Acute chemical intoxications –systemically toxic chemicals

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

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

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

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

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

8. 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. 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. 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. 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. 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. Hydrogen sulfide • formed during the decomposition of organic materials; exposure to H2S 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. 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. 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. 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. 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. Anticholinesterase inhibitors -organophosphorus pesticides and nerve agents like sarin and tabun

19. 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. 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. 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. 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!