Awareness raising and dealing with methanol poisoning based on effective strategies.

Intoxication with methanol most commonly occurs as a consequence of ingesting, inhaling, or coming into contact with formulations that include methanol as a base. Clinical manifestations of methanol poisoning include suppression of the central nervous system, gastrointestinal symptoms, and decompensated metabolic acidosis, which is associated with impaired vision and either early or late blindness within 0.5-4 h after ingestion. After ingestion, methanol concentrations in the blood that are greater than 50 mg/dl should raise some concern. Ingested methanol is typically digested by alcohol dehydrogenase (ADH), and it is subsequently redistributed to the body's water to attain a volume distribution that is about equivalent to 0.77 L/kg. Moreover, it is removed from the body as its natural, unchanged parent molecules. Due to the fact that methanol poisoning is relatively uncommon but frequently involves a large number of victims at the same time, this type of incident occupies a special position in the field of clinical toxicology. The beginning of the COVID-19 pandemic has resulted in an increase in erroneous assumptions regarding the preventative capability of methanol in comparison to viral infection. More than 1000 Iranians fell ill, and more than 300 of them passed away in March of this year after they consumed methanol in the expectation that it would protect them from a new coronavirus. The Atlanta epidemic, which involved 323 individuals and resulted in the deaths of 41, is one example of mass poisoning. Another example is the Kristiansand outbreak, which involved 70 people and resulted in the deaths of three. In 2003, the AAPCC received reports of more than one thousand pediatric exposures. Since methanol poisoning is associated with high mortality rates, it is vital that the condition be addressed seriously and managed as quickly as feasible. The objective of this review was to raise awareness about the mechanism and metabolism of methanol toxicity, the introduction of therapeutic interventions such as gastrointestinal decontamination and methanol metabolism inhibition, the correction of metabolic disturbances, and the establishment of novel diagnostic/screening nanoparticle-based strategies for methanol poisoning such as the discovery of ADH inhibitors as well as the detection of the adulteration of alcoholic drinks by nanoparticles in order to prevent methanol poisoning. In conclusion, increasing warnings and knowledge about clinical manifestations, medical interventions, and novel strategies for methanol poisoning probably results in a decrease in the death load.

Effects of methanol and formic acid on CRYB, ALDH2, and ATP5A1 of RGCs.

OBJECTIVE: To explore the toxicity of methanol and its metabolite, formic acid on αB-crystallin(CRYB), aldehyde dehydrogenase (ALDH2), and ATPsynthase (ATP5A1) of rat retinal ganglion cells (RGCs). METHODS: RGCs are cultured in vitro in a toxic environment with 15/30/60 mM methanol or formic acid, respectively. Then, the morphological changes of RGCs and protein and mRNA levels of ALDH2, ATP5A1, and CRYB in rat RGCs were evaluated. RESULTS: 1) Compared to the toxicity of 15 mM formic acid on RGCs, 30 mM of formic acid environment significantly promoted apoptosis, and cell death occurred in the 60-mM formic acid group 24 h later. The toxicity of methanol for inducing apoptosis was not as obvious as formic acid. 2) In the 15-mM group, the level of CRYB protein was down-regulated after stimulating with both methanol and formic acid for 48 h, and ATP5A1 protein level decreased significantly with formic but not methanol. No change in ALDH2 was observed in methanol or formic acid. With a prolonged duration (>7 d) or high concentration (>30 mM) stimulation, cells treated with both methanol and formic acid showed severe apoptosis, rendering it challenging to collect a sufficient number of cells for protein detection. 3) In the 48-h group, no significant effect was detected on the mRNA of CRYB, ATP5A1, and ALDH2 by both 15/30 mM formic acid and 15 mM methanol. Conversely, 30 mM methanol had a significant up-regulation effect on the expression of the three genes, while no significant effect was observed in the 7-d groups. CONCLUSIONS: Formic acid exerted stronger toxicity on CRYB, ATP5A1, and ALDH2 than methanol and played a regulatory role at the translation level, while the effect of methanol is still uncertain, needing additional investigation.

Methanol in unrecorded fruit spirits. Does it pose a health risk to consumers in the European Union? A probabilistic toxicological approach.

Methanol is present at high concentrations in unrecorded fruit spirits, placing consumers of these beverages at risk of exposure at high levels. When assessing any health risk it is necessary to consider blood methanol levels (BMLs), reference dose (RfD), and maximum tolerable blood methanol level (MTBML). The aim of our study was to estimate daily methanol intake and related BMLs attributable to drinking unrecorded fruit spirits in the European population using a probabilistic Monte Carlo simulation. Data on the concentration of methanol in unrecorded fruit spirits in European Union member states were collected and the health risk posed by consumption of unrecorded fruit spirits was estimated. We found that drinking unrecorded fruit spirits containing methanol at a concentration higher than 8598.1 mg/litre of pure alcohol (p.a.) or 6382.1 mg/litre of p.a. and also at least 10 g ethanol can result in a methanol intake above the RfD by men and women, respectively. We confirmed that consumption of unrecorded fruit spirits containing methanol does not result in BMLs higher than the MTBML. Further studies are required to assess whether there is any health risk from chronic exposure to methanol above the RfD from unrecorded fruit spirits.

The outbreak of methanol intoxication during COVID-19 pandemic: prevalence of brain lesions and its predisposing factors.

During the COVID-19 pandemic, methanol-containing beverages' consumption has risen because people mistakenly believed that alcohol might protect them against the virus. This study aimed to evaluate the prevalence and predisposing factors of brain lesions in patients with methanol toxicity and its outcome. A total of 516 patients with confirmed methanol poisoning were enrolled in this retrospective study, of which 40 patients underwent spiral brain computed tomography (CT) scan. The presence of unilateral or bilateral brain necrosis was significantly higher in the non-survival group (p = 0.001). Also, intracerebral hemorrhage (ICH) and brain edema were prevalent among patients that subsequently died (p = 0.004 and p = 0.002, respectively). Lower Glasgow Coma Scale (GCS) was related to a higher mortality rate (p = 0.001). The mortality rate in chronic alcohol consumption was lower than the patients who drank alcohol for the first time (p = 0.014). In conclusion, increasing the number of methanol poisoning and its associated mortality and morbidity should be considered a threat during the COVID-19 pandemic.

Severe Optic Disc Cupping Following the Methanol Toxicity in a 20-Year-old Man: A Case Report.

In April 2018, a 20-year-old man with a history of methanol intoxication from an alcoholic drink two years ago, when he was 18 years old, was referred to Nikookari Eye Hospital in Tabriz, Iran. He was admitted to emergency service and underwent eight hours of hemodialysis at the time of poisoning. His past medical history was negative, and he did not take any medication after discharge. The patient had a driving license and never experienced any visual problems before. At presentation, his visual acuity was 160/200 in both eyes with the main complaint of visual field deterioration. Other neurologic exams and brain magnetic resonance imaging (MRI) were reported normal by a neurologist. Optic disc cupping was near total in both eyes with a very narrow remaining rim. Optic disc cupping was very similar to glaucomatous cupping. Intraocular pressure was checked several times via Goldmann tonometry and was 13 mmHg. There was no history of refractive surgery leading to thin cornea. Based on this case, methanol poisoning can mimic glaucomatous optic disc cupping. This is the first case report of methanol toxicity-related optic disc cupping from Iran.

Inpatient Burden and Mortality of Methanol Intoxication in the United States.

BACKGROUND: This study aimed to assess inpatient prevalence, characteristics, outcomes, and resource utilization of hospitalization for methanol intoxication in the United States. MATERIALS AND METHODS: A total of 603 hospitalized patients with a primary diagnosis of methanol intoxication from 2003 to 2014 were identified in the National Inpatient Sample database. The inpatient prevalence, clinical characteristics, treatments, outcomes, resource utilization, were investigated. Multivariable logistic regression was performed to identify factors independently associated with in-hospital mortality. RESULTS: The overall inpatient prevalence of methanol intoxication among hospitalized patients was 6.4 cases per 1,000,000 admissions in the United States. The mean age was 38±18 (range 0-86) years. 44% used methanol for suicidal attempts. 20% of admissions required mechanical ventilation, and 40% required renal replacement therapy. The three most common complications were metabolic acidosis (44%), hypokalemia (18%), and visual impairment or optic neuritis (8%). The three most common end-organ failures were renal failure (22%), respiratory failure (21%), and neurological failure (17%). 6.5% died in the hospital. Factors associated with increased in-hospital mortality included alcohol drinking, hypernatremia, renal failure, respiratory failure, circulatory failure, and neurological failure. The mean length of hospital stay was 4.0 days. The mean hospitalization cost per patient was $43,222 CONCLUSION: The inpatient prevalence of methanol intoxication in the United States was 6.4 cases per 1,000,000 admissions. The risk of in-hospital mortality mainly depended on the number of end-organ failures.

Promoting Lignin Valorization by Coping with Toxic C1 Byproducts.

The toxic C1 compounds methanol and formaldehyde are generated during bioconversion of lignin into value-added chemicals. These toxins can be detoxified and assimilated by methylotrophs to synthesize useful metabolites and cell biomass. We discuss the promising future of constructing integrated biosystems to use toxic C1 byproducts and promote lignin valorization.

The effect of ranitidine administration in graded dosage to the degree of liver damage: A study on Wistar rats with acute methanol intoxication.

The high incidence of alcoholic poisoning in Indonesia is caused by the use of methanol as a surrogate ingredient of nonconforming alcohol. The product of methanol metabolism is toxic to the liver. Ranitidine has been studied as an antidote to reduce the effect of methanol toxicity. The present study aimed to assess the effect of ranitidine administration on the liver damage of Wistar rats with acute methanol intoxication. This research was an experimental study with randomized and posttest-only control group design. A total of 24 male Wistar rats divided into four groups, each consisting of six Rats. The control group (K0) served as a reference normal value. The control group (K1) was intoxicated with methanol 7 g/kg body weight (b.w.) through rat gavage tube. Treatment groups were intoxicated with methanol and 15 minutes after that, Ranitidine (30 mg/kg b.w. (P1) or 60 mg/kg b.w. (P2)) was given intraperitoneally. Ranitidine administration was proven to protect the liver tissue from damage due to methanol intoxication as was indicated from the histopathological examination. Ranitidine with dose 60 mg/kg b.w. is better in reducing the degree of liver tissue damage in acute methanol intoxication rats.

Late leukoencephalopathy in patients with methanol intoxication / Leucoencefalopatía tardía posterior a intoxicación por metanol

No disponible

Potential methanol toxicity and the importance of using a standardised alcohol-based hand rub formulation in the era of COVID-19.

OBJECTIVES: Hand sanitisers are urgently needed in the time of COVID-19, and as a result of shortages, some people have resorted to making their own formulations, including the repurposing of distilleries. We wish to highlight the importance of those producing hand sanitisers to avoid methylated spirits containing methanol and to follow WHO recommended formulations. METHODS: We explore and discuss reports of methanol toxicity through ingestion and transdermal absorption. We discuss the WHO formulations and explain the rationale behind the chosen ingredients. SHORT CONCLUSION: We advise those producing hand sanitisers to follow WHO recommended formulations, and advise those producing hand sanitisers using methylated spirits, to avoid formulations which contain methanol.

A review of methanol poisoning: a crisis beyond ocular toxicology.

At first blush, methanol poisoning may be seen as an arcane problem generally associated with rapid ocular neuropathy. The emerging clinical reality is that methanol poisoning around the globe has claimed increasingly large numbers of deaths largely due to the press of poverty and the delay in suspecting and diagnosing methanol toxicity. With the onset of the COVID-19 pandemic, false beliefs about methanol's preventive potential vs viral infection of have arisen. In March of this year, more than 300 Iranians died and 1000 became ill after consuming methanol in the hope that it would protect them against the novel coronavirus. We review the context and magnitude of methanol toxicity, pathophysiology, principal medical issues, and human variability in metabolism. While toxicologists and clinicians may need to be especially attentive to this problem, it is becoming clear that the social and economic underpinnings of the methanol poisoning crisis must be actively and urgently explored and managed as vigorously as its toxicologic and pathophysiologic components.

Transdermal Methanol Intoxication.

Methanol is a clear liquid with high toxicity. Methanol intoxication may result from accidental exposure, overconsumption of compounds containing methanol with suicidal intent, or following consumption of distilled and contaminated alcoholic beverages. This report describes a case of transdermal methanol intoxication, which is a rare condition. A 58-year-old woman presented with nausea, vomiting, weakness, diplopia and dizziness. On neurological examination, she only had diplopia. On physical examination, a hyperemic lesion with clear borders was found over the right knee. The patient's recent medical history revealed that four days prior to the onset of symptoms, she had covered her knee with a methanol-soaked bandage in an attempt to alleviate her knee pain. She had a high osmolar gap as well as high anion-gap metabolic acidosis (HAGMA). Methanol intoxication was suspected due to HAGMA and high osmolar gap. Serum methanol levels were subsequently measured and found to be 37.9 mg/ dL. The patient was treated with intravenous (IV) bicarbonate, IV ethyl alcohol and hemodialysis. She was discharged with no central nervous system or ophthalmologic sequelae. Methanol poisoning should be kept in mind in patients with diplopia and unexplained metabolic acidosis. Although most methanol intoxication cases occur after oral ingestion, it should be considered that methanol poisoning may occur transdermally.

Revisions to Limits for Methanol in the Air of Spacecraft.

INTRODUCTION: The previous Spacecraft Maximal Allowable Concentrations (SMACs) for methanol were established by characterizing minor effects upon cognitive functions as a no-observable adverse effects level (NOAEL). However, an increasing awareness of the risk posed by Space-Associated Neuro-ocular Syndrome (SANS) has caused NASA Toxicology to reexamine SMACs for methanol because exposure to it can also adversely affect ocular health. An updated review of the literature indicates that no adjustments to the SMACs due to SANS complications were required, while confirming that effects upon the central nervous system remain the appropriate basis for the SMACs for methanol. Our review, however, identified several issues that provide justification for modest SMAC reductions. It has recently been recognized that inhaled methanol may reach the brain via the olfactory system and be absorbed there into the highly toxic metabolite formaldehyde. A benchmark dose (BMD) for an extra risk of 10%, derived from an analysis of the incidences of neurological lesions in monkeys chronically exposed to methanol, is an order of magnitude less than the Environmental Protection Agency's (EPA's) reference concentration for chronic inhalation of methanol. Reports calling attention to the relative insensitivity of traditional methods of assessing cognitive function erode confidence that adverse effects at the concentration reported as a NOAEL would have been recognizable. Therefore, an additional modest safety factor of three is applied to SMACs for methanol.Scully RR, Garcia H, McCoy JT, Ryder VE. Revisions to limits for methanol in the air of spacecraft. Aerosp Med Hum Perform. 2019; 90(9):807-812.

Effect of taxifolin on methanol-induced oxidative and inflammatory optic nerve damage in rats.

Purpose: Oxidative stress and inflammation have been demonstrated in the pathogenesis of methanol toxicity. Taxifolin has antioxidant and anti-inflammatory properties. In this study, we examined the protective effect of taxifolin against methanol-induced optic nerve toxicity. Materials and methods: Animals were divided into four groups (n = 6): healthy control group (HG), methotrexate (MTX) treated group, methotrexate + methanol treated group (MTX + M), and methotrexate + methanol + taxifolin treated group (MTX + M+T). MTX was administered to all groups except HG group 3 mg/kg via oral gavage for 7 d. After that 20% methanol was orally administered to the MTX + M and MTX + M+T group at a dose of 3 g/kg. After 4 h, taxifolin was orally administered to MTX + M+T group 50 mg/kg. Animals were sacrificed by high-dose thiopental anaesthesia, 8 h after taxifolin administration and biochemical studies were performed. Results: Malondialdehyde (MDA), total oxidant system, nuclear factor kappa B (NF-κB), and tumour necrosis factor-alpha levels were significantly higher in the optic nerve of MTX and MTX + M groups compared to HG group. Otherwise, total glutathione (tGSH) and total antioxidant system levels decreased in MTX and MTX + M groups according to the HG group. MDA, total oxidant system, NF-κB, and tumour necrosis factor-alpha levels were decreased in the MTX + M+T group and tGSH, and total antioxidant system levels increased in the MTX + M+T group according to the MTX + M group. Conclusions: These results indicate that taxifolin prevents oxidative and inflammatory optic nerve damage due to methanol exposure.

Acute kidney injury and the risk of mortality in patients with methanol intoxication.

BACKGROUND: Methanol poisoning is a serious public health issue in developing countries, but few data are available in the literature on acute kidney injury (AKI) after methanol intoxication. METHODS: This study examined the clinical features, spectrum and outcomes of AKI in patients with methanol intoxication and evaluated the predictors of mortality after methanol intoxication. A total of 50 patients with methanol intoxication were seen at Chang Gung Memorial Hospital between 2000 and 2013. Patients were grouped according to the status of renal damage as AKI (n = 33) or non-AKI (n = 19). Demographic, clinical, laboratory, and mortality data were obtained for analysis. RESULTS: Most patients were middle-aged (47.8 ± 14.9 years), predominantly male (74.0%), and habitual alcohol consumers (70.0%). Most incidents were oral exposures (96.0%) and unintentional (66.0%). Two (4.0%) patients attempted suicide by intravenous injection of methanol. Five (10.0%) patients suffered methanol intoxication after ingestion of methomyl pesticide that contained methanol as a solvent. Compared to non-AKI patients, the AKI patients were older (50.9 ± 13.7 versus 41.6 ± 15.6 years, P = 0.034), predominantly male (90.9% versus 42.8%, P = 0.000), more habitual alcohol users (84.8% versus 41.2%, P = 0.001) and had more unintentional exposures (82.8% versus 35.3%, P = 0.001). Furthermore, there was a higher incidence of respiratory failure (63.6% versus 29.4%, P = 0.022) in the AKI group than in the non-AKI group, respectively. The laboratory studies revealed that the AKI patients suffered from more severe metabolic acidosis than the non-AKI patients. By the end of this study, 13 (39.5%) AKI patients and 1 (5.9%) non-AKI patient had died. The overall in-hospital hospital mortality rate was 28%. In a multivariate binary logistic regression model, it was demonstrated that AKI (odds ratio 19.670, confidence interval 1.026-377.008, P = 0.048) and Glasgow coma scale score (odds ratio 1.370, confidence interval 1.079-1.739, P = 0.010) were significant factors associated with mortality. The Kaplan-Meier analysis disclosed that AKI patients suffered lower cumulative survival than non-AKI patients (log-rank test, chi-square = 5.115, P = 0.024). CONCLUSIONS: AKI was common (66.0%) after methanol intoxication and was predictive of in-hospital hospital mortality. The development of AKI was associated with a 19.670-fold higher risk of in-hospital mortality.

A Combinational Approach of Enhanced Methanol Production and Double Bt Genes for Broad Spectrum Insect Resistance in Transgenic Cotton.

The prevalence of insect resistance against Bt toxins has led to the idea of enhancing demethylation from cell wall pectin by pectin methylesterase enzyme for overproduction of methanol which is toxic to insects pests. The AtPME and AnPME fragments ligated into pCAMBIA1301 vector were confirmed through restriction digestion with EcoR1 and BamH1. Excision of 3363 bp fragment from 11,850 bp vector confirmed the ligation of both fragments into pCAMBIA1301 vector. Transformation of pectin methylesterase-producing genes, i.e., AtPME and AnPME from Arabidopsis thaliana and Aspergillus niger cloned in plant expression vector pCAMBIA1301 under 35S promoter into cotton variety CEMB-33 harboring two Bt genes Cry1Ac and Cry2A, respectively, was done by using shoot apex-cut Agrobacterium-mediated transformation method. The plantlets were screened on MS medium supplemented with hygromycin on initial basis. Amplification of 412 and 543 bp, respectively, through gene-specific primer has been obtained which confirmed the successful introduction of pCAMBIA AtPME and AnPME genes into cotton variety CEMB 33. Relative expression of AtPME and AnPME genes through real-time PCR determined the expression level of both gene ranges between 3- and 3.5-fold in different transgenic cotton lines along with quantity of methanol ranging from 0.8 to 0.9% of maximum while 0.5% to 0.6% of minimum but no expression was obtained in negative non-transgenic control cotton plant with least quantity of methanol, i.e., 0.1%. Almost 100% mortality was observed in insect bioassay for Helicoverpa armigera on detached leaves bioassay and 63% for Pink Bollworm (Pectinophora gossypiella) on growing transgenic cotton bolls as compared to positive control transgenic cotton with double Bt genes where mortality was found to be 82% for H. armigera and 50% for P. gossypiella while 0% in negative control non-transgenic plants.

Toxic effects of a methanolic coal dust extract on fish early life stage.

Coal dust is a contaminant that impacts the terrestrial and aquatic environment with a complex mixture of chemicals, including PAHs and metals. This study aims to evaluate the toxic effect of a methanolic coal dust extract on a fish early life stage by analyzing phenotypic alterations, transcriptome changes, and mortality in zebrafish (ZF) embryos. ZF embryos were exposed to methanolic coal dust extract at 1-5000 mg·L-1 and monitored using bright field microscopy 24 and 48 hpf to determine malformations and mortality. In situ hybridization, RNA sequencing, and qRT-PCR were employed to identify transcriptome changes in malformed embryos. Three malformed phenotypes were generated in a dose-dependent manner. In situ hybridization analysis revealed brain, somite, dorsal cord, and heart tube development biomarker alterations. Gene expression profile analysis identified changes in genes related to structural constituent of muscle, calcium ion binding, actin binding, melanin metabolic process, muscle contraction, sarcomere organization, cardiac myofibril assembly, oxidation-reduction process, pore complex, supramolecular fiber, striated muscle thin filament, Z disc, and intermediate filament. This study shows, for the first time, the malformations generated by a mixture of pollutants from a methanolic coal dust extract on a fish early life stage, constituting a potential risk for normal embryonic development of other aquatic vertebrate organisms. Furthermore, we establish that phenotypes and changes in gene expression induced by the extract constitute a target for future studies about mechanical toxicity and their utility as sensitive tools in environmental risk assessments for biota and humans exposed to coal mining activities.

Strong insecticidal potential of methanol extract of Ferulago trifida fruits against Anopheles stephensi as malaria vector.

Many researchers have focused on controlling pest insects and vectors by natural products because of their low environmental pollution. The present study was conducted to evaluate the antioxidant and larvicidal activities of chloroform and methanol extracts of the leaves, fruits, roots, and isolated coumarin compounds (prantschimgin, oxypeucedanin, and 6-hydroxymethylherniarin) of Ferulago trifida from the Apiaceae family against Anopheles stephensi as one of the main malaria vectors. For insecticidal evaluation, A. stephensi larvae were exposed to different concentrations of the extracts and pure compounds (0.625-1280 ppm) according to the WHO protocol. The mortality percentages were measured 24 h after treatment and lethal concentration values were calculated. In addition, radical scavenging activities of the mentioned extracts and compounds were measured by the DPPH method. The methanol extract of fruits showed potent insecticidal properties with LC50 and LC90 values of 2.94 and 18.12 ppm, respectively. The chloroform extracts of the fruits and leaves were the second and third extracts with larvicidal effects. Among pure compounds, only oxypeucedanin showed moderate toxicity against A. stephensi with LC50 and LC90 values of 116.54 and 346.41 ppm, respectively. The antioxidant activities of the methanol extracts of leaves and fruits were stronger than other extracts with IC50 values of 155.83 and 159.32 ppm, respectively. In conclusion, the methanol extract of F. trifida fruits can be used as a potent bio-insecticide in green control programs of mosquitoes, especially A. stephensi.