Glyphosate and Polyoxyethyleneamine Ingestion Leading to Renal, Hepatic, and Pulmonary Failure.

ABSTRACT: Glyphosate is an organophosphorus compound and the active ingredient in commonly used herbicides, whereas polyoxyethyleneamine (POEA) is a nonionic surfactant often coupled with glyphosate in these herbicides to increase their efficacy. Cases of glyphosate-POEA ingestion have shown a variety of outcomes, ranging from skin and mucosal surface irritation to death. Here, we report mortality after ingestion of at least 237 mL of an herbicide confirmed to contain both glyphosate and POEA. The decedent's electronic medical record indicates presentation to the emergency department shortly after ingestion and rapid decompensation, with death occurring on the fourth day of admission. The autopsy report showed extensive pulmonary edema and congestion with no alimentary tract abnormalities. Microscopically, airway inflammation, edema, and hemorrhage were shown as well as pericentral necrosis and macrovascular hepatic steatosis. This case is unusual for several reasons including the fatal outcome in a young 30-year-old patient, the large volume of the herbicide consumed, the associated large volume aspirated, and the lung pathology associated with exposure to glyphosate-POEA since inhalation, and in this case, aspiration is an uncommon route of glyphosate-POEA exposure. This report therefore offers rare respiratory tract pathological findings and the clinical course after aspiration of a large volume of glyphosate-POEA.

Cardiogenic shock with first-degree heart block in a patient with glyphosate-surfactant poisoning.

Glyphosate is a commonly used non-selective herbicide in agriculture and aquafarms. Gastrointestinal, respiratory and cardiovascular symptoms are predominant manifestations of glyphosate poisoning. Cardiac dysfunction should be kept as a possibility in patients presenting with shock, and the treatment is mainly supportive. We present such a case.

Acute chemical ingestion in the under 19 population in South Korea: A brief report.

BACKGROUND: Most people are frequently exposed to chemicals and chemical products. This study provides basic information on the outcomes of acute chemical ingestion of patients aged under 19 years. METHODS: Patients aged under 19 years who had ingested chemicals and thus visited the emergency department between January 2011 and December 2016 were included in this study. RESULTS: In all, 1,247 patients included (1,145 in the unintentional group and 102 in the intentional group). The mean age was 3.27±4.77 in the unintentional ingestion group and 16.49±1.94 in the intentional group. In the unintentional group, detergents were most frequently ingested (by 219 patients), followed by hypochlorite-based agents, ethanol, sodium hydroxide, acetone, silica gel, and citric acid. Cases of boric acid (odds ratio [OR] = 6.131), ethylene glycol (OR = 6.541), glacial acetic acid (OR = 7.644), other hydrocarbons (OR = 4.496), hypochlorite-based agent (OR = 2.627), nicotine (OR = 5.635), and sodium peroxocarbonate (OR = 6.783) ingestion was associated with a significantly high admission rate. In the intentional group, there were 54 cases of ingestion of hypochlorite-based agent, followed by detergent, ethylene glycol, ethanol, methanol and sodium peroxycarbonate. The significant risk factors for admission in the intentional group were ingestion of ethylene glycol (OR = 37.333) and hypochlorite-based agent (OR = 5.026). There was no mortality case. CONCLUSION: The most commonly ingested substances were sodium hypochlorite (hypochlorite-related agent), surfactants (detergent and soap), and ethanol. The ingestion of hypochlorite or ethylene glycol was the main risk factor for admission. Intentional ingestion was higher in adolescents than in children.

Cellular injury leading to oxidative stress in acute poisoning with potassium permanganate/oxalic acid, paraquat, and glyphosate surfactant herbicide.

Previous studies on human acute kidney injury (AKI) following poisoning with potassium permanganate/oxalic acid (KMnO4/H2C2O4), paraquat, and glyphosate surfactant herbicide (GPSH) have shown rapid and large increases in serum creatinine (sCr) that cannot be entirely explained by direct nephrotoxicity. One plausible mechanism for a rapid increase in sCr is oxidative stress. Thus, we aimed to explore biomarkers of oxidative stress, cellular injury, and their relationship with sCr, after acute KMnO4/H2C2O4, paraquat, and GPSH poisonings. Serum biomarkers [sCr, creatine (sCn), cystatin C (sCysC)] and urinary biomarkers [cytochrome C (CytoC), 8-isoprostane (8-IsoPs)] were evaluated in 105 patients [H2C2O4/KMnO4 (N = 57), paraquat, (N = 21), GPSH (N = 27)] recruited to a multicenter cohort study. We used area under the receiver operating characteristics curve (AUC-ROC) to quantify the extent of prediction of moderate to severe AKI (acute kidney injury network stage 2/3 (AKIN2/3)). Patients with AKIN2/3 showed increased levels of CytoC. Early high CytoC predicted AKIN2/3 in poisoning with KMnO4/H2C2O4 (AUC-ROC4-8h: 0.81), paraquat (AUC-ROC4-8h: 1.00), and GPSH (AUC-ROC4-8h: 0.91). 8-Isoprostane levels were not significantly elevated. Reduced sCn and increased sCr/sCn ratios were observed for 48 h post KMnO4/H2C2O4 ingestion. Paraquat exhibited a similar pattern (N = 11), however only 3 were included in our study. Increased CytoC suggests there is mitochondrial injury coupled with energy depletion. The increased sCr within 24 h could be due to increased conversion of cellular creatine to creatinine during the process of adenosine triphosphate (ATP) generation and then efflux from cells. Later increases of sCr are more likely to represent a true decrease in kidney function.

Increased severity associated with tallowamine in acute glyphosate poisoning.

Context: During the re-approval process of glyphosate in Europe, it was mentioned that glyphosate-based products (GBF) were more toxic than glyphosate alone. This phenomenon was attributed to the surfactants and among them, polyethoxylated tallowamine (POEA) has been suspected to significantly contribute to the toxicity of glyphosate products. In animal data acute oral toxicity of POEA has been suggested to be greater than glyphosate toxicity in animal studies. There are no data, however, comparing the clinical signs and severity of acute human poisoning with tallowamine-containing GBF (TA) and non-tallowamine-containing GBF (NTA). The aim of this study was to compare the severity of oral poisoning between TA and NTA cases, reported to the French Poison Control Centres (PCC) over 7 years.Methods: This is a retrospective study of cases of oral exposure to GBF reported to French PCCs between January 1st, 2008 and December 12th, 2014. The formulation of every GBF was reviewed using the PCC national database of products and compositions, to identify cases involving TA, NTA, or GBF with unknown co-formulants.Results: Between 2008 and 2014, 1362 cases of GBF ingestion were registered in the PCC national database of poisoning cases. Among them, 429 were symptomatic acute cases of ingestion of GBF. There were 235 exposures to TA, 105 to NTA, and 89 to unknown GBF. There were more severe cases in the TA group than in the NTA group (p = 0.037).Discussion: The present study shows that POEA rather than other co-formulants leads to more severe symptoms in those patients ingesting GBF. The acute toxicity of POEA might be explained by its irritating properties; in experimental studies, it caused skin irritation and severe eye and mucous membranes irritation.Conclusion: In this study, severe respiratory symptoms were also more frequently reported in the TA group. The surfactant properties of POEA are likely to cause aspiration pneumonitis which is a plausible explanation for the respiratory failure complicating severe GBF poisoning cases.

Hemodynamic changes after infusion of intravenous lipid emulsion to treat refractory hypotension caused by glyphosate-surfactant herbicide poisoning: A case report.

RATIONALE: Glyphosate-surfactant herbicides (GlySH) are non-selective herbicides that are extensively used worldwide. A recent case report on GlySH poisoning suggested successful resuscitation upon using intravenous lipid emulsion (ILE) for refractory hypotension. The efficacy of ILE in GlySH poisoning remains unproven due to a lack of randomized controlled trials, and further evidence is required to clarify the mechanism by which ILE may reverse hypotension in GlySH poisoning. PATIENT CONCERNS: A 46-year-old man presented to the emergency department 45 min following ingestion of approximately 200 cc of GlySH. On arrival, his vital signs were as follows: blood pressure, 82/50 mmHg and pulse, 85 beats/min. Hypotension did not respond to fluid resuscitation and norepinephrine infusion; his cardiac output (CO) was 4.5 L/min and systemic vascular resistance (SVR) was 604 dynes·s·cm with blood pressure of 63/35 mmHg. DIAGNOSIS: GlySH poisoning presented with refractory hypotension. INTERVENTIONS: A bolus (100 mL) of ILE was infused with subsequent infusion of 400 mL over 4 h. OUTCOMES: A few minutes following the bolus of ILE, his blood pressure increased to 101/54 mmHg with CO of 6.5 L/min and SVR of 701 dynes·s·cm. Blood pressure, CO, and stroke volume increased gradually over next 8.5 h. His clinical status improved gradually, and norepinephrine could be tapered on hospital day (HD) 3. The patient was discharged at HD 10 without sequelae. LESSONS: ILE could be used as a rescue treatment in case of a poor response to conventional fluid and vasopressor therapy. The underlying mechanism of rescue with ILE might be a positive inotropic effect.

Toxicity of soluble film automatic dishwashing products as reported to the United Kingdom National Poisons Information Service 2008-2015.

INTRODUCTION: Soluble film automatic dishwashing tablets, unlike their traditional counterparts, require no removal from an outer protective wrapper prior to use. Instead, the tablets are enclosed by a water-soluble polyvinyl alcohol film and are loaded straight into the dishwashing machine. They most commonly contain a source of hydrogen peroxide (often as sodium percarbonate) and non-ionic surfactants. Other constituents in some formulations include sodium carbonate, sodium tripolyphosphate and sodium silicate, which reduce water hardness. The pH once dissolved in water is alkaline. OBJECTIVE: To determine the toxicity from exposure to soluble film automatic dishwashing tablets. METHODS: Telephone enquiries to the United Kingdom National Poisons Information Service regarding soluble film automatic dishwashing products were analysed retrospectively for the period January 2008 to December 2015. RESULTS: There were 498 enquiries relating to 488 patients. Almost all exposures occurred in the home (98.4%) and involved children aged ≤5 years (92.8%). Exposure occurred mainly as a result of ingestion alone (n = 470, 96.3%); eye contact alone (n = 9, 1.8%) and exposures involving multiple routes (ingestion with skin or eye contact; n = 9, 1.8%) made up the remaining cases. The majority of patients were asymptomatic following exposure (n = 325, 67.4%). The most common feature following ingestion was vomiting which occurred in 121 of 474 cases (25.5%) where clinical data were available. Nausea (n = 8, 1.7%) and coughing (n = 6, 1.3%) were also reported; three patients developed stomatitis and another five developed a rash where ingestion alone was considered to be the sole route of exposure. Ocular exposure to the tablet contents resulted in blurred vision, eye pain or conjunctivitis in seven of ten patients. CONCLUSION: Ingestion of a soluble film automatic dishwashing tablet rarely resulted in clinically significant symptoms, which is surprising given the potential hazard of the ingredients. Hence, it seems probable that the amount of material actually ingested was very small or that most was spat out.

Pharmacological treatment of organophosphorus insecticide poisoning: the old and the (possible) new.

Despite being a major clinical and public health problem across the developing world, responsible for at least 5 million deaths over the last three decades, the clinical care of patients with organophosphorus (OP) insecticide poisoning has little improved over the last six decades. We are still using the same two antidotes - atropine and oximes - that first came into clinical use in the late 1950s. Clinical research in South Asia has shown how improved regimens of atropine can prevent deaths. However, we are still unsure about which patients are most likely to benefit from the use of oximes. Supplemental antidotes, such as magnesium, clonidine and sodium bicarbonate, have all been proposed and studied in small trials without production of definitive answers. Novel antidotes such as nicotinic receptor antagonists, beta-adrenergic agonists and lipid emulsions are being studied in large animal models and in pilot clinical trials. Hopefully, one or more of these affordable and already licensed antidotes will find their place in routine clinical care. However, the large number of chemically diverse OP insecticides, the varied poisoning they produce and their varied response to treatment might ultimately make it difficult to determine definitively whether these antidotes are truly effective. In addition, the toxicity of the varied solvents and surfactants formulated with the OP active ingredients complicates both treatment and studies. It is possible that the only effective way to reduce deaths from OP insecticide poisoning will be a steady reduction in their agricultural use worldwide.

A multicenter retrospective survey of poisoning after ingestion of herbicides containing glyphosate potassium salt or other glyphosate salts in Japan.

INTRODUCTION: A multicenter retrospective survey of patients poisoned by herbicides containing glyphosate salts in Japan was conducted to identify differences in symptoms and outcome of poisoning. METHODS: Participants were patients who were transported to emergency facilities between October 2006 and March 2014 after consuming herbicides containing glyphosate potassium salt (GlyK(+)) (the K-group) or other glyphosate salts (the O-group). Questionnaires were mailed to 38 emergency facilities that agreed to participate in the study. RESULTS: Serum potassium levels upon arrival were significantly higher (p < 0.01), and abnormal electrocardiogram findings were significantly more common (p < 0.01) in the K-group (n = 55) than in the O-group (n = 62). Conversely, acute lung injury (ALI) including acute respiratory distress syndrome (ARDS) (p = 0.05) and liver injury (LI) (p < 0.01) were significantly more common during hospitalization in the O-group, although no significant differences in the duration of hospital stay (p = 0.92) or outcomes (p = 0.95) were observed between the two groups. DISCUSSION AND CONCLUSION: The ingestion of products containing glyphosate isopropylamine or ammonium salts, and polyoxyethyleneamine (POEA) as a surfactant, can cause severe organ injury. Physicians should note that the ingestion of products containing glyphosate potassium salt and surfactants other than POEA can cause hyperkalemia, potentially leading to fatal arrhythmias or cardiac arrest.

An autopsy case of fatal repellent air freshener poisoning.

We describe a first fatal case of repellent air freshener ingestion. A 79-year-old Japanese man with Alzheimer-type senile dementia orally ingested repellent air freshener containing three surfactants: polyoxyethylene 9-lauryl ether, polyoxyethylene (40) hydrogenated castor oil, and lauric acid amidopropyl amine oxide (weight ratio of 1.3%). About 1h after the collapse, he was in cardiopulmonary arrest and subsequently died 10h after his arrival. The forensic autopsy performed 5.5h after death revealed the 380ml of stomach contents with a strong mint perfume identical to that of the repellent air freshener and the findings of acute death. Toxicologically, 9.1µg/ml and 558.2µg/ml of polyoxyethylene 9-lauryl ether were detected from the serum and stomach contents taken at autopsy. Generally, ingestion of anionic or non-ionic surfactants have been considered as safe. However, because the patient suffered from cardiac insufficiency with a low dose of repellent air freshener ingestion, medical staff members must evaluate the elderly patient for cardiac and circulatory problems regardless of the ingested dose. Not only medical and nursing staff members, but also families who are obliged to care for elderly persons must be vigilant to prevent accidental ingestion of toxic substances generally used in the household.

Heart rate-corrected QT interval predicts mortality in glyphosate-surfactant herbicide-poisoned patients.

BACKGROUND: Glyphosate-surfactant herbicide is promoted by the manufacturer as having no risks to human health. Glyphosate surfactant has recently been used with increasing frequency in suicide attempts, so clinical toxicologists occasionally encounter cases of severe systemic toxicity. The purpose of this study was to identify the early predictive factors of patients at risk for mortality and the usefulness of the corrected QT interval (QTc interval) for predicting mortality from glyphosate-surfactant intoxication. METHODS: This was a retrospective cohort study conducted from January 2005 to December 2012. A total of 153 patients with acute glyphosate-surfactant ingestion were included. To identify the predictive factors for mortality, objective variables easily assessed at presentation including previously reported predictive factors for mortality and severity were retrospectively analyzed for their association with mortality using univariate and multiple logistic analyses. RESULTS: The average age of the patients was 56 years (range, 19-93 years). Of the 153 patients, 19 (12.4%) died. The most common abnormal electrocardiogram findings were prolonged QTc interval followed by intraventricular conduction delay and first-degree atrioventricular block. Nonsurvivors had a significantly more prolonged QTc interval when compared with that of survivors (survivors: 453.4 ± 33.6 milliseconds vs nonsurvivors: 542 ± 32.0 milliseconds, P < .001). Corrected QT interval and age were associated with a significantly increased risk of death in a multiple logistic regression. In a receiver operating curve analysis, the QTc interval had significant discriminatory power. CONCLUSION: Prolonged QTc interval seems to be a useful prognostic factor for mortality in patients intoxicated with glyphosate-surfactant herbicide.

Glufosinate herbicide intoxication causing unconsciousness, convulsion, and 6th cranial nerve palsy.

Although glufosinate ammonium herbicides are considered safe when used properly, ingestion of the undiluted form can cause grave outcomes. Recently, we treated a 34-yr-old man who ingested glufosinate ammonium herbicide. In the course of treatment, the patient developed apnea, mental deterioration, and sixth cranial nerve palsy; he has since been discharged with full recovery after intensive care. This case report describes the clinical features of glufosinate intoxication with a focus on sixth cranial nerve palsy. Our observation suggests that neurologic manifestations after ingestion of a "low-grade toxicity herbicide" are variable and more complex than that was previously considered.

Tetramethylammonium hydroxide poisoning during a pallet cleaning demonstration.

OBJECTIVES: The purpose of this study was to examine the cause of an accidental death from acute poisoning resulting from exposure to a cleaner containing tetramethylammonium hydroxide (TMAH) and to consider measures to prevent future cases. METHODS: The authors examined the details and the reason for the accidental death from acute poisoning based on the autopsy report. RESULTS: The victim was a 39-year-old male researcher with 7 years of work experience employed by a surfactant production company. The accident occurred when he was conducting a field test of a newly developed cleaner, containing 8.75% TMAH solution. The researcher spilled the cleaner on his work clothes in the area of both the hands/arms and legs. He was unconscious when discovered. An autopsy found no damage or injury that could have resulted in death other than burns to 12% of his body, and the cause of death was found to be acute poisoning by TMAH. DISCUSSION: TMAH is widely used in the electronics industry as a developer or cleaner. It is a dangerous material, causing neurotoxicity leading to respiratory failure by ganglion block that occurs through skin absorption, and no antidote has been developed yet. For this reason, it is best to completely prevent exposure by wearing proper personal protective equipment. Despite this fatal toxicity of TMAH, it is not classified in Korea as a "chemical requiring legal control". For this reason, it is urgent to raise awareness of the toxic properties of TMAH to prevent additional cases of TMAH poisoning

Glufosinate Herbicide Intoxication Causing Unconsciousness, Convulsion, and 6th Cranial Nerve Palsy

Although glufosinate ammonium herbicides are considered safe when used properly, ingestion of the undiluted form can cause grave outcomes. Recently, we treated a 34-yr-old man who ingested glufosinate ammonium herbicide. In the course of treatment, the patient developed apnea, mental deterioration, and sixth cranial nerve palsy; he has since been discharged with full recovery after intensive care. This case report describes the clinical features of glufosinate intoxication with a focus on sixth cranial nerve palsy. Our observation suggests that neurologic manifestations after ingestion of a "low-grade toxicity herbicide" are variable and more complex than that was previously considered.

Effect of intravenous fat emulsion therapy on glyphosate-surfactant-induced cardiovascular collapse.

Intravenous fat emulsion (IFE) therapy is an adjunct therapy administered to hemodynamically compromised patients with glyphosate-surfactant intoxication when they respond poorly to conventional therapies such as fluid resuscitation or vasopressors [1,2]. However, the use of IFE as an adjunct therapy in collapsed patients with glyphosate intoxication has not been reported previously. Here, we describe the case of a patient with glyphosate-surfactant­induced cardiovascular collapse who responded to IFE.