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Chapter: Modern Medical Toxicology: Asphyxiant Poisons: Toxic Gases

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Formaldehyde - Respiratory Irritants Asphyxiant Poison

Dormol, fannoform, formalin, formalith, formic aldehyde, formol, lysoform, methanal, methyl aldehyde, methylene oxide, morbicid, oxomethane, oxymethylene.

Formaldehyde

Synonyms

·              Dormol, fannoform, formalin, formalith, formic aldehyde, formol, lysoform, methanal, methyl aldehyde, methylene oxide, morbicid, oxomethane, oxymethylene.

Physical Appearance

·      Colourless gas with strong pungent smell.

·      Formalin is an aqueous solution of formaldehyde containing 37 to 40% formaldehyde and 10 to 15% methanol.* This is however generally referred to as 100% formalin. Therefore 10% formalin would actually mean a 1: 10 dilution of such a commercial preparation and contains 3.7% formaldehyde. Formalin is a clear, colourless liquid with a pungent odour. Some formaldehyde aqueous solutions can be amber to dark brown or even reddish in colour.

·      Formaldehyde is also available as a solid polymer, para-formaldehyde, in a powder or flaked form containing from 90 to 93% formaldehyde, and as its cyclic trimer, trioxane.

Uses and Sources

·      Industrial/Household: Formaldehyde is used in fertilisers, pesticides, sewage treatment, paper-making, preservatives, embalming fluids, disinfectants, foam insulation, urea and melamine resins, artificial silk and cellulose esters, explo-sives, particle board, plywood, air fresheners, cosmetics, fingernail polishes, water-based paints, tanning and preserving hides, and as a chemical intermediate. It is also used as a preservative and coagulant in latex rubber, and in photograph developing processes and chrome printing.

·      Medical/Veterinary: Therapeutically, formaldehyde has been used to treat massive haemorrhagic cystitis and hydatid cysts of the liver. It has also been used in veterinary medicine. Formaldehyde is sometimes used to sterilise dialysis machines. Dialysis patients using dialyser machines sterilised with formaldehyde receive a small dose with each treatment. The most frequent sequelae is a type of autoim-mune haemolytic anaemia; rarely, peripheral eosinophilia may occur. Severe hypersensitivity reactions have been observed in a few of these dialysis patients, though the exact relationship of this to formaldehyde-sterilised equipment is unclear. Currently other sterilisers are in use such as a mixture of hydrogen peroxide and peracetic acid.

·              Formaldehyde is a common contaminant of smoke and is even present to a significant extent in tobacco smoke. Burning wood, cigarette smoking, and other forms of incomplete combustion emit formaldehyde. Addicts some-times dip cigarettes of tobacco or cannabis in formaldehyde (“amp” or “dank”) before smoking, in the belief that this produces a hallucinogenic effect and “body numbness”. It is a dangerous practice and can result in encephalopathy, pulmonary oedema, rhabdomyolysis and coma.

Mode of Action

Formaldehyde is a protoplasmic poison and potent caustic. It causes coagulation necrosis, protein precipitation, and tissue fixation. Due to conversion in the body to formic acid there is usually profound metabolic acidosis, and this is aggravated by the concomitant presence of methanol (a common additive in formalin solutions) which is also broken down to formic acid. Delayed absorption of methanol might occur following ingestion of formalin if the formaldehyde causes fixation of the stomach.

Clinical Features

Acute Poisoning:

·              Inhalation—cough, lacrimation, dyspnoea, chest pain, wheezing, rhinitis, anosmia, tracheitis, bronchitis, laryngospasm, pulmonary oedema, headache, weak-ness, dizziness, and palpitations.

·              Ingestion—severe abdominal pain, vomiting, diarrhoea, haematemesis, tachypnoea, hypotension, cyanosis, altered mental status, and coma. Seizures, jaundice, albuminuria, haematuria, anuria, and metabolic acidosis have also been reported. Ulceration of mouth, oesophagus, and stomach is common. Strictures and perforation are possible delayed complications. Renal failure is a frequent complication in severe poisoning. Hepatotoxicity has been reported. Skin and mucous membrane may appear whitened. If the patient survives for more than 48 hours, the prognosis is good.

·              Dermal exposure—dermatitis, brownish discolouration of the skin, urticaria, and pustulovesicular eruptions, may develop from dermal exposure. Concentrated solutions can cause coagulation necrosis.

·              Ocular exposure—irritation, lacrimation, and conjuncti-vitis may develop with exposure to vapours. Eye expo-sure to solutions with high formaldehyde concentrations may produce severe corneal opacification and loss of vision. Inhalation or ingestion of formaldehyde has not been found to affect vision in humans or animals.

 

Chronic Poisoning:

·              Formaldehyde is a known carcinogen in animals, and epidemiologic data among humans are mounting in implicating the chemical in human carcinogenesis. There are reports of increased incidence of nasopha-ryngeal cancers in individuals occupationally exposed to formaldehyde. Some epidemiologic studies have found a slightly elevated risk for lung cancer mortality with formaldehyde exposure. Suggestive association between occupational exposure to formaldehyde and deaths from breast cancer was seen in one case-control study.

·              Asthma and dermatitis in sensitive individuals.

·              Possible disturbances in memory, mood, and sleep; headache, and fatigue. Seizures may also be induced.

·              Occupational exposure at recommended limits is not thought to present a reproductive risk. Formaldehyde exposure among female hospital workers did not correlate with an increase in spontaneous abortion in one study, but did correlate in another.

·              Formaldehyde is a potent genotoxin and has been reported to be active in many short-term genetic tests, including the Ames Salmonella assay and other assays for mutation using bacteria, chromosome aberrations and sister chromatid exchanges in vitro and in vivo, and many assays detecting direct effects on DNA.

Usual Fatal Dose

·              About 30 to 50 ml of 100% formalin (liquid) ; more than 100 ppm (gas). Ingestion of as little as 30 ml of 37% (approximately 2 tablespoons) formaldehyde solution (formalin) has been reported to cause death in an adult. Exposure to air concen-trations as low as 2 ppm can cause eye and upper respiratory irritation. Dermal exposure to formalin can result in irritation (acute), or allergic dermatitis (chronic) in susceptible individ-uals. Exposure to solutions of 2 to 10% may result in blisters, fissures, and urticaria.

Diagnosis

·      Formaldehyde plasma levels are not widely available, but may help in dialysis monitoring.

·      Monitor acid base status in symptomatic patients.

·      Monitor liver function tests.

·      Monitor haematocrit and haemoglobin concentration in dialysis patients repeatedly exposed parenterally to formal-dehyde.

·      Monitor blood methanol levels after significant formalin ingestion.

·      Pulmonary function testing and nasal and bronchial provo-cation tests may be recommended in patients with signs and symptoms of reactive airways dysfunction following inhalation of formaldehyde.

·      The presence of a small amount of endogenously derived formate in human urine is normal; however, formate derived from the metabolism of formaldehyde, several other indus-trial compounds (methanol, halomethanes, acetone) and some pharmaceutical compounds may elevate the urine formate concentration above the normally expected values.

·      Urinary formic acid levels were shown to be subject to a great deal of individual variation and did not correlate with known exposures to formaldehyde. Formic acid is not a suitable biomarker for formaldehyde exposure.

Treatment

Acute Poisoning:

·              Dilution with milk or water as a first-aid measure may help reduce corrosive effects. Emesis is contraindicated. Activated charcoal may be of benefit.

·              Gentle gastric aspiration with a soft nasogastric tube (if the victim is seen within 1 hour of ingestion).

·              Sodium bicarbonate IV.

·              Haemodialysis.

·              Ethanol infusion will help counteract methanol toxicity.

·              Monitor electrolytes, fluids, acid-base, and renal func-tion.

·              Dopamine or noradrenaline for hypotension

·              Watch for signs of gastrointestinal haemorrhage and perforation.

·              Early endoscopy to assess the degree of injury.

·              Inhalation exposure: Administer 100% humidified supplemental oxygen, perform endotracheal intubation, and provide assisted ventilation as required. Administer inhaled beta adrenergic agonists if bronchospasm develops. Maintain adequate ventilation and oxygena-tion with frequent monitoring of arterial blood gases and/or pulse oximetry. If a high FIO2 is required to maintain adequate oxygenation, mechanical ventilation and positive-end-expiratory pressure (PEEP) may be required; ventilation with small tidal volumes (6 ml/ kg) is preferred if ARDS develops.

·              Exposed skin and eyes should be flushed with copious amounts of water. Patients with ocular exposure to significant concentrations of formaldehyde should be evaluated by an ophthalmologist.

Chronic Poisoning:

·              Removal of patient from exposure.

·              Symptomatic measures.

·              Preventive measures include exhaust ventilation at place of work, use of goggles, face shields, gloves, and aprons.

Autopsy Features

·              Odour of formalin around the mouth and nostrils, and in the stomach contents.

·              Inflammatory oedema of oesophagus, larynx, and lungs.

·              Stomach (and sometimes the proximal small intestine) may show signs of “fixation” of tissues. Histological details may be well preserved.

·              Kidneys may reveal microscopic evidence of tubular necrosis.

·              Autopsy Diagnosis: To confirm the presence of formalde-hyde in the gastric contents, a small quantity of the latter is dissolved in resorcinol in a test tube and sulfuric acid is gently poured along the sides of the tube. A red to violet coloured ring will develop at the junction of the two solu-tions.

Forensic Issues

·              Most reported cases of acute poisoning are either accidental or suicidal in nature. Chronic poisoning is invariably due to occupational exposure.

·              Some Indian studies conducted in embalming rooms of medical colleges revealed fairly high formaldehyde concentra-tion of ambient air, stressing the need for fixing standard limits of exposure in work places in India like in the West.

 

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