Acute chemical intoxications –Acute chemical intoxications –systemically toxic chemicalssystemically toxic chemicals

Paide 4.11.03 Tiina Santonen

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Chemical asphyxiants – Carbon monoxide– Cyanides– Hydrogen sulphide – Methaemoglobinemia –inducing

substancesAnticholinesterase inhibitors Organic solvents

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Carbon monoxideCarbon monoxidethe most common cause of chemical

intoxication in industrymechanism 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

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

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smoking causes 3-8 % COHb

Finnish OEL 30 ppm => 4 % COHb

IDLH 1200 ppm /30 min

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The amount of carboxyhaemoglobin is highly dependent on the physical activity of the exposed individual

% COHb=[CO]air x K x TK=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

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Individual susceptibility: people suffering from heart and lung diseases at highest risk

Pregnancy!

methylene chloride forms carbon monoxide in the body

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Carbon monoxide poisoning -Carbon monoxide poisoning -treatmenttreatment

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 % oxygenhyperbaric oxygen

(in special cases)

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Hydrogen cyanide and Hydrogen cyanide and Cyanide saltsCyanide 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

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Hydrogen cyanide: bitter almond-like odor

Finnish OEL 10 ppm / 15 minIDLH for hydrogen cyanide 50 ppm /

30 minsymptoms 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

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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!

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NitrilesNitriles 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

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Hydrogen sulfideHydrogen 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

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highly toxic, inhibits cellular respiration like cyanide

Finnish OEL 10 ppm / 15 minIDLH 100 ppm /30 minsymptoms of poisoning resemble

those of cyanide poisoningtreatment: 100 % oxygen

(amyl nitrite, sodium nitrite, 4-DMAP)

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Methaemoglobinemia –Methaemoglobinemia –inducing agentsinducing 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

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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)

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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)

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Anticholinesterase inhibitorsAnticholinesterase inhibitors

-organophosphorus pesticides and nerve agents like sarin and tabun

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Organophosphorus pesticidesOrganophosphorus 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

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Organophosphorus pesticidesOrganophosphorus 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)

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Organophosphorus pesticidesOrganophosphorus 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

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Organic solventsOrganic 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!