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.

Severe hypernatremia and transient azotemia in a cat following inadvertent intravenous administration of a commercial polyethylene glycol solution.

OBJECTIVE: To describe the clinical signs, clinicopathologic abnormalities, treatment, and outcome after IV administration of polyethylene glycol 3350 (PEG3350) in a cat. CASE SUMMARY: A cat was inadvertently administered 6 g/kg of PEG3350 in electrolyte solution, IV, resulting in severe hypernatremia (203 mmol/L), diffuse encephalopathy, hemolysis, and moderate azotemia. The hemolysis and acute kidney injury observed immediately following PEG3350 administration resolved with supportive care. Administration of IV and oral electrolyte-free water slowly corrected the hypernatremia and the neurologic signs subsequently improved. Complete resolution of clinical signs was documented one month following hospital discharge. The PEG3350 concentrations in serum, plasma, and urine samples confirmed toxic exposure to PEG3350. Efficacy of treatment was evident by decreasing concentrations of PEG3350 in serum after the first 24 hours of treatment. Renal elimination of PEG3350 was significant and PEG3350 was still detected in the urine 17 days after exposure. NEW INFORMATION PROVIDED: This is the first report to describe the clinical signs and clinicopathologic abnormalities in a cat intoxicated with IV PEG3350. Potential pathophysiologic mechanisms are discussed, and the successful supportive medical treatment is outlined.

Human cholestatic hepatitis owing to polyoxyethylene nonylphenol ingestion: A case report.

RATIONALE: The purpose of this study was to identify the chemical responsible for cholestatic hepatitis in a 55-year-old woman who ingested 1,1'-iminodi (octamethylene) diguanidinium triacetate (iminoctadine triacetate), a fungicide. The fungicide formulation was also composed of polyoxyethylene nonylphenol (NP-40) and methanol. PATIENT CONCERNS: Severe cholestatic hepatitis developed, which led to the patient's death on day 88 of hospitalization. Post-mortem necropsy of the liver showed focal hepatocyte necrosis involving mostly the mid-zone, along with intracytoplasmic and intracanalicular cholestasis. DIAGNOSES: To identify the chemical responsible for hepatic injury, the cellular toxicity of all chemicals in the fungicide formulation was assessed in HepG2 cells using the 3-(4,5-dimethylthiaxol-2yl)-2, 5-diphenyl tetrazolium bromide test. OUTCOMES: Viability of cells treated with the surfactant NP-40 was significantly lower (P < .001), but that of cells treated with other components of the fungicide, including the active ingredient, iminoctadine triacetate, was unaffected. Fluorescence-activated cell sorting analysis confirmed that necrosis was induced in HepG2 cells treated with 25-80 µM of NP-40, while significant numbers of apoptotic cells were not detected. LESSONS: NP-40 appears to be the chemical responsible for the patient's irreversible hepatic injury, accompanied by intracytoplasmic and intracanalicular cholestasis.

Poisoning by Polyethylene Glycol , An Adjuvant for Insecticides.

BACKGROUND: Accidental poisoning in children with surfactant used as an agriculture adjuvant is uncommon. CASE CHARACTERISTICS: A 7-month-old girl presented with severe respiratory distress 48 hours following ingestion of surfactant, and required intubation and mechanical ventilation. OUTCOME: The child was successfully managed with supportive therapy. MESSAGE: Poisoning by polyethylene glycol can be severe and life-threatening.

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.

Intravenous lipid emulsion in treatment of cardiocirculatory disturbances caused by glyphosate-surfactant herbicide poisoning.

Introduction: Glyphosate is the first widely used herbicide against weed in genetically modified crops. Though glyphosate itself has a low toxicity, commercial products are more dangerous because of increased toxicity due to surfactants addition. There is no specific antidote for the poisoning with glyphosate-surfactant (Gly-SH). In recent times, the efficacy of intravenous lipid emulsion (ILE) administration for the treatment of acute poisoning caused by Gly- SH has been investigated. Case Report: A 50-year-old man was admitted 3 hours after self-poisoning with herbicide containing glyphosate and polyoxyethyleneamine, as a surfactant. On admission, the patient was in a coma, hypotensive (80/50 mmHg) and without spontaneous breathing. Electrocardiogram showed widecomplex tachycardia, and arterial blood gas (ABG) revealed acidosis (pH 7.07). Conventional treatment included mechanical ventilation, intravenous fluids, bicarbonate and dopamine. As there was no improvement, ILE was started. The patient received 100 mL of 20% Intralipid® bolus followed by infusion of 400 mL over 20 minutes. Prior to expiration of infusion, a gradual rise in blood pressure was noted, and within 2 hours sinus rhythm was restored. Conclusion: This case report suggests that the use of ILE may be an additional option for the treatment of cardiocirculatory disturbances caused by commercial products of glyphosate herbicide.

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.

Life-threatening methemoglobinemia after unintentional ingestion of antifreeze admixtures containing sodium nitrite in the construction sites.

CONTEXT: Construction workers are exposed to a wide variety of health hazards such as poisoning at the construction sites. Various forms of poisoning incidents in construction workers have been reported. However, studies on methemoglobinemia caused by unintentional ingestion of antifreeze admixtures containing sodium nitrite at the construction sites have not been reported yet. OBJECTIVE: The aim of this study was to evaluate life-threatening methemoglobinemia after unintentional ingestion of antifreeze admixtures containing sodium nitrite at the construction sites and describe similar incidents involving ingestion of antifreeze admixtures in Korea. MATERIALS AND METHODS: Retrospective observational case series study on patients with methemoglobinemia after unintentional ingestion of antifreeze admixtures containing sodium nitrite admitted to the emergency department (ED) from January 1, 2010 to December 31, 2012 and cases reported to the Korea Occupational Safety and Health Agency (KOSHA) was performed. Results. Six victims were admitted to our ED. They had methemoglobin levels ranging from 32.4% to 71.5% and all of them recovered after receiving one (2 mg/kg) or two doses infusion of methylene blue. From the data of the KOSHA, six incidents that caused 27 victims were identified. Of 27 victims, five were included in the ED cases. For all incidents, antifreeze admixtures were not contained in their original containers and all new containers did not have a new label. All workers mistook antifreeze admixtures for water. Among the 28 victims included in this study, four died. CONCLUSION: Unintentional ingestion of antifreeze admixtures containing sodium nitrite at the construction sites can cause life-threatening methemoglobinemia. There is a need to store and label potentially hazardous materials properly to avoid unintentional ingestion at the construction sites.

Severe poisoning after accidental pediatric ingestion of glycol ethers.

Human glycol ether poisonings are sparsely reported in the medical literature. We describe a healthy 22-month-old boy who accidentally drank up to 330 mL of brake fluid containing a 75% bleed of various glycol ethers (5%-50% polyethylene glycol monomethyl ether, 15%-40% triethylene glycol monoethyl ether, 1%-30% triethylene glycol monomethyl ether, 1%-25% triethylene glycol monobutyl ether, 1%-20% polyethylene glycol, monobutyl ether, 1%-20% triethylene glycol, and <10% of other glycol ethers). Within 4 hours, he became somnolent and developed a persistent metabolic acidosis. Thirty minutes later, he received 1 dose of fomepizole. Neither progression nor improvement in clinical or metabolic status was noted after the fomepizole. He received hemodialysis for 3 hours ∼8 hours after ingestion, and his symptoms resolved resulting in an uneventfully recovery.

Aseptic meningitis in association with glyphosate-surfactant herbicide poisoning.

INTRODUCTION: The mechanisms underlying early central nervous system (CNS) signs and symptoms of glyphosate-surfactant herbicide (GlySH) poisoning are unclear. CASE PRESENTATION: A 58-year-old woman ingested approximately 150 mL of GlySH containing 41% glyphosate and 15% polyoxyethyleneamine. Two days later, she was admitted in the Emergency Center in a semicomatose state. Acute respiratory distress syndrome, circulatory collapse, acute renal failure, and disseminated intravascular coagulopathy were diagnosed. Meningitis was also suspected as she demonstrated Kernig's sign and significant neck stiffness with rigidity of the extremities as well as consciousness disturbance and fever (38.4°C). Investigations of cerebrospinal fluid (CSF) revealed the presence of glyphosate (122.5 µg/mL), significant elevation of IL-6 (394 µg/mL), and pleocytosis (32 cells/µL) with monocyte dominance. All bacteriological and virological tests were later found to be negative. She recovered completely after responding to aggressive supportive care in the intensive care unit. All signs and symptoms suggesting meningitis resolved as the concentration of glyphosate in CSF decreased. She was discharged on day 39 of hospitalization. DISCUSSION: These findings suggest that the present case involved aseptic meningitis in association with GlySH poisoning. CONCLUSION: CNS signs and symptoms induced by aseptic meningitis should be considered in cases of glyphosate-surfactant herbicide poisoning.

[Case of death occurred after an injection of aetoxisclerol. The responsibility of the product should be discussed]. / L'aetoxisclerol accusé à tort d'entraîner une mort subite.

A 35-year-old woman has suffered from faintness with cardiovascular failure at the end of a sclerotherapy session for varix management. The injected product was Aeloxisclerol (DCI lauromacrogal 400). The death came up very quickly. The autopsy didn't reveal any traumatic lesion. The anaphylactic choc could be ruled out. Macroscopically, the heart showed a right ventricular dilatation. The toxicological analysis didn't reveal any medicinal substances. Histology showed the presence of lipid degeneration of all the right-ventricle wall The discussion is carried out on the role played by this previous health-state on the onset of death, and also on the incidence of sclerotherapy using this product. and the onset of death. We are carrying out this discussion by taking in mind the nature of the product injected and the information available in the literature concerning the lipid degeneration of cardiac muscle. Quickly after this case, the AFSSAPS (The French Agency for Sanitary Security of Health Products) has emitted an written alert which correlates with the requirements of principles of precaution although it is not founded on the totality of investigation results done for this medicolegal case.

A collaborative evaluation of the cytotoxicity of two surfactants by using the human corneal epithelial cell line and the WST-1 test.

This study was undertaken to investigate the use of the in vitro test WST-1, an assay of cell proliferation and viability, for a preliminary safety evaluation of topical ophthalmic preparations. The cytotoxicity of two surfactants, benzalkonium chloride (BAC) and polyoxyethylene-20-stearyl ether (Brij78, PSE) was independently investigated in four laboratories in the EU by using an immortalized human corneal epithelial (HCE) cell line. The HCE cells were exposed to BAC and PSE for 5 min, 15 min, and 1 hour, and the results of the HCE-WST-1 tests were collected and compared. After one-hour exposure, the EC(50) values in BAC-treated cells in the presence of serum ranged between 0.0650 +/- 0.0284 (mean +/- SD) mM, and those in the absence of serum 0.0296 +/- 0.0081 mM. The corresponding values for PSE were 0.0581 +/-.0300 mM and 0.0228 +/-.0063 mM. There were variations in the results between different laboratories, with coefficients of variation ranging from 31 to 121%, mean 58%. The use of one-hour exposure time is to be preferred, and the elimination of serum in the culture medium is recommended to avoid both underestimation of toxic effects and variability of the test results.

Life-threatening respiratory failure following accidental infusion of polyethylene glycol electrolyte solution into the lung.

Functional fecal retention is the most common cause of encopresis in children. Hospitalization may be required to clear the bowel following failure of outpatient management. Although the safety and efficacy of polyethylene glycol electrolyte solution is well established in children older than 6 months (1), its use should be carefully monitored in patients with altered mental status or impaired airway protective reflexes. We report the accidental infusion of NuLytely into the lungs of an 11-year-old female patient who consequently developed life-threatening acute lung injury. She rapidly developed respiratory failure requiring emergent tracheal intubation and suctioning, followed by mechanical ventilation. Careful monitoring is needed to avoid this potential complication if polyethylene glycol solution is infused via a nasogastric tube.

Triethylene glycol poisoning treated with intravenous ethanol infusion.

INTRODUCTION: Poisoning with triethylene glycol has been rarely reported in humans. Triethylene glycol is thought to be metabolized by alcohol dehydrogenase to acidic products resulting in the production of a metabolic acidemia. Triethylene glycol metabolism has previously been shown to be inhibited by fomepizole (4-methyl pyrazole) administration. We report a case of triethylene glycol ingestion, presenting with a metabolic acidemia, treated with intravenous ethanol administration. CASE REPORT: A 23-year-old female presented to the emergency department approximately 1-1.5 hours following ingestion of a gulp of triethylene glycol (99%) brake fluid with coma (GCS-3) and metabolic acidemia (pH 7.03, PCO2 44 mm Hg, Bicarbonate 11 mmol/L, anion gap 30 mmol/L, serum creatinine 90 mumol/L). She was intubated and given 100 mmol of intravenous sodium bicarbonate. An ethanol loading dose was administered followed by an infusion to maintain serum ethanol at 100 mg/dL. Acidemia gradually resolved over the next 8 hours and she was extubated 12 hours later. The ethanol infusion was continued for a total of 22 hours. There was no recurrence of acidemia. Serum ethanol, ethylene glycol, and methanol levels were nondetectable on presentation, as was serum salicylate. Urine drug of abuse screen and thin-layer chromatography revealed no other coingested substances. The patient was discharged to a psychiatric ward 36 hours postingestion. CONCLUSION: Pure triethylene glycol poisoning results in coma and metabolic acidemia and may be treated with alcohol dehydrogenase inhibitors such as ethanol.

Intravenous 4-methylpyrazole as an antidote for diethylene glycol and triethylene glycol poisoning: a case report.

Diethylene glycol (DEG) intoxication resembles that of ethylene glycol, with progressive inebriation, anion gap metabolic acidosis, renal failure, coma and death. DEG is oxidized by alcohol dehydrogenase (ADH) to more toxic byproducts, thus blockade of ADH might be beneficial. Triethylene glycol (TEG), also metabolized by ADH, is less toxic. A young female suicidally ingested DEG and TEG, presenting in metabolic acidosis with coma. Given 4-methylpyrazole (4-MP), an ADH inhibitor, the acidosis resolved, the patient recovered and was discharged without sequelae. 4-MP, if supported by further studies, may be useful in DEG poisoning.

Acute renal toxicity after ingestion of Lava light liquid.

A 65-year-old man with a history of alcohol abuse and seizure disorder presented to the emergency department with altered mental status, increased anion gap acidosis, phenytoin toxicity, and acute kidney failure. The patient had ingested the liquid contents of a Lava light, which contained chlorinated paraffin, polyethylene glycol (molecular weight 200), kerosene, and micro-crystalline wax. Gas chromatography-mass spectrophotometry of the patient's blood produced results consistent with the same analysis of the Lava light contents. After 3 days of declining mental status and worsening kidney function, the patient required hemodialysis. After a prolonged hospitalization, the patient was discharged home with residual renal insufficiency. Although multifactorial, the associated renal toxicity was most probably related to the low molecular weight polyethylene glycol content of the lamp's liquid contents.