Introduction to toxicity knowledge of methanol and acetonitrile_Kain Industrial Additives

【Diagnosis and Differential Diagnosis】
The diagnosis of acute acetonitrile poisoning is mainly based on a reliable history of large-dose exposure to acetonitrile and clinical characteristics. Similar symptoms in co-contacts are obviously suggestive; timely measurement of CN-, SCN- and acetonitrile content in plasma is suggestive, and is the biological hazard of acetonitrile exposure. Markers, but cannot indicate the presence or absence of poisoning and its extent.
Acute acetonitrile poisoning should be differentiated from poisoning by other industrial poisons that exist at the work site, such as organic solvents and asphyxiating gases, and should be differentiated from cerebrovascular accidents, diabetic coma, etc.

【Treatment】
The treatment of acute acetonitrile poisoning can be found in the hydrogen cyanide section, but the dose of methemoglobin-generating agent can be halved. When sodium thiosulfate is administered, a slow-acting methemoglobin-generating agent such as p-aminopropiophenone (PAPP) can be used early. One tablet is taken orally each time and can be reused every 4 hours. Only sodium thiosulfate is used the next day. Just maintain it; the dosage of sodium thiosulfate can be halved after 2 days, and discontinued after 3 to 5 days. Since acetonitrile itself still has toxic effects, when using cyanide antidote, symptomatic and supportive treatment should be actively carried out, attention should be paid to maintaining heart, lung, and brain functions, and reasonable fluid replenishment and diuresis to accelerate the excretion of poisons and reduce kidney damage.
                                                                         
Methanol
Methanol; Methyl alcohol; Carbinol; Wood alcohol; Wood spirit; Methyl hydroxide; CAS: 67-56-1 Physical and chemical properties: colorless, transparent, highly volatile, flammable liquid. Slightly alcoholic smell. Molecular formula C-H4-O. Molecular weight 32.04. Relative density 0.792 (20/4℃). Melting point -97.8℃. Boiling point 64.5℃. Flash point 12.22℃. Autoignition point is 463.89℃. Vapor density 1.11. Vapor pressure 13.33KPa (100mmHg 21.2℃). The lower explosion limit of steam and air mixture is 6~36.5%. Miscible with water, ethanol, ether, benzene, ketones, halogenated hydrocarbons and many other organic solvents. It is easy to catch fire when exposed to heat, open flame or oxidant. Will explode if exposed to fire.
Ways of Invasion
Mainly absorbed through the respiratory tract and gastrointestinal tract, and can also be partially absorbed through the skin.

【Introduction to Toxicology】
Human (male) oral LDL 6422mg/kg; TDL 3429mg/kg. Oral TDL for women is 4mg/kg. It has also been reported that human oral LDLo ranges from 428mg/kg to 143mg/kg; inhaled TCL ranges from 86000mg/m3 to 300ppm.

Rat oral LD50: 5628mg/kg; inhalation LC50: 64000ppm/4H. Mouse oral LD50: 7300mg/kg; inhaled LCL

And then oxidized to formic acid. This product is slowly oxidized in the body, only 1/7 of ethanol, and is excreted slowly, with obvious accumulation effect.

Methanol that has not been oxidized is excreted from the body through the respiratory tract and kidneys, and part of it is slowly excreted through the gastrointestinal tract. It is speculated that people inhale airMethanol concentration in the air is 39.3~65.5g/m^3, which can cause poisoning in 30~60 minutes. Oral administration of 5 to 10 ml can cause severe poisoning; oral administration of 15 ml at one time, or a total of 124 to 164 ml in divided doses within 2 days, can cause blindness. There are reports that oral administration of 30ml at one time can cause death. Methanol mainly acts on the nervous system, has obvious anesthetic effects, and can cause cerebral edema. The anesthetic concentration of methanol is close to LC, so it is more dangerous. It has a special selective effect on the optic nerve and retina, easily causing optic nerve atrophy and blindness. Methanol vapor has a strong irritating effect on respiratory mucosa. The toxicity of methanol is related to the accumulation of its metabolites formaldehyde and formic acid. It was previously believed that the toxic effects were mainly caused by formaldehyde. Formaldehyde can inhibit the oxidative phosphorylation process of the retina, preventing the synthesis of ATP in the membrane, causing cell degeneration, and finally causing optic nerve atrophy. Recent studies have shown that formaldehyde is quickly metabolized into formic acid, and metabolic acidosis and eye damage caused by acute poisoning are mainly related to the formic acid content. Methanol inhibits certain oxidase systems in the body, inhibits the aerobic decomposition of sugar, causes the accumulation of lactic acid and other organic acids and formic acid, and causes acidosis. It is generally believed that the toxicity of methanol is caused by itself and its metabolites. DLH: +6000 ppm [R28]

【Clinical manifestations】
The main damaged target organs after acute methanol poisoning are the central nervous system, optic nerve and retina. The incubation period of inhalation poisoning is generally 1 to 72 hours, and sometimes 96 hours;
Oral poisoning usually takes 8 to 36 hours; if ethanol is ingested at the same time, the incubation period is longer.

【Clinical Characteristics】
Irritation symptoms: Inhaling methanol vapor can cause eye and respiratory mucosa irritation symptoms. Central nervous system symptoms: Patients often experience dizziness, headache, dizziness, fatigue, staggering gait, insomnia, indifferent expression, and cloudy consciousness. In severe cases, confusion, coma, and epileptic convulsions may occur. People with severe oral poisoning may have symptoms of extrapyramidal damage or Parkinson’s syndrome. Head CT examination revealed symmetrical infarction and necrosis of the lentiform nucleus and central subcortical white matter. Symptoms such as hallucinations and depression. Eye symptoms: Initially, dark shadows in front of the eyes, flashing lights, blurred vision, eyeball pain, photophobia, diplopia, etc. In severe cases, vision drops sharply, which can lead to permanent blindness in both eyes. Examination shows that the pupils are enlarged or narrowed, the reaction to light is slow or disappears, papilledema, peripheral retinal congestion, hemorrhage, edema, and optic nerve atrophy in the late stage. Acidosis: The binding capacity of carbon dioxide is reduced, and in severe cases, cyanosis occurs, and breathing is deep and rapid, showing Kussmaul breathing.

Digestive system and other symptoms: Patients have nausea, vomiting, upper abdominal pain, etc., which may be complicated by liver damage. Oral poisoning may be complicated by acute pancreatitis. A few cases are accompanied by tachycardia, myocarditis, S-T segment and T wave changes, acute renal failure, etc. Severe acute methanol poisoning can cause severe headache, nausea, vomiting, sharp decline in vision, and even blindness, confusion, delirium, convulsions and coma. Eventually, death may occur due to respiratory failure. According to the history of methanol exposure, clinical manifestations mainly include central nervous system damage, eye damage and metabolic acidosis in a short period of time. Referring to the on-site hygiene investigation and excluding other diseases with similar manifestations, the diagnosis is not difficult after comprehensive analysis. If necessary, blood and urine methanol measurements can be made. In the early stage of poisoning, it should be distinguished from colds, neurasthenia, acute gastroenteritis, etc. In addition, it should be distinguished from methyl chloride, ethylene glycol acute poisoning and encephalopathy and optic nerve damage caused by other reasons. Detailed occupational history inquiries, on-site hygiene investigations, close observation of disease progression, and laboratory examinations are necessary to arrive at a correct diagnosis.

①Blood methanol>15.6mmol/L; or formic acid>4.34mmol/L;
②Severe metabolic acidosis;
③Severe visual impairment or papillretinal edema.

Antidote: Ethanol is the antidote for methanol poisoning. The application of ethanol can prevent the oxidation of methanol and promote the discharge of methanol. Use 10% glucose solution to prepare a 5% ethanol solution and infuse it slowly intravenously. There is not much clinical experience in China. Correct acidosis: Based on blood gas analysis or carbon dioxide binding capacity measurement and clinical manifestations, give sodium bicarbonate solution or sodium lactate solution as soon as possible. Supportive and symptomatic treatment: Actively prevent and treat cerebral edema according to the condition, reduce intracranial pressure, improve fundus blood circulation, and prevent optic neuropathy. Maintain respiratory and circulatory functions and maintain electrolyte balance. Give plenty of B vitamins. It has been suggested to use formate and 4-methylpyrazole (4MP) to treat methanol poisoning, which has been confirmed in experimental studies on monkeys but has not been used clinically so far.