medical attention is crucial when there is suspicion of acute moderate to severe GAH poisoning, as toxic symptoms and signs can rapidly worsen in severity. It should be noted that even in cases where patients with acute GAH poisoning present with an alert mental status or a normal Glasgow Coma Scale (GCS) result upon admission to the emergency department, severe poisoning or fatality remains a possibility. Brain lesions secondary to acute poisoning are commonly found in the splenium of the corpus callosum, bilateral posterior limbs of the internal capsule, bilateral cerebellar peduncles, bilateral cerebral peduncles of the midbrain, and the hippocampus.
Fig. 4 outlines the clinical progression of acute GAH poisoning.
In the process of GAH decomposition, ammonia is often produced, leading to elevated plasma ammonia concentrations in acute GAH poisoning cases. However, for CNS toxicity to occur in moderate to severe GAH poisoning, we believe that GAH or its metabolic byproducts must breach the BBB. Moderate to severe poisoning symptoms seem to emerge when GAH crosses the BBB due to overdose or other mechanisms. Predicting fatal CNS toxicity solely based on initial plasma ammonia levels measured upon the ED admission, except in cases with exceptionally high levels (at least >100 µg/dL), is challenging [
88]. Severe CNS toxicity symptoms and signs likely result from stimulation of NMDA receptors by GAH or related metabolic products that have crossed the BBB. Additionally, exceptionally high plasma ammonia levels upon the ED admission may indicate exposure to a large amount of GAH or suggest specificity in GAH metabolism. While an increase in blood ammonia levels upon the ED admission may suggest exposure to a certain degree of overdose, accurately predicting severe CNS toxicity is challenging. Given the diverse findings and perspectives on the influence of hyperammonemia in the development of neurological toxicity and its role in the progression and prognosis of acute GAH poisoning, the above information should be interpreted with caution. The main toxic symptoms and signs and the clinical progression are summarized in
Fig. 4 [
85,
86,
89–
94].
All personnel encountering patients exposed to GAH should exercise caution given the potential for secondary poisoning. If the patient seeks medical attention within 1 hour of ingestion, gastric lavage is performed, and activated charcoal should be administered. Administration of activated charcoal may be beneficial for several hours after exposure. There is no specific antidote for acute GAH poisoning. Therefore, treatment typically involves provision of supportive care, including supporting breathing and cardiac function, as well as administering medications to manage symptoms. In cases where hypotension, loss of consciousness, or breathing difficulty occurs, fluid resuscitation including the administration of vasopressors and inotropic agents, and respiratory support, which includes endotracheal intubation, is necessary. At the discretion of the attending physician, IHD or CRRT may be administered in the early stages of acute poisoning to reduce plasma GAH concentrations [
95]. However, the effectiveness of these interventions in preventing severe complications, such as seizures and respiratory arrest, remains uncertain [
82,
95,
96]. Considering that the renal clearance of glufosinate ammonium is 1.6 to 1.8 times larger than that of extracorporeal elimination, it is recommended to limit extracorporeal elimination to patients experiencing the early phase of serious toxic symptoms or those with acute kidney injury. To date, there is no evidence supporting the administration of intravenous lipid emulsion as a therapeutic agent in cases of acute GAH poisoning.
Plasma ammonia concentrations should be assessed in acute GAH poisoning at admission and thereafter to monitor patient status, although the clinician should be aware they may not accurately reflect CNS ammonia concentrations or CNS symptoms [
79,
88,
97–
100]. Early symptoms or ammonia test results have limitations in predicting severity in cases of acute GAH poisoning [
101]. Hence, closely monitoring patients for at least 48 hours after GAH exposure appears essential. Clear treatment guidelines for managing hyperammonemia in patients with acute GAH poisoning have not been reported. However, given that elevated ammonia levels can lead to changes in consciousness, cognitive function, ataxia, seizures, and even coma, treatment is deemed necessary. Nonabsorbable disaccharides (such as lactulose, composed of the monosaccharides fructose and galactose) are considered the primary therapeutic approach for hyperammonemia. Rifaximin has emerged as the most effective antibiotic for hyperammonemia treatment due to its safety, efficacy, and tolerability. Additionally, sodium benzoate contributes to reducing blood ammonium levels by inhibiting glycine metabolism in the liver, kidney, and brain. Recovery from an acute poisoned state to everyday life may be prolonged. While few studies addressing long-term complications or sequelae following recovery from acute GAH poisoning are available, caution is warranted regarding potential complications, including reversible amnesia, prolonged overall cognitive dysfunction, psychotic features, and other neurolopsychological sequelae.
OTHER PESTICIDES
The following substances in Korea have been discontinued due to their high fatality in cases of acute poisoning, but they continue to be used due to their efficient functionality as pesticides. Therefore, proper disposal and handling of existing stocks are crucial to prevent accidental exposure.
Methomyl
Methomyl is a highly toxic carbamate insecticide commonly used to control a wide range of insects on crops, vegetables, and ornamental plants. It is known for its rapid action against pests, making it effective but also potentially dangerous to humans and other nontarget organisms. Regarding acute methomyl poisoning, it is important to note that liquid formulations may contain methanol as a surfactant [
102]. The possible rapid onset of severe symptoms, such as altered consciousness, requires close monitoring of exposed patients. In Korea, sales and distribution of methomyl were discontinued in 2012; however, products containing thiocarb, which can be metabolized into methomyl, are still available in the market, often mixed with other insecticidal compounds.
Mechanism of toxicity
Methomyl reversibly inhibits acetylcholinesterase, an enzyme that plays a crucial role in the nervous system by breaking down the neurotransmitter acetylcholine. When acetylcholinesterase is inhibited, acetylcholine accumulates in the synapses of cholinergic neurons, leading to cholinergic overstimulation [
103]. This can result in a range of symptoms affecting various bodily functions.
Clinical features
Exposure to methomyl can lead to a variety of symptoms, which can vary depending on the level of exposure and the route of exposure (ingestion, inhalation, or skin contact). The symptoms and signs of acute methomyl poisoning are represented in the mnemonic DUMBELS (diarrhea, urination, meiosis, bronchorrhea/bronchospasm, emesis/nausea, lacrimation, and salivation) [
103,
104]. Additional toxic symptoms and signs included profound sweating, dyspnea, headache, dizziness, muscle weakness, tremor, and confusion. In moderate to severe poisoning, breathing difficulties, mental change, and hypotension are characteristic features [
103–
105]. In rare instances, patients with acute methomyl poisoning did not manifest DUMBELS symptoms, emphasizing the need for caution among treating physicians.
Management
All personnel encountering patients exposed to methomyl should exercise caution given the potential for secondary poisoning. Decontamination methods such as gastric lavage or administration of activated charcoal may be used to reduce absorption. The treatment of acute methomyl poisoning involves supportive care and atropine administration to counteract the effects of excess acetylcholine if DUMBELS are identified [
103,
105]. When toxic symptoms and signs are vague, the atropine challenge test can be useful to identify the class of toxicant and evaluate the severity of poisoning. While the administration of pralidoxime (2-PAM) or obidoxime is not typically recommended for acute methomyl poisoning, in instances of prolonged cholinesterase inhibition 2-PAM is warranted, following a similar approach as in acute organophosphate poisoning [
106]. In cases of severe respiratory distress, patients may require oxygen supplementation or mechanical ventilation. Additional medications may be indicated to manage specific symptoms such as seizures or muscle tremors. Furthermore, in the event of a rapid decline in mental status and severe metabolic acidosis, it may be necessary to initiate treatment for concurrent acute methanol poisoning [
107].
Endosulfan, a highly toxic organochlorine insecticide and acaricide, was commonly used to control a variety of pests on crops like fruits, vegetables, and cotton. However, due to its high toxicity, persistence in the environment, and potential to accumulate in organisms, many countries have restricted or banned its use. Therefore, incidents of acute endosulfan poisoning have decreased.
Mechanism of action
Endosulfan acts on the nervous system by affecting the normal function of the neurotransmitter GABA. GABA is the major inhibitory neurotransmitter in the CNS [
108,
109]. Endosulfan inhibits GABA receptors, leading to overstimulation of nerve cells and various physiological effects [
108,
109].
Clinical features
Exposure to endosulfan can lead to a range of symptoms, which may vary depending on the level and route of exposure (ingestion, inhalation, or skin contact). Symptoms of acute endosulfan poisoning may include the following [
4,
109–
113]:
(1) Neurological effects: CNS symptoms are common and can include headache, dizziness, confusion, agitation, tremors, and intractable convulsions (seizures).
(2) Gastrointestinal distress: Nausea, vomiting, abdominal pain, and diarrhea are common gastrointestinal symptoms associated with endosulfan poisoning.
(3) Respiratory effects: Breathing difficulties, chest tightness, coughing, and wheezing can occur due to effect on the nervous system and respiratory muscles.
(4) Skin and eye irritation: Skin contact with endosulfan can cause irritation, redness, and itching. Eye exposure can lead to eye irritation and redness.
(5) Cardiovascular effects: Rapid heart rate (tachycardia) and hypotension may occur due to pulmonary embolism.
(6) Miosis: Constricted pupils can be a sign of endosulfan poisoning.
Management
All personnel encountering patients exposed to endosulfan should exercise caution given the potential for secondary poisoning. There is no specific antidote for acute endosulfan poisoning. The treatment of acute endosulfan poisoning involves provision of immediate medical attention and supportive care and may include the following:
(1) Decontamination: If the exposure is recent, decontamination methods such as washing the skin and eyes thoroughly or removing contaminated clothing can help reduce exposure.
(1) Symptomatic treatment: Medications can be prescribed to manage specific symptoms like seizures or respiratory distress.
(2) Respiratory support: In cases of severe respiratory distress, patients may require oxygen supplementation or mechanical ventilation.
(3) Vigilant monitoring: Patients exposed to endosulfan should be closely monitored for the development of symptoms and complications.
While seizures associated with acute endosulfan poisoning can occur for up to approximately 24 hours [
114,
115], the prognosis is generally more favorable compared to seizures resulting from other neurological diseases [
115]. Seizure management, including intravenous administration of lorazepam and antiepileptic agents, and continuous electroencephalogram monitoring is deemed necessary in cases of endosulfan-related status epilepticus [
115,
116].
CONCLUSION
The continued use of highly toxic pesticides, such as chlorfenapyr, bentazone, G-SH, and GAH, in agricultural practices poses a continuous risk of acute pesticide poisoning. These compounds exhibit multiple mechanisms of toxicity and clinical manifestations, necessitating early recognition, supportive care, and appropriate management. It is highly advantageous for physicians and health providers to possess knowledge about the clinical course of these pesticides, as this understanding can substantially enhance the provision of effective treatment and ultimately lead to improved patient outcomes.
NOTES
-
Author contributions
Conceptualization: SC; Formal analysis: SC, GWK; Investigation: GWK, HL; Methodology: SC; Supervision: SC, HL; Validation: GWK, SC; Visualization: SC; Writing–original draft: SC; Writing–review & editing: all authors. All authors read and approved the final manuscript.
-
Conflicts of interest
The authors have no conflicts of interest to declare.
-
Funding
The authors received no financial support for this study.
-
Data availability
Data sharing is not applicable as no new data were created or analyzed in this study.
Fig. 1.Clinical course of acute chlorfenapyr poisoning. In the clinical course of acute chlorfenapyr poisoning, the following should be noted: (1) the potential for fatality even with minimal exposure; (2) the possibility of “life-threatening delayed injury” occurring after the resolution of nonspecific acute poisoning; and (3) the extension of this “latent period” to approximately 14 days post-exposure.
Fig. 2.Clinical course of acute bentazone poisoning. In the clinical course of acute bentazone poisoning, the following should be noted: (1) the occurrence of musculoskeletal rigidity; (2) a very rapid progression to deterioration in cases of severe, life-threatening poisoning; and (3) the development of jaw rigidity unresponsive to muscle relaxants in severely poisoned patients. CNS, central nervous system.
Fig. 3.Clinical progression of acute glyphosate surfactant herbicide (G-SH) poisoning. The symptoms and signs of acute G-SH poisoning vary depending on the type and level of exposure, but may include involvement of the following: (1) gastrointestinal system (oropharyngeal irritation and nausea, vomiting, abdominal irritation and pain, diarrhea, hemorrhagic gastritis, elevated hepatic enzyme, esophageal perforation, and pyloric stenosis); (2) pulmonary system (dyspnea, pulmonary congestion, pulmonary edema, and aspiration pneumonia; (3) cardiovascular system (hypotension, shock, first-degree heart block, ST-T wave change, and cardiac arrest); (4) renal system (oliguria and acute kidney injury; and (5) other organs/functions (skin irritation, hyperkalemia, hemolysis, mental change, seizures, and coma in severe cases). CNS, central nervous system; FiO2, fraction of inspired oxygen; AKI, acute kidney injury.
Fig. 4.Clinical progression of acute glufosinate ammonium herbicide (GAH) poisoning. In the clinical course of acute GAH poisoning, the following should be noted: (1) plasma ammonia concentrations are frequently elevated beginning in the early phase of poisoning; (2) various neurotoxic symptoms and signs necessitating critical care support may be present in moderate to severe poisoning; and (3) the latent period may be up to 48 hours following GAH exposure. CNS, central nervous system; EOM, extraocular muscle; AKI, acute kidney injury.
REFERENCES
- 1. Ko DR, Chung SP, You JS, et al. Effects of paraquat ban on herbicide poisoning-related mortality. Yonsei Med J 2017;58:859-66.
- 2. Lee JW, Hwang IW, Kim JW, et al. Common pesticides used in suicide attempts following the 2012 paraquat ban in Korea. J Korean Med Sci 2015;30:1517-21.
- 3. Dawson AH, Eddleston M, Senarathna L, et al. Acute human lethal toxicity of agricultural pesticides: a prospective cohort study. PLoS Med 2010;7:e1000357.
- 4. Kim GW, Yoon SK, Jung YS, Choi S. [Clinical toxicology]. Koonja Publishing Inc; 2006.
- 5. Gunnell D, Eddleston M, Phillips MR, Konradsen F. The global distribution of fatal pesticide self-poisoning: systematic review. BMC Public Health 2007;7:357.
- 6. Wesseling C, Corriols M, Bravo V. Acute pesticide poisoning and pesticide registration in Central America. Toxicol Appl Pharmacol 2005;207(2 Suppl):697-705.
- 7. Office of Prevention, Pesticides and Toxic Substances. Denial of registration of chlorfenapyr for use on cotton [Internet]. US Environmental Protection Agency; 2000 [cited 2023 Oct 30]. Available from: https://archive.epa.gov/opprd001/chlorfenapyr/web/pdf/chlorfenapyr.pdf
- 8. US Environmental Protection Agency (EPA). Chlorfenapyr pesticide fact sheet [Internet]. EPA; 2001 [cited 2023 Oct 30]. Available from: https://www3.epa.gov/pesticides/chem_search/reg_actions/registration/fs_PC-129093_01-Jan-01.pdf
- 9. Kwon JS, Kim HY, Han HJ, Kim JY, Park JH. A case of chlorfenapyr intoxication with central nervous system involvement. J Clinic Toxicol 2012;2:147.
- 10. Tharaknath VR, Prabhakar YV, Kumar KS, Babu NK. Clinical and radiological findings in chlorfenapyr poisoning. Ann Indian Acad Neurol 2013;16:252-4.
- 11. Baek BH, Kim SK, Yoon W, Heo TW, Lee YY, Kang HK. Chlorfenapyr-induced toxic leukoencephalopathy with radiologic reversibility: a case report and literature review. Korean J Radiol 2016;17:277-80.
- 12. Kim IS, Kim JH, Kim JB, Kim JH. Chlorfenapyr intoxication manifested by extensive leukoencephalomyelopathy. J Korean Neurol Assoc 2018;36:390-2.
- 13. Park SJ, Jung JU, Kang YK, Chun BY, Son BJ. Toxic optic neuropathy caused by chlorfenapyr poisoning. J Korean Ophthalmol Soc 2018;59:1097-102.
- 14. Kim JH, Park NH, Park JY, Kim SJ. Magnetic resonance imaging and clinical features of chlorfenapyr-induced toxic leukoencephalopathy: a case report. Taehan Yongsang Uihakhoe Chi 2020;81:985-9.
- 15. Chien SC, Chien SC, Su YJ. A fatal case of chlorfenapyr poisoning and a review of the literature. J Int Med Res 2022;50:3000605221121965.
- 16. World Health Organization (WHO). The WHO recommended classifcation of pesticides by harzard and guidelines to classification 2019. WHO; 2020.
- 17. Metruccio F, Boobis A. Chlorfenapyr. Documents: tox monograph: 2012 MONOGRAPH final [Internet]. World Health Organization; 2012 [cited 2023 Oct 30]. Available from: http://apps.who.int/pesticide-residues-jmpr-database/pesticide?name=CHLORFENAPYR
- 18. Hollingworth RM, Gadelhak GG. Mechanisms of action and toxicity of new pesticides that disrupt oxidative phosphorylation. Rev in Toxicol 1998;2:253-66.
- 19. Black BC, Hollingworth RM, Ahammadsahib KI, Kukel CD, Donovan S. Insecticidal action and mitochondrial uncoupling activity of AC-303,630 and related halogenated pyrroles. Pestic Biochem Physiol 1994;50:115-28.
- 20. Hunt DA, Treacy MF. Pyrrole insecticides: a new class of agriculturally important insecticides functioning as uncouplers of oxidative phosphorylation; In: Ishaaya I, Degheele D, editors. Insecticides with novel modes of action: mechanism and application. Springer; 1998.
- 21. Periasamy S, Deng JF, Liu MY. Who is the real killer? Chlorfenapyr or detergent micelle-chlorfenapyr complex? Xenobiotica 2017;47:833-5.
- 22. Endo Y, Tachibana S, Hirano J, et al. Acute chlorfenapyr poisoning. Chudoku Kenkyu 2004;17:89-93.
- 23. Choi UT, Kang GH, Jang YS, Ahn HC, Seo JY, Sohn YD. Fatality from acute chlorfenapyr poisoning. Clin Toxicol (Phila) 2010;48:458-9.
- 24. Ku JE, Joo YS, You JS, Chung SP, Lee HS. A case of survival after chlorfenapyr intoxication with acute pancreatitis. Clin Exp Emerg Med 2015;2:63-6.
- 25. Chomin J, Heuser W, Nogar J, Ramnarine M, Stripp R, Sud P. Delayed hyperthermia from chlorfenapyr overdose. Am J Emerg Med 2018;36:2129.
- 26. Kang C, Kim DH, Kim SC, Kim DS. A patient fatality following the ingestion of a small amount of chlorfenapyr. J Emerg Trauma Shock 2014;7:239-41.
- 27. Wu B, Xue F, Lu M, Ma A, Fan L. Experience in the treatment of chlorfenapyr poisoning. J Toxicol Sci 2023;48:221-5.
- 28. Han SK, Yeom SR, Lee SH, et al. A fatal case of chlorfenapyr poisoning following dermal exposure. Hong Kong J Emerg Med 2019;26:375-8.
- 29. Lee JY. Delayed death after chlorfenpyr poisoning. J Korean Soc Clin Toxicol 2021;19:51-4.
- 30. Luo ZH, Chen YQ, Lin JR, Jiang WZ. A case report of death from acute emamectin•chlorfenapyr poisoning. Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi 2020;38:534-5.
- 31. Zhang S, Deng Y, Gao Y. Malignant hyperthermia-like syndrome in acute chlorfenapyr poisoning: a case report. Heliyon 2022;8:e10051.
- 32. Qiu C, Sun H, Xiao H, Cao Y. Clinical and CT manifestations of delayed toxic encephalopathy caused by low-dose chlorfenapyr poisoning: a case report. J Clin Toxicol 2020;11:464.
- 33. Chung MJ, Mao YC, Hsu CT, et al. A fatal case of chlorfenapyr poisoning and the therapeutic implications of serum chlorfenapyr and tralopyril levels. Medicina (Kaunas) 2022;58:1630.
- 34. Hoshiko M, Naito S, Koga M, Mori M, Hara K, Ishitake T. Case report of acute death on the 7th day due to exposure to the vapor of the insecticide chlorfenapyr. Chudoku Kenkyu 2007;20:131-6.
- 35. Lee J, Lee JH, Baek JM, et al. Toxicity from intra-abdominal injection of chlorfenapyr. Case Rep Emerg Med 2013;2013:425179.
- 36. Qu JL, Yan HY, Zhu XC, Hao YG. Three cases of acute chlorfenapyr poisoning. Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi 2023;41:461-2.
- 37. Kanungo D, Dellarco V, Davies L. Bentazone [Internet]. World Health Organization; 2012 [cited 2023 Oct 30]. Available from: https://apps.who.int/pesticide-residues-jmpr-database/Document/52
- 38. Scalla R, Gauvrit C. [Mechanisms of phytotoxic action of other families of herbicides]; In: Scalla R, editor. [Herbicides: mode of action and principles of use]. French National Institute of Agricultural Research (INRA); 1991. p.115-91.
- 39. Turcant A, Harry P, Cailleux A, et al. Fatal acute poisoning by bentazon. J Anal Toxicol 2003;27:113-7.
- 40. Lin TJ, Hung DZ, Hu WH, Yang DY, Wu TC. Acute basagran poisoning mimicking neuroleptic malignant syndrome. Hum Exp Toxicol 1999;18:493-4.
- 41. Muller IB, Willads Petersen H, Johansen SS, Theilade P. Fatal overdose of the herbicide bentazone. Forensic Sci Int 2003;135:235-6.
- 42. Wu IW, Wu MS, Lin JL. Acute renal failure induced by bentazone: 2 case reports and a comprehensive review. J Nephrol 2008;21:256-60.
- 43. Jung HM, Kim JH, Han SB, Paik JH, Kim JY, Kim JS. A case of bentazone poisoning mimicking organophosphate intoxication. J Korean Soc Clin Toxicol 2010;8:122-4.
- 44. Lee K. A fatal case of acute bentazone overdose despite cricothyroidotomy during cardiopulmonary resuscitation. Clin Exp Emerg Med 2017;4:254-7.
- 45. Skavic P, Durakovic Z, Nestic M. Lethal bentazone intoxication: a report of two cases. J Forensic Sci 2018;63:321-5.
- 46. Talbot AR, Shiaw MH, Huang JS, et al. Acute poisoning with a glyphosate-surfactant herbicide ('Roundup'): a review of 93 cases. Hum Exp Toxicol 1991;10:1-8.
- 47. Chen YJ, Wu ML, Deng JF, Yang CC. The epidemiology of glyphosate-surfactant herbicide poisoning in Taiwan, 1986-2007: a poison center study. Clin Toxicol (Phila) 2009;47:670-7.
- 48. Bacon MH, Vandelac L, Gagnon MA, Parent L. Poisoning regulation, research, health, and the environment: the glyphosate-based herbicides case in Canada. Toxics 2023;11:121.
- 49. Tominack RL. Herbicide formulations. J Toxicol Clin Toxicol 2000;38:129-35.
- 50. Bradberry SM, Proudfoot AT, Vale JA. Glyphosate poisoning. Toxicol Rev 2004;23:159-67.
- 51. Kamijo Y, Takai M, Sakamoto T. A multicenter retrospective survey of poisoning after ingestion of herbicides containing glyphosate potassium salt or other glyphosate salts in Japan. Clin Toxicol (Phila) 2016;54:147-51.
- 52. Koyama K, Kasuya Y, Koyama K, Goto K. Nitric oxide-mediated vasorelaxation induced by sodium polyoxyethylene laurylether sulfate. Toxicol Appl Pharmacol 1997;145:294-300.
- 53. Tominack RL, Yang GY, Tsai WJ, Chung HM, Deng JF. Taiwan National Poison Center survey of glyphosate-surfactant herbicide ingestions. J Toxicol Clin Toxicol 1991;29:91-109.
- 54. Lin CM, Lai CP, Fang TC, Lin CL. Cardiogenic shock in a patient with glyphosate-surfactant poisoning. J Formos Med Assoc 1999;98:698-700.
- 55. Lee HL, Chen KW, Chi CH, Huang JJ, Tsai LM. Clinical presentations and prognostic factors of a glyphosate-surfactant herbicide intoxication: a review of 131 cases. Acad Emerg Med 2000;7:906-10.
- 56. Thakur DS, Khot R, Joshi PP, Pandharipande M, Nagpure K. Glyphosate poisoning with acute pulmonary edema. Toxicol Int 2014;21:328-30.
- 57. Jyoti W, Thabah MM, Rajagopalan S, Hamide A. Esophageal perforation and death following glyphosate poisoning. J Postgrad Med 2014;60:346-7.
- 58. Kato Y. Three cases of an extreme hyperkalemia associated with glyphosate potassium herbicide poisoning. Chudoku Kenkyu 2015;28:368-70.
- 59. Ghosh S, Tale S, Kolli M, Kaur S, Garbhapu A, Bhalla A. Cardiogenic shock with first-degree heart block in a patient with glyphosate-surfactant poisoning. Trop Doct 2021;51:244-6.
- 60. Luo W, Lu T, Li F, et al. Surgical treatment of pyloric stenosis caused by glyphosate poisoning: a case report. Medicine (Baltimore) 2019;98:e16590.
- 61. Chang ET, Odo NU, Acquavella JF. Systematic literature review of the epidemiology of glyphosate and neurological outcomes. Int Arch Occup Environ Health 2023;96:1-26.
- 62. Cho AY, Oh JH, Oh SS, Lee KY, Sun IO. Clinical characteristics of acute kidney injury in patients with glyphosate surfactant herbicide poisoning. Kidney Res Clin Pract 2023;42:349-57.
- 63. Lee JW, Choi YJ, Park S, Gil HW, Song HY, Hong SY. Serum S100 protein could predict altered consciousness in glyphosate or glufosinate poisoning patients. Clin Toxicol (Phila) 2017;55:357-9.
- 64. Wijerathna TM, Mohamed F, Gawarammana IB, et al. Cellular injury leading to oxidative stress in acute poisoning with potassium permanganate/oxalic acid, paraquat, and glyphosate surfactant herbicide. Environ Toxicol Pharmacol 2020;80:103510.
- 65. Dou JR, Zhou X, Miao RF, et al. Analysis of clinical characteristics and prognostic factors in 40 cases of acute glyphosate poisoning. Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi 2021;39:676-81.
- 66. Jovic-Stosic J, Putic V, Perkovic-Vukcevic N, Babic G, Dordevic S, Segrt Z. Intravenous lipid emulsion in treatment of cardiocirculatory disturbances caused by glyphosate-surfactant herbicide poisoning. Vojnosanit Pregl 2016;73:390-2.
- 67. Lee MJ, Min YG. Hemodynamic changes after infusion of intravenous lipid emulsion to treat refractory hypotension caused by glyphosate-surfactant herbicide poisoning: a case report. Medicine (Baltimore) 2019;98:e14156.
- 68. Gil HW, Park JS, Park SH, Hong SY. Effect of intravenous lipid emulsion in patients with acute glyphosate intoxication. Clin Toxicol (Phila) 2013;51:767-71.
- 69. Tao Y, Han J, Cui S, Jian X, Kan B. Treatment of gastrointestinal corrosive burns caused by highly lethal glyphosate solution poisoning. J Coll Physicians Surg Pak 2022;32:SS131-3.
- 70. Wang D, Zhang G, Zhang W, Luo J, Zhu L, Hu J. Successful extracorporeal membrane oxygenation support for severe acute diquat and glyphosate poisoning: a case report. Medicine (Baltimore) 2019;98:e14414.
- 71. Knezevic V, Bozic D, Budosan I, Celic D, Milosevic A, Mitic I. Early continuous dialysis in acute glyphosate-surfactant poisoning. Srp Arh Celok Lek 2012;140:648-52.
- 72. Bando H, Murao Y, Aoyagi U, Hirakawa A, Iwase M, Nakatani T. Extreme hyperkalemia in a patient with a new glyphosate potassium herbicide poisoning: report of a case. Chudoku Kenkyu 2010;23:246-9.
- 73. Hirose Y, Kobayashi M, Koyama K, et al. A toxicokinetic analysis in a patient with acute glufosinate poisoning. Hum Exp Toxicol 1999;18:305-8.
- 74. Ebert E, Leist KH, Mayer D. Summary of safety evaluation toxicity studies of glufosinate ammonium. Food Chem Toxicol 1990;28:339-49.
- 75. Hori Y, Tanaka T, Fujisawa M, Shimada K. Toxicokinetics of DL-glufosinate enantiomer in human BASTA poisoning. Biol Pharm Bull 2003;26:540-3.
- 76. Matsumura N, Takeuchi C, Hishikawa K, Fujii T, Nakaki T. Glufosinate ammonium induces convulsion through N-methyl-D-aspartate receptors in mice. Neurosci Lett 2001;304:123-5.
- 77. Koyama K. Glufosinate and a surfactant: which component produces effects on the central nervous system in acute oral BASTA poisoning? Vet Hum Toxicol 1999;41:341.
- 78. Lluis M, Nogue S, Miro O. Severe acute poisoning due to a glufosinate containing preparation without mitochondrial involvement. Hum Exp Toxicol 2008;27:519-24.
- 79. Yeon S, Kim SH, Sim J, et al. Major component causing neurological toxicity in acute glufosinate ammonium poisoning: determination of glufosinate, 1-methoxy-2-propanol, and ammonia in serum and cerebrospinal fluid. Clin Toxicol (Phila) 2022;60:286-92.
- 80. Koyama K, Koyama K, Goto K. Cardiovascular effects of a herbicide containing glufosinate and a surfactant: in vitro and in vivo analyses in rats. Toxicol Appl Pharmacol 1997;145:409-14.
- 81. Lawson R, Estrade-Chapellaz E. Self-induced poisoning with glufosinate (Basta). Ann Fr Anesth Reanim 1999;18:1025-6.
- 82. Watanabe T, Sano T. Neurological effects of glufosinate poisoning with a brief review. Hum Exp Toxicol 1998;17:35-9.
- 83. Takahashi H, Toya T, Matsumiya N, Koyama K. A case of transient diabetes insipidus associated with poisoning by a herbicide containing glufosinate. J Toxicol Clin Toxicol 2000;38:153-6.
- 84. Paik JH, Kim JS, Yi HG, Park HJ, Ha CK, Roh HK. A case of acute glufosinate ammonium (BASTA) intoxication associated with various neurological abnormalities. J Korean Soc Clin Toxicol 2005;3:103-6.
- 85. Mao YC, Hung DZ, Wu ML, et al. Acute human glufosinate-containing herbicide poisoning. Clin Toxicol (Phila) 2012;50:396-402.
- 86. Inoue Y, Onodera M, Fujita Y, Fujino Y, Kikuchi S, Endo S. Factors associated with severe effects following acute glufosinate poisoning. Clin Toxicol (Phila) 2013;51:846-9.
- 87. Choi J, Lee SJ, Jung I, et al. Ictal eletroencephalographic findings of nonconvulsive status epilepticus associated with glufosinate ammonium poisoning. J Korean Neurol Assoc 2017;35:117-9.
- 88. Kim J, Cho YS, Chun BJ, et al. The trend of ammonia levels in patients with glufosinate ammonium poisoning with respect to neurotoxicity. Naunyn Schmiedebergs Arch Pharmacol 2023;396:525-31.
- 89. Oh HJ, Choi HC, Shon JH, Jang MU, Kim C. Bilateral basal ganglia lesion after glufosinate ammonium (BASTA) intoxication. J Neurocrit Care 2014;7:125-8.
- 90. Jeong TO, Yoon JC, Lee JB, Jin YH, Hwang SB. Reversible splenial lesion syndrome (RESLES) following glufosinate ammonium poisoning. J Neuroimaging 2015;25:1050-2.
- 91. Kim YK, Kim KH, Moon HJ, et al. Predicting acute intoxication of glufosinate-containing herbicides: a comparative study of a group with complication versus the others without complication in single institution. J Korean Soc Emerg Med 2016;27:52-60.
- 92. Lee HJ, Kang JH. Prolonged cognitive dysfunction in patient with splenial lesion of the corpus callosum caused by glufosinate ammonium poisoning. Turk J Emerg Med 2021;21:82-5.
- 93. Zhang XM, Sun H, Zhang JS, Hu DL, Zhang Q. A case of glufosinate-ammonium poisoning in a patient with total gastrectomy. Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi 2021;39:366-7.
- 94. Kim HY, Park NH. Diffusion-weighted imaging for detecting glufosinate ammonium intoxication: a case report. J Korean Soc Radiol 2022;83:1354-9.
- 95. Tanaka J, Yamashita M, Yamamoto T. A comparative study of direct hemoperfusion and hemodialysis for the removal of glufosinate ammonium. J Toxicol Clin Toxicol 1995;33:691-4.
- 96. Tanaka J, Yamashita M, Yamashita M, Matsuo H, Yamamoto T. Two cases of glufosinate poisoning with late onset convulsions. Vet Hum Toxicol 1998;40:219-22.
- 97. Mao YC, Wang JD, Hung DZ, Deng JF, Yang CC. Hyperammonemia following glufosinate-containing herbicide poisoning: a potential marker of severe neurotoxicity. Clin Toxicol (Phila) 2011;49:48-52.
- 98. Lee DK, Youk H, Kim H, et al. Initial serum ammonia as a predictor of neurologic complications in patients with acute glufosinate poisoning. Yonsei Med J 2016;57:254-9.
- 99. Cha YS, Kim H, Lee Y, et al. The relationship between serum ammonia level and neurologic complications in patients with acute glufosinate ammonium poisoning: a prospective observational study. Hum Exp Toxicol 2018;37:571-9.
- 100. Kyong YY, Choi KH, Oh YM, Lee KU. "Hyperammonemia following glufosinate-containing herbicide poisoning: a potential marker of severe neurotoxicity" by Yan-Chido Mao et al., Clin Toxicol (Phila) 2011; 49:48-52. Clin Toxicol (Phila) 2011;49:510-2.
- 101. Lee J, Lee Y, Kim YS, et al. Serum ammonia as an early predictor of in-hospital mortality in patients with glufosinate poisoning. Hum Exp Toxicol 2019;38:1007-13.
- 102. Gil HW, Jeong MH, Park JS, Choi HW, Kim SY, Hong SY. An outbreak of food borne illness due to methomyl pesticide intoxication in Korea. J Korean Med Sci 2013;28:1677-81.
- 103. Bardin PG, van Eeden SF, Moolman JA, Foden AP, Joubert JR. Organophosphate and carbamate poisoning. Arch Intern Med 1994;154:1433-41.
- 104. Saadeh AM, Farsakh NA, al-Ali MK. Cardiac manifestations of acute carbamate and organophosphate poisoning. Heart 1997;77:461-4.
- 105. Jokanovic M. Medical treatment of acute poisoning with organophosphorus and carbamate pesticides. Toxicol Lett 2009;190:107-15.
- 106. Burgess JL, Bernstein JN, Hurlbut K. Aldicarb poisoning: a case report with prolonged cholinesterase inhibition and improvement after pralidoxime therapy. Arch Intern Med 1994;154:221-4.
- 107. Gil HW, Hong JR, Song HY, Hong SY. A case of methanol intoxication caused by methomyl pesticide ingestion. Hum Exp Toxicol 2012;31:1299-302.
- 108. Jang TC, Jang JH, Lee KW. Mechanism of acute endosulfan intoxication-induced neurotoxicity in Sprague-Dawley rats. Arh Hig Rada Toksikol 2016;67:9-17.
- 109. Moses V, Peter JV. Acute intentional toxicity: endosulfan and other organochlorines. Clin Toxicol (Phila) 2010;48:539-44.
- 110. Moon JM, Chun BJ. Acute endosulfan poisoning: a retrospective study. Hum Exp Toxicol 2009;28:309-16.
- 111. Blanco-Coronado JL, Repetto M, Ginestal RJ, Vicente JR, Yelamos F, Lardelli A. Acute intoxication by endosulfan. J Toxicol Clin Toxicol 1992;30:575-83.
- 112. Eyer F, Felgenhauer N, Jetzinger E, Pfab R, Zilker TR. Acute endosulfan poisoning with cerebral edema and cardiac failure. J Toxicol Clin Toxicol 2004;42:927-32.
- 113. Durukan P, Ozdemir C, Coskun R, et al. Experiences with endosulfan mass poisoning in rural areas. Eur J Emerg Med 2009;16:53-6.
- 114. Kim SE, Kim SI, Lee JB, et al. Clinical analysis of acute endosulfan poisoning: single center experience. J Korean Soc Clin Toxicol 2015;13:71-7.
- 115. Moon JM, Chun BJ, Lee SD. In-hospital outcomes and delayed neurologic sequelae of seizure-related endosulfan poisoning. Seizure 2017;51:43-9.
- 116. Park HR, Song P, Lee JJ, Cho JY. Endosulfan-induced prolonged super-refractory status epilepticus. J Epilepsy Res 2018;8:93-6.
