Toxicology: Carbon Monoxide and Cyanide

Toxicology

• Toxicology is a branch of pharmacology
• It studies, regulates, and treats adverse effects in humans
• These effects come from chemical exposure at work or in the environment

Air Pollutants: Carbon Monoxide

• Carbon monoxide (CO) is an odorless, colorless gas
• CO has a high affinity for hemoglobin
• The threshold limit value for an 8-hour workday is 25 ppm.
• CO causes tissue hypoxia
• Initial symptoms are headache and confusion
• Symptoms then progress to decreased visual acuity, tachycardia, syncope, coma, seizures, and death
• In pregnant women, exposure to elevated CO levels during critical fetal development may cause fetal death or birth defects
• Treatment includes removing the source and administering 100% oxygen

Air Pollutants: Cyanide

• Cyanide is a toxic by-product of fire
• Source: burning synthetic rubber and wool
• Cyanide inhibits cellular respiration by binding to cytochrome C oxidase
• It results in metabolic acidosis
• Symptoms are similar to carbon monoxide poisoning
• Symptoms include headache, dyspnea, drowsiness, seizure, and coma
• Skin may appear flushed ("cherry red")
• Venules in the retina appear bright red
• Breath may have a bitter almond odor
• Treatment involves hydroxocobalamin (binds cyanide, forms cyanocobalamin for renal excretion)
• Nitrites are also used (oxidize Hb to methemoglobin, which binds cyanide, reducing toxicity)

Air Pollutants: Sulfur Dioxide

• Sulfur Dioxide is a colorless, irritating gas
• Forms from the combustion of fossil fuels
• Forms sulfurous acid on contact with moist mucous membranes
• This causes pathologic effects
• The primary sign of exposure is conjunctival and bronchial irritation
• Heavy exposure may lead to delayed pulmonary edema
• Treatment involves removal from exposure
• Also treat relief of irritation and inflammation

Air Pollutants: Nitric Oxide

• Nitric oxide is a brownish irritant formed in fires and silage on farms
• Causes deep lung irritation and pulmonary edema
• Farm workers exposed to high concentrations in enclosed silos may die rapidly of acute pulmonary edema
• There is no specific treatment
• Reduce inflammation and pulmonary edema

Air Pollutants: Ozone

• Ozone is a bluish irritant gas
• Produced in air and water purification devices and in electrical fields
• Causes irritation and dryness of mucous membranes
• Chronic exposure causes bronchitis, bronchiolitis, pulmonary fibrosis, and emphysema
• There is no specific treatment
• Reduce inflammation and pulmonary edema

Solvents: General Information

• Solvents used in industry and for cleaning contribute to hydrocarbon exposure and air pollution

Solvents: Halogenated Aliphatic Hydrocarbons

• Includes carbon tetrachloride, chloroform, and trichloroethylene
• Potent CNS depressants
• Acute effects include nausea, vertigo, locomotor disturbances, headache, and coma
• Chronic exposure leads to hepatic dysfunction and nephrotoxicity

Solvents: Aromatic Hydrocarbons

• Includes benzene, toluene, and xylene
• Acute exposure causes CNS depression with ataxia and coma
• Long-term exposure to benzene is associated with hematotoxicity and hematological malignancies such as leukemia
• Benzene is a known human carcinogen, unlike toluene or xylene
• Removal from exposure is the only way to reduce toxicity

Pesticides: Classes

• The three major classes of pesticides are:
• Chlorinated hydrocarbons (DDT and its analogs)
• Acetylcholinesterase inhibitors (carbamates, organophosphates)
• Botanical agents (nicotine, rotenone)

Pesticides: Chlorinated Hydrocarbons

• Chlorinated hydrocarbons are persistent, poorly metabolized, lipophilic chemicals
• They exhibit significant bioaccumulation
• This means increasing concentration in the environment leads to accumulation in biological tissues
• Chlorinated hydrocarbons block physiologic inactivation in sodium channels of nerve membranes
• This causes uncontrolled firing of action potentials
• Tremor is usually the first sign of acute toxicity
• It may progress to seizures
• There is no specific treatment available
• Chlorinated hydrocarbons are prohibited in North America and Europe

Pesticides: Cholinesterase Inhibitors

• Includes carbamates (aldicarb, carbaryl) and organophosphates (malathion, parathion)
• These have short environmental half-lives
• Cholinesterase inhibitors increase muscarinic and nicotinic cholinergic activity
• Signs and symptoms include pinpoint pupils, sweating, salivation, bronchoconstriction, vomiting, and diarrhea
• CNS stimulation is followed by depression, muscle fasciculations, weakness, and paralysis
• Common cause of death is respiratory failure
• Treatment includes atropine to control muscarinic effects
• Also use pralidoxime to regenerate cholinesterase

Pesticides: Botanical Insecticides

• Includes nicotine and nicotinoids
• These cause excitation followed by paralysis of ganglionic, CNS, and neuromuscular transmission
• Treatment is supportive
• Rotenone causes GI distress when ingested, and conjunctivitis and dermatitis after direct contact
• Treatment is supportive

Herbicides: Glyphosate

• Glyphosate is the principal ingredient in Roundup
• Exposure causes significant eye and skin irritation
• It can be fatal if ingested in high quantities
• Treatment is supportive

Herbicides: Paraquat

• Paraquat is non-toxic unless ingested
• Initial effect is GI irritation with hematemesis and bloody stools
• Progressive pulmonary impairment occurs
• This results in severe pulmonary fibrosis and death
• Acetylcysteine and salicylate may be beneficial

Environmental Pollutants: Polychlorinated Biphenyls (PCBs)

• PCBs were used extensively in manufacturing electrical equipment
• Until their potential for environmental damage was recognized
• They are poorly metabolized, lipophilic, and highly persistent in the environment
• They accumulate in the food chain
• Due to their estrogen-like effects, PCBs are endocrine disruptors
• Dermatotoxicity is the most common effect
• Dermatotoxicity can include acne, erythema, folliculitis, and hyperkeratosis
• Food is the major source of PCBs in humans
• Epidemiologic studies correlate PCBs with health effects

Environmental Pollutants: Dioxins

• Dioxins are unwanted byproducts of the chemical industry
• They are chemically stable and highly resistant to environmental degradation
• Exposure causes dermatitis and chloracne
• Evidence suggests carcinogenic and teratogenic effects in humans

Environmental Pollutants: Asbestos

• Asbestos is a group of naturally occurring long, flexible mineral fibers
• Commonly contains silicon
• It is poorly metabolized and lipophilic, highly persistent, and accumulates in the food chain
• Inhalation of asbestos fibers can cause asbestosis
• Asbestosis is a fibrotic lung disorder
• Asbestos is associated with several cancers
• Includes lung cancer, mesothelioma, and cancers of the GI tract