Acute chemical intoxications - chemicals toxic to the respiratory system Vesa Riihimäki Unit for toxicological risk assessment Finnish Institute of Occupational Health TYÖTERVEYSLAITOS

Respiratory irritants and toxicants Gases and vapours - acetic acid/-anhydride - ammonia - formaldehyde - sulphur dioxide - chlorine - hydrogen chloride - hydrogen fluoride - nitrogen oxides - ozone - toluene diisocyanate TYÖTERVEYSLAITOS Aerosols - cadmium oxide - zinc chloride - "tear gases", e.g. CN - mustards Decomposition products and complex mixtures - fire gases and smokes Systemic lung toxicants - paraquat

TYÖTERVEYSLAITOS Toxicants contained in fire emissions Toxicant aldehydes organic acids hydrogen chloride hydrogen fluoride diisocyanates nitrogen oxides soot particles Source wood, cotton, petroleum wood, cotton, petroleum PVC plastic fluorinated resins, freons polyurethane products nitrocompounds, nitrates all fires

Exposures at workplace Human errors, machine failures and accidents TYÖTERVEYSLAITOS release of freon over hot cooking plates flame cutting of cadmium-plated metal structures welding with aluminium (TIG method) overflow of nitric acid resulting in contact with wood structures fire in a trichloroethylene degreasing bath hydrogen peroxide emissions from a malfunctioning aseptic packaging machine TDI emissions in polyurethane mattress production broken ammonia refrigeration system in a warehouse repairs and overhauls of processes containing reactive substances

Community exposure Operational error in a community swimming pool (release of chlorine gas) Leak in the refrigeration system of an ice hockey stadium (release of ammonia) Industrial accident Fire in a warehouse containing PVC material Traffic accident (chemical transports) Terrorist attack TYÖTERVEYSLAITOS

The respiratory system: - upper airways - lower airways - the lungs - particle size < 5 μm 5-10 μm > 10 μm - water solubility

Deposition of irritants in the respiratory system vs symptoms Location Upper airways: water soluble acetic acid, ammonia, formaldehyde Upper & lower airways: moderately water soluble chlorine, hydrogen chloride, sulphur dioxide Lower airways & lungs: sparsely water soluble acrolein, nitrogen oxides, ozone, phosgene, TDI TYÖTERVEYSLAITOS Symptoms Pain and mucous secretions from nose and throat, hoarse voice, difficulty swallowing Cough, pain & tightness of chest, wheezing Dry irritant cough, wheezing, blood-stained expectoration, dyspnoea

Mode/mechanism of action Cell membrane injury, e.g. protein denaturation due to crosslinking, oxidation and other reactions (immediate effect) Recruitment of neutrophils and macrophages with potential generation of reactive oxygen species (later effect) TYÖTERVEYSLAITOS

Determinants of respiratory injury Exposure concentration x duration (Haber's rule). Concentration has however more impact, e.g. chlorine. Toxic potency of compound Potency to cause lung oedema (ppm x min) Phosgene50 Chlorine1 000 Ammonia TYÖTERVEYSLAITOS

Principles of medical management Keep at rest in half upright position In breathing problems provide oxygen, CPAP as necessary Parenteral diazepam (10 mg) to restless patients Use beta2-sympathomimetic bronchodilators and steroids to alleviate bronchoconstriction Early intubation if laryngeal oedema is imminent In case of possible lung toxicity, keep the patient under observation for at least 24 hours and arrange for the availability of a respirator. TYÖTERVEYSLAITOS

Clinical manifestations following exposure to respiratory toxicants Upper airway irritation and mucous membrane injury, threat of laryngeal oedema Upper and lower airway irritation and mucous membrane injury, threat of bronchopneumonia Lower airway and lung injury, threat of lung oedema and protracted alveolitis/pneumonitis TYÖTERVEYSLAITOS

Patient recovery Prognosis is normally good Possible sequelae are - chronic bronchitis - reactive airways dysfunction syndrome (RADS) - bronchiectasis - bronchial stenosis - tracheobronchial polyps - bronchiolitis obliterans (rarely) - ARDS and lung fibrosis TYÖTERVEYSLAITOS

Implications for occupational health practice Does long-term exposure to respiratory irritants cause chronic toxicity? Is medical surveillance indicated? Depends on levels of exposure and individual susceptibility Examples - ozone (airway hyperresponsiveness & inflammation, structural changes of the lung) - sulphuric acid mists (laryngeal cancer) - welding (bronchitis, respiratory infections, lung cancer) TYÖTERVEYSLAITOS