Exposure of High Concentration of Methanol Vapor for Neurological Intoxication in Factory Workers

Exposure of High Concentration of Methanol Vapor for Neurological Intoxication in Factory Workers | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Short Report Exposure of High Concentration of Methanol Vapor for Neurological Intoxication in Factory Workers Chan-Seok Moon This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3407340/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background A few studies of biological monitoring of MeOH vapor exposure focused on human subjects were thought to have been reported until 2000. After that until current, the study of MeOH vapor exposure concentration and neurological toxicity as the dose-response relationship for biological monitoring has not been fully studied. Objective The study aims to reasonable estimate the step-by-step methanol concentration of neurological toxicity from respiratory exposure in workers. Methods The methanol exposure was constituted to focus on respiratory air and symptoms. The previous reports were searched for dose-response relation between methanol vapor concentration and urinary methanol concentration and between methanol vapor concentration and symptoms for representative methanol exposure. Google Scholar (including Korean reports) and PubMed from 1980 to 2023 present were examined as search engines. Results Respiratory methanol exposure 93 ppm to 200 ppm of vapor concentration (TLV-TWA of ACGIH) did not show clear symptoms. And their corresponding urinary methanol showed 22 to 42 ppm. Exposure to 459 ppm of vapor was reported to be the symptom of dimmed vision which was the lowest concentration indicating optic nerve disorder. In the 1025.0 ppm of vapor, optic nerve disorders and central nerve disorders occurred. Conclusions Respiratory methanol exposure had initiated clinical symptoms as optic nerve toxicity from 459.0 ppm at the vapor phase. In the 1025.0 ppm of vapor, representative symptoms were identified such as optic nerve, and central nerve disorders. methanol vapor exposure inhalation symptoms Background In fact, methanol (MeOH) is an extraordinarily toxic substance to the nervous system beyond imagination. However, the toxicity of MeOH is not well known except for the classical and general hazard information that can lead to blindness if drunk. Furthermore, little information has been known so far about toxicity through inhalation exposure to MeOH vapor [ 1 ]. The MeOH can be easily absorbed from the exposure route of respiration and skin [ 2 ]. The two exposure routes of MeOH are important to the workers who are using MeOH in the workshop [ 3 ]. To respiratory monitoring, Pulmonary MeOH exposure is known that approximately 56–82% of the total respiratory intake at the end of a work shift. Biological monitoring from exposure indices such as human blood and urine can be monitored for MeOH exposure from the environment. Of the total exposed MeOH in workers, elimination was known via exhaling or urination for approx. 10% of unmetabolized MeOH. Absorption in the body is 70–80% of the MeOH then is metabolized as formaldehyde through alcohol dehydrogenase and then transformed into free radicals and formic acid in the liver and red blood cells, resulting in the final products of carbon dioxide and water through formyl tetrahydrofolate synthetase [ 2 , 4 ]. MeOH toxicity has symptoms of the central nervous system, metabolic acidosis, vision loss, and gastrointestinal symptoms which are caused by the metabolites from MeOH exposure [ 1 , 3 , 5 ]. The metabolic acidosis level was related to the severity of the toxicity of MeOH. Namely, formic acid from the acidosis of formate from MeOH might cause ocular damage as acute poisoning [ 6 , 7 ]. If MeOH is simultaneously exposed to other chemicals such as ethanol [ 8 , 9 ], isopropanol [ 10 ], or methyl ethyl ketone [ 11 ], it is possible to show a positive or negative effect on the MeOH poisoning [ 12 , 13 ]. Many useful studies about biological monitoring for MeOH exposure were thought to be reported until 2000 year. After that until current, the study for MeOH exposure as biological monitoring has not been fully studied. MeOH intoxication has been very high, although the chemical structure was very simple, and has not well known the chemical toxicities until the chemical accident in Korean manufacturing companies of smartphone parts. These companies were manufacturing smartphone side buttons and panels through an aluminum CNC (Computerized Numerical Control) cutting process. Recent reports for MeOH exposure were usually approached to focus on an epidemiological and medical study of the Korean accident of CNC process and inhalational accident from misuse during the COVID-19 pandemic [ 3 , 14 – 17 ]. However, reports have been very rare about exposure dose and responses for biological indices or neurological symptoms for the toxicities. Therefore, the study tried to dose-response relation with background concentration level, near 200 ppm of TLV-TWA of ACGIH, over 1000 ppm of MeOH as exposure dose, and their representative symptoms of MeOH as the response. Methods Research reports of MeOH exposure published in Google Scholar (including Korean reports) and PubMed from 1980 to 2023 present were examined. To investigate MeOH exposure, the clinical symptoms, and biological monitoring data, exposure status, and symptoms for representative methanol exposure were identified in searches using the keywords ‘methanol’ and ‘exposure’. Among the papers, 40 papers from Google Scholar (from SCI-grade medical science journals) and PubMed were available articles for this study after review. All references included reports from international and domestic authorized public institutions. From the published reports, at first, the human (workers or volunteer) MeOH exposure concentration was identified and collected with exposure status such as co-exposed chemicals, exposure period, symptoms, biological indices data as urinary MeOH concentration, and subject general information as gender, age, MeOH working period if possible. Special attention was paid to the recent MeOH vapor exposure accident in South Korea because that had comparatively clearer information for clinical symptoms from MeOH vapor exposure concentration, exposure status, and symptoms for representative MeOH exposure [ 3 , 14 , 15 , 18 , 19 ]. Results Exposure sources and biological indices in the general population at the background level of MeOH The general population has a low-level exposure to MeOH through the dietary intake of vegetables, fruits, beverages, and local traditional liquors [ 16 , 17 , 20 – 22 ]. Vegetable juice has 12–640 mg/L of MeOH, and fruits have about 140 mg/L. Fermented beverages have 1,500 mg/L or more. Alcoholic beverages such as local traditional liquor, Korean wine, whiskey, and vodka contain a considerable amount of MeOH [ 22 , 23 ]. As respirational exposure, smoking a cigarette is about 180 µg MeOH as vapor phase. Aspartame as an artificial sweetener is converted into MeOH about 10% when hydrolyzed in the human body [ 4 ]. Biological indices, in the Japanese population had that the urinary MeOH is in most cases less than 2 mg/L on the background exposure monitoring survey. The Urinary MeOH concentration was reported as 0.73 mg/L, 1.1 mg/L, 1.34 mg/L, 1.7 mg/L of GM. [ 4 , 24 – 27 ]. In the Brazilian survey, urinary MeOH was 2.1 mg/L of GM [ 28 ]. Exposure of MeOH vapor below 200 ppm of TLV-TWA and symptoms Table 1 shows the MeOH concentration of respiratory air and exposure status including urinary concentrations, subjects, exposure term, co-exposure chemical, and symptoms. Respiratory MeOH was available from 93 ppm to 200 ppm. And their corresponding urinary MeOH showed 22 to 42 ppm. MeOH from ambient air and urinary concentration of MeOH was thought to be a linear relationship [ 13 ]. Subjects were both workers and volunteers for exposure study of low-level MeOH. The exposure status of MeOH was constituted to exposure single chemical as MeOH which was not affected by other influential solvents like ethanol [ 8 , 9 ], isopropanol [ 10 ], methyl ethyl ketone [ 11 ]. Almost all workers had chronic exposure to MeOH. A symptom of MeOH exposure was a subclinical reaction of nasal respiratory mucosa [ 29 ]. Table 1 Exposure of MeOH vapor below the 200 ppm and exposure status and symptoms Respiratory MeOH (mg/L) Urinary MeOH (mg/L) Subjects Exposure term Co-exposure Symptoms Remarks 93 22 workers Chronic single - [ 25 ] 107 - workers - - no [ 35 ] 120 36 workers Chronic single - [ 24 ] 152 40 workers Chronic single - [ 25 ] 181 74 volunteer Acute single no [ 36 ] 191 - volunteer Acute single no [ 37 ] 200 40 workers Chronic single - [ 25 ] 200 42 workers Chronic single - [ 26 ] 200 - volunteer Acute single no [ 38 – 40 ] 200 - volunteer Acute single Subclinical reaction of nasal respiratory mucosa [ 29 ] Exposure to MeOH of respiratory air over 200 ppm and symptoms In Table 2 , the concentration of methanol vapor could be confirmed at 249 ppm to 459 ppm. A total of three papers were confirmed in workplace workers using methanol, and in these cases, the symptoms were caused by chronic exposure. These reports targeted methanol vapor with single substance exposure, not mixtures. Exposure to 200 ppm level in the respiratory air (in Table 1 ), there was no symptom or showed to subclinical reaction of natural respiratory mucosa. Following 249 ppm exposure in the study volunteers showed weak fatigue [ 4 ]. At 287.5 ppm of median (200–375 ppm), recurrent headaches were shown [ 30 ]. Exposure to 459 ppm reported ‘dimmed vision’ and ‘nasal irritation’ [ 26 ]. In the case of this concentration, it was the lowest concentration indicating optic nerve disorder among the reports that were confirmed to date. Table 2 MeOH exposure level and status from ambient air and neurological symptoms Ambient air (ppm) Subjects Exposure term Co- exposure Symptoms Remarks 249.0 volunteer Acute single weak fatigue [ 4 ] 287.5 * workers Chronic single recurrent headaches [ 30 ] 459.0 workers Chronic single dimmed vision, nasal irritation [ 26 ] *; median for 200–375 ppm. Exposure of MeOH over 1000 ppm in respiratory air and symptoms In Table 3 , typical central nervous system disorders and optic nerve disorders of MeOH exposure were identified at concentrations of 1000 ppm or higher. The atmospheric concentration in which optic nerve disorders and central nerve disorders clearly occur was reported as 1025.0 ppm. At that exposure level, blurred vision, and eye irritation, which appear to be optic nerve disorders, were identified. The exposure sources were ink components of the spirit duplicator, and mixed organic solvents such as ethanol or isopropyl alcohol were exposed in addition to methanol [ 31 ]. Table 3 MeOH exposure level and status from ambient air and neurological symptoms Ambient air (ppm) Subjects Exposure term Co-exposure Symptoms Remarks 1025.0 workers Chronic mixture blurred vision, eye irritation, headache, dizziness, and nausea [ 31 ] 1625.3* (1030.1-2220.5) workers Sub-chronic single amblyopia, binocular optic neuritis, visual dimness, blindness, vomiting, difficulty breathing, loss of pupillary reflex, metabolic encephalopathy, vomiting and decreased consciousness [ 3 , 14 , 15 , 19 ] 1707.5 workers Chronic single headaches, dizziness and eye irritation, blurred vision, and nausea/upset stomach [ 4 ] 1722.5* (365–3080) workers Chronic single blurred vision, Headache, Dizziness, Nausea [ 32 ] 6636.3 workers Acute mixture depression, nausea, vomiting, shortness of breath, photophobia decreased visual acuity [ 33 ] 8300 - - - Temporary blindness [ 34 ] *; as median Exposure with a median of 1625.3 ppm of exposure level (1030.1-2220.5 ppm range) mostly showed typical symptoms of methanol exposure. The exposure occurred in the CNC cutting process which was one of the works of lathe with computerized numerical control for high precision work. The smartphone panel and its buttons were made by the CNC cutting process from aluminum material. During the process, MeOH is sprayed on the cutting side as a surface emulsifier. At that time, spread MeOH was evaporated inside the workshop. When the manufacturing of the smartphone side button is completed, the MeOH on the surface of the side button is removed using a high-pressure air blower (Korean usually called an air gun), which also evaporates a large amount of MeOH into the atmosphere of the workplace. These companies had not completely operated a ventilation system with the third subcontractor of a large electronics company in Korea which was not sufficiently controlled by Korean law [ 3 , 18 ]. In the exposure concentration, most of the symptoms related to optic nerve disorders and central nervous system disorders were reported. It was very precisely evaluated to exposure accidents of hazardous chemicals in the workshop of Korea because exposure accidents of chemicals in respiratory air usually had difficulty in identifying their exposure level. The accident was that the use of ethanol was recommended in the CNC device usage manual, but it was caused by arbitrarily changing this ethanol to methanol. Since these accidents occurred at workplaces using a single methanol substance, a close epidemiological investigation was conducted by the Korean Ministry of Labor, and based on this, the exposure concentration of the indoor working environment was confirmed. All methanol-using workers report that it was caused by sub-chronic exposure [ 3 , 18 , 19 ]. Similar to this report, the disorder was shown by chronic exposure to a single methanol substance reported by IPCS [ 4 ]. In the case of median 1722.5 ppm vapor exposure, workers' chronic exposure to single methanol showed no difference from the symptoms in the 1707.5 ppm concentration range at 1025.0 ppm reported earlier [ 32 ]. As the highest concentration according to these symptoms identified in the report, the highest concentration in exposure accidents in Korea was 2220.5 ppm [ 3 ]. In a study reported by Frederick et al., it was 3080 ppm [ 32 ]. Frenia and Schauben reported 6636.6 ppm methanol exposure which is acute and is a case of mixture exposure caused by intentional inhalation of CARB-MEDIC carburetor container toluene (43.8%), methanol (23.2%), methyl, and propane (12%) [ 33 ]. Temporary blindness was reported due to the exposure concentration in the atmosphere of 8300 ppm [ 34 ]. However, symptoms of blindness were also reported at 1625.3 ppm previously, so it could occur even at low concentrations of 8300 ppm or less. Discussion Vapor exposure of 459 ppm concentration (Table 2 ) showed dimmed vision and nasal irritation by Kawai et al. [ 26 ]. In the case of this concentration, it was estimated carefully the lowest concentration indicated optic nerve disorder among the previous reports. The subject was mainly workers who use MeOH in their workshop and were exposed chronically to MeOH vapor as single chemical, not a solvent mixture. This exposure concentration was important because of adjacent to 200 ppm of TLV-TWA and 250 ppm of STEL by ACGIH. The exposure concentration 459 ppm was near the TLV-TWA and STEL which was 2.3 folds higher than the TLV-TWA and 1.8 folds higher than the STEL. Then, blurred vision and eye irritation related to optic nerve disorder were identified at 1025 ppm of Table 3 . About the concentration range of 459 to 1025 ppm, the author, unfortunately, couldn’t identify reports of methanol exposure worker and their symptoms. Vapor exposure range of 1025 ppm to 1755.5 ppm had clearly occurred the MeOH symptoms of optic nerve disorders and central nerve disorders. For the assistance to this exposure range, the exposure concentration of 1625.3 ppm could play a pivotal role in proving symptom occurrence. These 1625. 3 ppm exposure had a range of 1030.1 to 2220.5 ppm. And symptoms showed amblyopia, binocular optic neuritis, visual dimness, blindness, vomiting, difficulty breathing, loss of pupillary reflex, metabolic encephalopathy, vomiting, and decreased consciousness. These were involved in almost representative MeOH exposure symptoms. At that focus, these Korean reports had somewhat more special findings than previous reports. 1025 ppm had very close to 1030.1 ppm (in minimum exposure concentration of 1625.3 ppm) of the median of Korean MeOH accident reports[ 3 , 18 , 19 ]. And 1707.5 ppm MeOH exposure report[ 4 ] was very near to 1625.3 ppm and was thought to be a reference value to assist the Korean MeOH accident report. 1722.5 ppm had 365–3080 ppm of wide exposure concentration range[ 32 ]. The symptoms of the exposure concentration (1722.5 ppm) were also related symptoms with the Korean MeOH accident report. For a more precise exposure condition, the working records of the two workers were identified. The two workers in Table 4 had mainly worked overtime for 12 hours of working at the companies and were exposed to 99.9% of extra-pure grade MeOH [ 14 , 19 ]. The two workers were formally reported by the Ministry of Employment of Labor in Korea that their neurological symptom was from MeOH vapor exposure at the workplace. Worker 1, worked for 3 months and 17 days from Sep. 21, 2015, to Jan 16, 2016. She showed vomiting before to shiftwork at 21 pm on Jan. 15, 2016, then went to the hospital for consulting and had blood tests. However, the cause for the symptoms could not be found. When woke up the next day, she had no eyesight and difficulty breathing. She was transferred to the emergency room in another university hospital and received care such as hemodialysis. She was diagnosed with binocular optic neuritis from an eye examination on Jan 16, 2016, She checked symptoms and urinary MeOH concentration for biological monitoring and was judged to be blindness finally from the physician of the Department of Occupational and Environmental Medicine on Jan. 22, 2016 [ 19 ]. Clear diagnosis from the outbreaks of symptoms took 7 days in Worker 1 case. Worker 2, worked for 4 months and 20 days on Sep. 02, 2015-Jan. 22, 2016. He couldn’t see after the end of work. He went to the hospital but the cause for the symptoms could not be found. Then he went to another second hospital with an ophthalmologist and underwent various tests but the cause for the symptoms also could not be found. After that the same day, the third consulting the other hospital he was diagnosed with MeOH poisoning by the physician of the Department of Occupational and Environmental Medicine on Jan. 22, 2016. Symptoms of the two workers (Worker 1 and 2) showed blindness, decreased consciousness, and vomiting. Exposed MeOH concentration in the workroom air was 1103 to 2220 ppm. Biological monitoring tests were accomplished on only 1 worker (Worker 1; Women). She had 7.632 mg/L in urinary MeOH and 31.320 mg/g cre. in urinary aluminum after 72 hours from work shift [ 19 ]. Table 4 Exposure status of workers to MeOH intoxication in aluminum CNC cutting process of Korean experience[ 3 , 18 , 19 ] Worker 1 a Worker 2 Sex Women Man Employment condition Illegally dispatched workers Illegally dispatched workers Affiliated Company Third-tier subcontractor Third-tier subcontractor Age 27 27 MeOH in workroom air (mg/l) 1661.5 as median (1103–2220) Exposure period for symptoms 119 days (3 Months 27 Days) 142days (4 Months 20 Days) Symptoms from exposure Vomiting Difficulty breathing Decreased consciousness Binocular optic neuritis Blindness Vomiting Decreased consciousness Visual dimness Blindness TLV-TWA of MeOH in South Korea is 200 ppm and STEL is 250 ppm. a 72 hours later after work-shift, urinary MeOH was 7.632 mg/L and 31.320 mg/g urinary creatinine. All workers had 12 hours work a day and shiftwork and exposed to 99.9% extra-pure grade MeOH. This study did not confirm whether long-term exposure (for example, continuous exposure by work for more than a year) caused symptoms that did not appear in low-concentration exposure due to the short exposure period of study participants. In addition, the subject of methanol vapor exposure was limited to humans (workers), and the simple dose-response relationship between exposure concentration and symptoms was confirmed. Most of the research data collected in this process were related to chronic exposure, and short-term exposure was used for volunteers. Indeed, the accident of exposure to methanol vapor by Korean workers was sub-chronic. To date, the relationship between the exposure period and the concentration of exposed steam has not been sufficiently explained in this study. In the future, clearer research on these focuses should be conducted. Conclusion The study estimated the methanol concentration to cause neurological intoxication from respiratory exposure in workers based on the dose-response relationship. Exposure of MeOH in the general population was estimated that not more than 2.0 mg/L of urinary MeOH from general environmental exposure of MeOH. Respiratory methanol concentration in 93 ppm to 200 ppm (TLV-TWA of ACGIH) did not show clear symptoms. Their corresponding urinary MeOH showed 22 to 42 ppm which was thought to be a linear relationship. Exposure of 459 ppm showed the symptom of dimmed vision which was thought the lowest concentration indicating optic nerve disorder. In the 1025.0 ppm, optic nerve disorders and central nerve disorders occurred. For the assistance to that exposure concentration, the epidemiological research for Korean MeOH occupational exposure accidents had played a pivotal role in proving symptom occurrence. Declarations Ethics approval and consent to participate Not applicable. Consent for publication Not applicable. Availability of data and material Not applicable. Competing interests Not Applicable (a single author) Funding The author declares that no funds, grants, or other support were received during the preparation of this manuscript. Authors' contributions Not applicable. Acknowledgements Not applicable. Authors' information (optional) Not applicable. References Givens M, Kalbfleisch K, Bryson S. Comparison of methanol exposure routes reported to Texas poison control centers. West J Emerg Med. 2008;9:150–3. Kavet R, Nauss KM. The toxicity of inhaled methanol vapors. Crit Rev Toxicol. 1990;21:21–50. Ryu J, Lim KH, Ryu DR, Lee HW, Yun JY, Kim SW, et al. Two cases of methyl alcohol intoxication by sub-chronic inhalation and dermal exposure during aluminum CNC cutting in a small-sized subcontracted factory. Ann Occup Environ Med. 2016;28:65. 10.1186/s40557-016-0153-9 . IPCS WHO. Environmental Health Criteria 196–Methanol1997. Kostic MA, Dart RC. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3407340","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Short Report","associatedPublications":[],"authors":[{"id":237702755,"identity":"3ddaf776-99ec-43b3-954d-03d0e78a2248","order_by":0,"name":"Chan-Seok Moon","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAr0lEQVRIiWNgGAWjYPACGxgjgWgtaaRrOUyCFv7+04kPPu44L29wu4Hxww+GtHyCWiRu5G42nHnmtuGGOweYJXsYciwbCGkxkODdJs3bdjvB4EYCgzQDQ4UBQVsM+M+CtJwDaWH+TZwWhlyQlgMgLWxAW3IIa4H4pS3ZcOadg22WPQZphLXw95/d+OBjm5083+3mwzd+VCQT1oJkH2MDyJ2kAAmSVI+CUTAKRsFIAgDKFDji1xkn+QAAAABJRU5ErkJggg==","orcid":"","institution":"Catholic University of Pusan","correspondingAuthor":true,"prefix":"","firstName":"Chan-Seok","middleName":"","lastName":"Moon","suffix":""}],"badges":[],"createdAt":"2023-10-03 10:29:29","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3407340/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3407340/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":45070387,"identity":"853711de-58bf-463a-859a-e44027524eca","added_by":"auto","created_at":"2023-10-23 08:37:41","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":349132,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3407340/v1/fdcdced5-c238-420e-bac5-43d4fdb9f3fc.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Exposure of High Concentration of Methanol Vapor for Neurological Intoxication in Factory Workers","fulltext":[{"header":"Background","content":"\u003cp\u003eIn fact, methanol (MeOH) is an extraordinarily toxic substance to the nervous system beyond imagination. However, the toxicity of MeOH is not well known except for the classical and general hazard information that can lead to blindness if drunk. Furthermore, little information has been known so far about toxicity through inhalation exposure to MeOH vapor [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. The MeOH can be easily absorbed from the exposure route of respiration and skin [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. The two exposure routes of MeOH are important to the workers who are using MeOH in the workshop [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. To respiratory monitoring, Pulmonary MeOH exposure is known that approximately 56\u0026ndash;82% of the total respiratory intake at the end of a work shift.\u003c/p\u003e \u003cp\u003eBiological monitoring from exposure indices such as human blood and urine can be monitored for MeOH exposure from the environment. Of the total exposed MeOH in workers, elimination was known via exhaling or urination for approx. 10% of unmetabolized MeOH. Absorption in the body is 70\u0026ndash;80% of the MeOH then is metabolized as formaldehyde through alcohol dehydrogenase and then transformed into free radicals and formic acid in the liver and red blood cells, resulting in the final products of carbon dioxide and water through formyl tetrahydrofolate synthetase [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eMeOH toxicity has symptoms of the central nervous system, metabolic acidosis, vision loss, and gastrointestinal symptoms which are caused by the metabolites from MeOH exposure [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. The metabolic acidosis level was related to the severity of the toxicity of MeOH. Namely, formic acid from the acidosis of formate from MeOH might cause ocular damage as acute poisoning [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. If MeOH is simultaneously exposed to other chemicals such as ethanol [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e], isopropanol [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e], or methyl ethyl ketone [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e], it is possible to show a positive or negative effect on the MeOH poisoning [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eMany useful studies about biological monitoring for MeOH exposure were thought to be reported until 2000 year. After that until current, the study for MeOH exposure as biological monitoring has not been fully studied. MeOH intoxication has been very high, although the chemical structure was very simple, and has not well known the chemical toxicities until the chemical accident in Korean manufacturing companies of smartphone parts. These companies were manufacturing smartphone side buttons and panels through an aluminum CNC (Computerized Numerical Control) cutting process.\u003c/p\u003e \u003cp\u003eRecent reports for MeOH exposure were usually approached to focus on an epidemiological and medical study of the Korean accident of CNC process and inhalational accident from misuse during the COVID-19 pandemic [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan additionalcitationids=\"CR15 CR16\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. However, reports have been very rare about exposure dose and responses for biological indices or neurological symptoms for the toxicities. Therefore, the study tried to dose-response relation with background concentration level, near 200 ppm of TLV-TWA of ACGIH, over 1000 ppm of MeOH as exposure dose, and their representative symptoms of MeOH as the response.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eResearch reports of MeOH exposure published in Google Scholar (including Korean reports) and PubMed from 1980 to 2023 present were examined. To investigate MeOH exposure, the clinical symptoms, and biological monitoring data, exposure status, and symptoms for representative methanol exposure were identified in searches using the keywords \u0026lsquo;methanol\u0026rsquo; and \u0026lsquo;exposure\u0026rsquo;. Among the papers, 40 papers from Google Scholar (from SCI-grade medical science journals) and PubMed were available articles for this study after review. All references included reports from international and domestic authorized public institutions. From the published reports, at first, the human (workers or volunteer) MeOH exposure concentration was identified and collected with exposure status such as co-exposed chemicals, exposure period, symptoms, biological indices data as urinary MeOH concentration, and subject general information as gender, age, MeOH working period if possible. Special attention was paid to the recent MeOH vapor exposure accident in South Korea because that had comparatively clearer information for clinical symptoms from MeOH vapor exposure concentration, exposure status, and symptoms for representative MeOH exposure [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e].\u003c/p\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eExposure sources and biological indices in the general population at the background level of MeOH\u003c/h2\u003e \u003cp\u003eThe general population has a low-level exposure to MeOH through the dietary intake of vegetables, fruits, beverages, and local traditional liquors [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan additionalcitationids=\"CR21\" citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Vegetable juice has 12\u0026ndash;640 mg/L of MeOH, and fruits have about 140 mg/L. Fermented beverages have 1,500 mg/L or more. Alcoholic beverages such as local traditional liquor, Korean wine, whiskey, and vodka contain a considerable amount of MeOH [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. As respirational exposure, smoking a cigarette is about 180 \u0026micro;g MeOH as vapor phase. Aspartame as an artificial sweetener is converted into MeOH about 10% when hydrolyzed in the human body [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Biological indices, in the Japanese population had that the urinary MeOH is in most cases less than 2 mg/L on the background exposure monitoring survey. The Urinary MeOH concentration was reported as 0.73 mg/L, 1.1 mg/L, 1.34 mg/L, 1.7 mg/L of GM. [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan additionalcitationids=\"CR25 CR26\" citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. In the Brazilian survey, urinary MeOH was 2.1 mg/L of GM [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eExposure of MeOH vapor below 200 ppm of TLV-TWA and symptoms\u003c/h2\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e shows the MeOH concentration of respiratory air and exposure status including urinary concentrations, subjects, exposure term, co-exposure chemical, and symptoms. Respiratory MeOH was available from 93 ppm to 200 ppm. And their corresponding urinary MeOH showed 22 to 42 ppm. MeOH from ambient air and urinary concentration of MeOH was thought to be a linear relationship [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Subjects were both workers and volunteers for exposure study of low-level MeOH. The exposure status of MeOH was constituted to exposure single chemical as MeOH which was not affected by other influential solvents like ethanol [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e], isopropanol [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e], methyl ethyl ketone [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Almost all workers had chronic exposure to MeOH. A symptom of MeOH exposure was a subclinical reaction of nasal respiratory mucosa [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eExposure of MeOH vapor below the 200 ppm and exposure status and symptoms\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRespiratory MeOH (mg/L)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUrinary MeOH (mg/L)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSubjects\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eExposure term\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eCo-exposure\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eSymptoms\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eRemarks\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e93\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eworkers\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eChronic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003esingle\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e107\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eworkers\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eno\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e120\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eworkers\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eChronic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003esingle\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e152\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eworkers\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eChronic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003esingle\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e[\u003cspan 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align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003evolunteer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAcute\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003esingle\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eno\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e200\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eworkers\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eChronic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003esingle\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e200\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eworkers\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eChronic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003esingle\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e200\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003evolunteer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAcute\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003esingle\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eno\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e[\u003cspan additionalcitationids=\"CR39\" citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e200\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003evolunteer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAcute\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003esingle\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eSubclinical reaction of nasal respiratory mucosa\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eExposure to MeOH of respiratory air over 200 ppm and symptoms\u003c/h2\u003e \u003cp\u003eIn Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, the concentration of methanol vapor could be confirmed at 249 ppm to 459 ppm. A total of three papers were confirmed in workplace workers using methanol, and in these cases, the symptoms were caused by chronic exposure. These reports targeted methanol vapor with single substance exposure, not mixtures. Exposure to 200 ppm level in the respiratory air (in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e), there was no symptom or showed to subclinical reaction of natural respiratory mucosa. Following 249 ppm exposure in the study volunteers showed weak fatigue [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. At 287.5 ppm of median (200\u0026ndash;375 ppm), recurrent headaches were shown [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. Exposure to 459 ppm reported \u0026lsquo;dimmed vision\u0026rsquo; and \u0026lsquo;nasal irritation\u0026rsquo; [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. In the case of this concentration, it was the lowest concentration indicating optic nerve disorder among the reports that were confirmed to date.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMeOH exposure level and status from ambient air and neurological symptoms\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eAmbient air (ppm)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSubjects\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eExposure term\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eCo-\u003c/p\u003e \u003cp\u003eexposure\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eSymptoms\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eRemarks\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e249.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003evolunteer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAcute\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003esingle\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eweak fatigue\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e287.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eworkers\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eChronic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003esingle\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003erecurrent headaches\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e459.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eworkers\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eChronic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003esingle\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003edimmed vision, nasal irritation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e \u003cp\u003e*; median for 200\u0026ndash;375 ppm.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eExposure of MeOH over 1000 ppm in respiratory air and symptoms\u003c/h2\u003e \u003cp\u003eIn Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e, typical central nervous system disorders and optic nerve disorders of MeOH exposure were identified at concentrations of 1000 ppm or higher. The atmospheric concentration in which optic nerve disorders and central nerve disorders clearly occur was reported as 1025.0 ppm. At that exposure level, blurred vision, and eye irritation, which appear to be optic nerve disorders, were identified. The exposure sources were ink components of the spirit duplicator, and mixed organic solvents such as ethanol or isopropyl alcohol were exposed in addition to methanol [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMeOH exposure level and status from ambient air and neurological symptoms\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eAmbient air (ppm)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSubjects\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eExposure term\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eCo-exposure\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eSymptoms\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eRemarks\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1025.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eworkers\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eChronic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003emixture\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eblurred vision, eye irritation, headache, dizziness, and nausea\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1625.3* (1030.1-2220.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eworkers\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSub-chronic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003esingle\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eamblyopia, binocular optic neuritis, visual dimness, blindness, vomiting, difficulty breathing, loss of pupillary reflex, metabolic encephalopathy, vomiting and decreased consciousness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1707.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eworkers\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eChronic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003esingle\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eheadaches, dizziness and eye irritation, blurred vision, and nausea/upset stomach\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1722.5*\u003c/p\u003e \u003cp\u003e(365\u0026ndash;3080)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eworkers\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eChronic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003esingle\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eblurred vision, Headache, Dizziness, Nausea\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6636.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eworkers\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAcute\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003emixture\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003edepression, nausea, vomiting, shortness of breath, photophobia decreased visual acuity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e8300\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eTemporary blindness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e \u003cp\u003e*; as median\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eExposure with a median of 1625.3 ppm of exposure level (1030.1-2220.5 ppm range) mostly showed typical symptoms of methanol exposure. The exposure occurred in the CNC cutting process which was one of the works of lathe with computerized numerical control for high precision work. The smartphone panel and its buttons were made by the CNC cutting process from aluminum material. During the process, MeOH is sprayed on the cutting side as a surface emulsifier. At that time, spread MeOH was evaporated inside the workshop. When the manufacturing of the smartphone side button is completed, the MeOH on the surface of the side button is removed using a high-pressure air blower (Korean usually called an air gun), which also evaporates a large amount of MeOH into the atmosphere of the workplace. These companies had not completely operated a ventilation system with the third subcontractor of a large electronics company in Korea which was not sufficiently controlled by Korean law [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. In the exposure concentration, most of the symptoms related to optic nerve disorders and central nervous system disorders were reported. It was very precisely evaluated to exposure accidents of hazardous chemicals in the workshop of Korea because exposure accidents of chemicals in respiratory air usually had difficulty in identifying their exposure level. The accident was that the use of ethanol was recommended in the CNC device usage manual, but it was caused by arbitrarily changing this ethanol to methanol. Since these accidents occurred at workplaces using a single methanol substance, a close epidemiological investigation was conducted by the Korean Ministry of Labor, and based on this, the exposure concentration of the indoor working environment was confirmed. All methanol-using workers report that it was caused by sub-chronic exposure [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Similar to this report, the disorder was shown by chronic exposure to a single methanol substance reported by IPCS [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. In the case of median 1722.5 ppm vapor exposure, workers' chronic exposure to single methanol showed no difference from the symptoms in the 1707.5 ppm concentration range at 1025.0 ppm reported earlier [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. As the highest concentration according to these symptoms identified in the report, the highest concentration in exposure accidents in Korea was 2220.5 ppm [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. In a study reported by Frederick et al., it was 3080 ppm [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. Frenia and Schauben reported 6636.6 ppm methanol exposure which is acute and is a case of mixture exposure caused by intentional inhalation of CARB-MEDIC carburetor container toluene (43.8%), methanol (23.2%), methyl, and propane (12%) [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. Temporary blindness was reported due to the exposure concentration in the atmosphere of 8300 ppm [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. However, symptoms of blindness were also reported at 1625.3 ppm previously, so it could occur even at low concentrations of 8300 ppm or less.\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eVapor exposure of 459 ppm concentration (Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e) showed dimmed vision and nasal irritation by Kawai et al. [\u003cspan class=\"CitationRef\"\u003e26\u003c/span\u003e]. In the case of this concentration, it was estimated carefully the lowest concentration indicated optic nerve disorder among the previous reports. The subject was mainly workers who use MeOH in their workshop and were exposed chronically to MeOH vapor as single chemical, not a solvent mixture. This exposure concentration was important because of adjacent to 200 ppm of TLV-TWA and 250 ppm of STEL by ACGIH. The exposure concentration 459 ppm was near the TLV-TWA and STEL which was 2.3 folds higher than the TLV-TWA and 1.8 folds higher than the STEL. Then, blurred vision and eye irritation related to optic nerve disorder were identified at 1025 ppm of Table \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e. About the concentration range of 459 to 1025 ppm, the author, unfortunately, couldn\u0026rsquo;t identify reports of methanol exposure worker and their symptoms. Vapor exposure range of 1025 ppm to 1755.5 ppm had clearly occurred the MeOH symptoms of optic nerve disorders and central nerve disorders. For the assistance to this exposure range, the exposure concentration of 1625.3 ppm could play a pivotal role in proving symptom occurrence. These 1625. 3 ppm exposure had a range of 1030.1 to 2220.5 ppm. And symptoms showed amblyopia, binocular optic neuritis, visual dimness, blindness, vomiting, difficulty breathing, loss of pupillary reflex, metabolic encephalopathy, vomiting, and decreased consciousness. These were involved in almost representative MeOH exposure symptoms. At that focus, these Korean reports had somewhat more special findings than previous reports. 1025 ppm had very close to 1030.1 ppm (in minimum exposure concentration of 1625.3 ppm) of the median of Korean MeOH accident reports[\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e19\u003c/span\u003e]. And 1707.5 ppm MeOH exposure report[\u003cspan class=\"CitationRef\"\u003e4\u003c/span\u003e] was very near to 1625.3 ppm and was thought to be a reference value to assist the Korean MeOH accident report. 1722.5 ppm had 365\u0026ndash;3080 ppm of wide exposure concentration range[\u003cspan class=\"CitationRef\"\u003e32\u003c/span\u003e]. The symptoms of the exposure concentration (1722.5 ppm) were also related symptoms with the Korean MeOH accident report.\u003c/p\u003e\n\u003cp\u003eFor a more precise exposure condition, the working records of the two workers were identified. The two workers in Table \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e had mainly worked overtime for 12 hours of working at the companies and were exposed to 99.9% of extra-pure grade MeOH [\u003cspan class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e19\u003c/span\u003e]. The two workers were formally reported by the Ministry of Employment of Labor in Korea that their neurological symptom was from MeOH vapor exposure at the workplace. Worker 1, worked for 3 months and 17 days from Sep. 21, 2015, to Jan 16, 2016. She showed vomiting before to shiftwork at 21 pm on Jan. 15, 2016, then went to the hospital for consulting and had blood tests. However, the cause for the symptoms could not be found. When woke up the next day, she had no eyesight and difficulty breathing. She was transferred to the emergency room in another university hospital and received care such as hemodialysis. She was diagnosed with binocular optic neuritis from an eye examination on Jan 16, 2016, She checked symptoms and urinary MeOH concentration for biological monitoring and was judged to be blindness finally from the physician of the Department of Occupational and Environmental Medicine on Jan. 22, 2016 [\u003cspan class=\"CitationRef\"\u003e19\u003c/span\u003e]. Clear diagnosis from the outbreaks of symptoms took 7 days in Worker 1 case. Worker 2, worked for 4 months and 20 days on Sep. 02, 2015-Jan. 22, 2016. He couldn\u0026rsquo;t see after the end of work. He went to the hospital but the cause for the symptoms could not be found. Then he went to another second hospital with an ophthalmologist and underwent various tests but the cause for the symptoms also could not be found. After that the same day, the third consulting the other hospital he was diagnosed with MeOH poisoning by the physician of the Department of Occupational and Environmental Medicine on Jan. 22, 2016. Symptoms of the two workers (Worker 1 and 2) showed blindness, decreased consciousness, and vomiting. Exposed MeOH concentration in the workroom air was 1103 to 2220 ppm. Biological monitoring tests were accomplished on only 1 worker (Worker 1; Women). She had 7.632 mg/L in urinary MeOH and 31.320 mg/g cre. in urinary aluminum after 72 hours from work shift [\u003cspan class=\"CitationRef\"\u003e19\u003c/span\u003e].\u0026nbsp;\u003c/p\u003e\n\u003ctable id=\"Tab4\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eExposure status of workers to MeOH intoxication in aluminum CNC cutting process of Korean experience[\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eWorker 1\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eWorker 2\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSex\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWomen\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMan\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEmployment condition\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIllegally dispatched workers\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIllegally dispatched workers\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAffiliated Company\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eThird-tier subcontractor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eThird-tier subcontractor\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAge\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e27\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMeOH in workroom air (mg/l)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e1661.5 as median\u003c/p\u003e\n \u003cp\u003e(1103\u0026ndash;2220)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eExposure period for symptoms\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e119 days\u003c/p\u003e\n \u003cp\u003e(3 Months 27 Days)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e142days\u003c/p\u003e\n \u003cp\u003e(4 Months 20 Days)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSymptoms from exposure\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eVomiting\u003c/p\u003e\n \u003cp\u003eDifficulty breathing\u003c/p\u003e\n \u003cp\u003eDecreased consciousness\u003c/p\u003e\n \u003cp\u003eBinocular optic neuritis\u003c/p\u003e\n \u003cp\u003eBlindness\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eVomiting\u003c/p\u003e\n \u003cp\u003eDecreased consciousness\u003c/p\u003e\n \u003cp\u003eVisual dimness\u003c/p\u003e\n \u003cp\u003eBlindness\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003eTLV-TWA of MeOH in South Korea is 200 ppm and STEL is 250 ppm.\u003c/p\u003e\n \u003cp\u003e\u003csup\u003ea\u003c/sup\u003e 72 hours later after work-shift, urinary MeOH was 7.632 mg/L and 31.320 mg/g urinary creatinine.\u003c/p\u003e\n \u003cp\u003eAll workers had 12 hours work a day and shiftwork and exposed to 99.9% extra-pure grade MeOH.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cdiv class=\"gridtable\"\u003e\u003cbr\u003e\u003c/div\u003e\n\u003cp\u003eThis study did not confirm whether long-term exposure (for example, continuous exposure by work for more than a year) caused symptoms that did not appear in low-concentration exposure due to the short exposure period of study participants. In addition, the subject of methanol vapor exposure was limited to humans (workers), and the simple dose-response relationship between exposure concentration and symptoms was confirmed. Most of the research data collected in this process were related to chronic exposure, and short-term exposure was used for volunteers. Indeed, the accident of exposure to methanol vapor by Korean workers was sub-chronic. To date, the relationship between the exposure period and the concentration of exposed steam has not been sufficiently explained in this study. In the future, clearer research on these focuses should be conducted.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe study estimated the methanol concentration to cause neurological intoxication from respiratory exposure in workers based on the dose-response relationship. Exposure of MeOH in the general population was estimated that not more than 2.0 mg/L of urinary MeOH from general environmental exposure of MeOH. Respiratory methanol concentration in 93 ppm to 200 ppm (TLV-TWA of ACGIH) did not show clear symptoms. Their corresponding urinary MeOH showed 22 to 42 ppm which was thought to be a linear relationship. Exposure of 459 ppm showed the symptom of dimmed vision which was thought the lowest concentration indicating optic nerve disorder. In the 1025.0 ppm, optic nerve disorders and central nerve disorders occurred. For the assistance to that exposure concentration, the epidemiological research for Korean MeOH occupational exposure accidents had played a pivotal role in proving symptom occurrence.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and material\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot Applicable (a single author)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eThe author declares that no funds, grants, or other support were received during the preparation of this manuscript.\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; information (optional)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eGivens M, Kalbfleisch K, Bryson S. 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Toxicol Sci. 2005;88:30\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"methanol, vapor, exposure, inhalation, symptoms","lastPublishedDoi":"10.21203/rs.3.rs-3407340/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3407340/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eA few studies of biological monitoring of MeOH vapor exposure focused on human subjects were thought to have been reported until 2000. After that until current, the study of MeOH vapor exposure concentration and neurological toxicity as the dose-response relationship for biological monitoring has not been fully studied.\u003c/p\u003e\u003ch2\u003eObjective\u003c/h2\u003e \u003cp\u003eThe study aims to reasonable estimate the step-by-step methanol concentration of neurological toxicity from respiratory exposure in workers.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThe methanol exposure was constituted to focus on respiratory air and symptoms. The previous reports were searched for dose-response relation between methanol vapor concentration and urinary methanol concentration and between methanol vapor concentration and symptoms for representative methanol exposure. Google Scholar (including Korean reports) and PubMed from 1980 to 2023 present were examined as search engines.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eRespiratory methanol exposure 93 ppm to 200 ppm of vapor concentration (TLV-TWA of ACGIH) did not show clear symptoms. And their corresponding urinary methanol showed 22 to 42 ppm. Exposure to 459 ppm of vapor was reported to be the symptom of dimmed vision which was the lowest concentration indicating optic nerve disorder. In the 1025.0 ppm of vapor, optic nerve disorders and central nerve disorders occurred.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eRespiratory methanol exposure had initiated clinical symptoms as optic nerve toxicity from 459.0 ppm at the vapor phase. In the 1025.0 ppm of vapor, representative symptoms were identified such as optic nerve, and central nerve disorders.\u003c/p\u003e","manuscriptTitle":"Exposure of High Concentration of Methanol Vapor for Neurological Intoxication in Factory Workers","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2023-10-09 09:54:06","doi":"10.21203/rs.3.rs-3407340/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"f3276cd8-2ee9-4e9e-8e12-13cc908814b6","owner":[],"postedDate":"October 9th, 2023","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2023-10-23T08:29:34+00:00","versionOfRecord":[],"versionCreatedAt":"2023-10-09 09:54:06","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3407340","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3407340","identity":"rs-3407340","version":["v1"]},"buildId":"_2-kVJe1T_tPrBINL-cwx","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}