1. Acute chemical intoxications – systemically toxic chemicals Paide 4.11.03 Tiina Santonen

2. TYÖTERVEYSLAITOS Chemical asphyxiants –Carbon monoxide –Cyanides –Hydrogen sulphide –Methaemoglobinemia –inducing substances Anticholinesterase inhibitors Organic solvents

3. TYÖTERVEYSLAITOS Carbon monoxide the most common cause of chemical intoxication in industry mechanism of action: binds to haemoglobin at 200-300 higher affinity than oxygen and forms carboxyhaemoglobin, but it also enters the tissues and attacts the cytochrome system

4. TYÖTERVEYSLAITOS Adapted from Rom W.N.: Environmental and Occupational Medicine, 3rd ed., Philadelphia, 1998.

5. TYÖTERVEYSLAITOS smoking causes 3-8 % COHb Finnish OEL 30 ppm => 4 % COHb IDLH 1200 ppm /30 min

6. TYÖTERVEYSLAITOS The amount of carboxyhaemoglobin is highly dependent on the physical activity of the exposed individual % COHb=[CO]air x K x T K=constant for physical activity, at rest K=0.018, in light work K=0.048 If the air concentration of CO is 1% (=10000 ppm), 50% COHb level will be reached at rest in 16 min, in light work in 6 min

7. TYÖTERVEYSLAITOS Individual susceptibility: people suffering from heart and lung diseases at highest risk Pregnancy! methylene chloride forms carbon monoxide in the body

8. TYÖTERVEYSLAITOS Carbon monoxide poisoning - treatment diagnosis: anamnesis, status, blood carboxyhaemoglobin content (does not necessary correlate with the severity of symptoms!) monitoring of ECG, electrolytes and arterial blood gases treatment: 100 % oxygen hyperbaric oxygen ( in special cases)

9. TYÖTERVEYSLAITOS Hydrogen cyanide and Cyanide salts Cyanides are used e.g. in the metal finishing operations, HCN is formed also in fires Cyanide ion (CN - ) inhibits the cellular respiration by binding to mitochondrial cytochrome oxidases affects all organs, however, the organs with high oxygen demand most susceptible

10. TYÖTERVEYSLAITOS Hydrogen cyanide: bitter almond-like odor Finnish OEL 10 ppm / 15 min IDLH for hydrogen cyanide 50 ppm / 30 min symptoms of cyanide poisoning are due to the decreased tissue oxygen utilisation and became evident mainly as CNS symptoms like weakness, dizziness, nausea, headache, confusion, convulsions and unconsciousness

11. TYÖTERVEYSLAITOS Note: cyanide salts like KCl, NaCl, Ca(CN)2 are well absorbed through the skin Treatment of cyanide poisoning: –First aid: administration of 100 % oxygen, amyl nitrite inhalation –Hydroxycobalamin 5 g i.v. during the 30 minutes –(sodium nitrite or 4-dimethylaminophenol [4- DMAP]) –sodium tiosulfate 25% 50 ml –(dicobalt edetate in severe cases) Education of the workers for safe handling!

12. TYÖTERVEYSLAITOS Nitriles Nitriles like acrylonitrile deliberate cyanide in the body acrylonitrile is used e.g. in the manufacture of acrylic fibers, ABS- plastics, latexes and nitrile rubber acrylonitrile IDLH 85 ppm, well absorbed through the skin, high vapour pressure symptoms of poisoning are equivalent to those of cyanides treatment of poisoning is equivalent to that of cyanide poisoning

13. TYÖTERVEYSLAITOS Hydrogen sulfide formed during the decomposition of organic materials; exposure to H 2 S may occur e.g. in sewage treatment plants, cellulose industry) odor of rotten eggs at low concentrations (odor threshold 0.008 ppm), however, at high concentrations the sense of smell is paralyzed

14. TYÖTERVEYSLAITOS highly toxic, inhibits cellular respiration like cyanide Finnish OEL 10 ppm / 15 min IDLH 100 ppm /30 min symptoms of poisoning resemble those of cyanide poisoning treatment:100 % oxygen (amyl nitrite, sodium nitrite, 4-DMAP)

15. TYÖTERVEYSLAITOS Methaemoglobinemia – inducing agents methaemoglobinemia = oxidation of haemoglobin Fe2+ to Fe3+ => inability of haemoglobin to carry oxygen many aromatic amino and nitro compounds (e.g. aniline, nitrobenzenes), and nitrites and nitric oxide may induce methaemoglobinemia

16. TYÖTERVEYSLAITOS Physical properties of the compound determine the possible routes of exposure –For example sodium and potassium nitrites are solid compounds, which do not evaporise at normal conditions, but amyl and isobutylnitrites are liquids with a vapour pressure and may evaporise. Aniline and nitrobenzenes are liquids which may evaporate and be absorbed through the skin (good fat-solubility)

17. TYÖTERVEYSLAITOS Symptoms of methaemoglobinemia: –cyanosis (15-25 % methamoglobin), more severe cyanosis and CNS symptoms at 40 % level of methaemoglobinemia treatment of methaemoglobinemia: –100 % oxygen –Monitoring of the methaemoglobin levels –1-2 mg/kg 1 % methylene blue i.v. in severe poisoning cases (usually caused by ingestion)

18. TYÖTERVEYSLAITOS Anticholinesterase inhibitors -organophosphorus pesticides and nerve agents like sarin and tabun

19. TYÖTERVEYSLAITOS Organophosphorus pesticides e.g. azinphos-methyl, dichlorvos, dimethoate, fenitrothion, azamethiphos, isophenphos, chlorpyriphos used as insecticides depending on the use, the main route of exposure to organophosphates is the skin, but also inhalation exposure may occur

20. TYÖTERVEYSLAITOS Organophosphorus pesticides irreversible inactivation of acetylcholinesterase => increase in acetylcholine levels in nerve endings => Cholinergic symptoms which include salivation, sweeting, lachrymation, miosis, bradycardia, hypotension (muscarinic effects), muscle spasms, convulsions and finally paralysis (nicotinic effects)

21. TYÖTERVEYSLAITOS Organophosphorus pesticides treatment of poisoning: - the patient should be kept at rest -supportive care: oxygen, ventilation -treatment of convulsions with diazepam -antidote: atropine 2 mg every 5-10 min -obidoxime 250 mg i.v. reactivates acetylcholinesterase biological monitoring: measurement of blood acetylcholinesterase activity

22. TYÖTERVEYSLAITOS Organic solvents aliphatic and aromatic hydrocarbons, halogenated hydrocarbons, alcohols, ketones, ethers, esters toxicity varies generally may cause CNS depressant effects, some of them may sensitize cardiac muscle for catecholamines and cause arrhytmias Lipid solubility affects the toxicity Abusers!