Toxicology: Air Pollutants

Toxicology

• Toxicology is the branch of pharmacology dealing with the study, regulation, and treatment of adverse effects in humans from chemical exposure at work or in the general environment.

Air Pollutants

Carbon Monoxide

• Carbon monoxide is an odorless, colorless gas with a high affinity for hemoglobin.
• The threshold limit value for carbon monoxide is 25 ppm for an 8-hour workday.
• Carbon monoxide causes tissue hypoxia.
• Initial symptoms of carbon monoxide exposure include headache, followed by confusion, decreased visual acuity, tachycardia, syncope, coma, seizures, and death.
• In pregnant women, elevated CO levels during critical fetal developmental periods can cause fetal death or birth defects.
• Removal from the source of CO and 100% oxygen administration are treatments for carbon monoxide exposure.

Cyanide

• Cyanide is a toxic by-product of fire related to burning synthetic rubber and wool.
• Cyanide inhibits cellular respiration by binding to cytochrome C oxidase.
• Metabolic acidosis and symptoms similar to carbon monoxide poisoning result from cyanide exposure.
• Symptoms include headache, dyspnea, drowsiness, seizure, and coma.
• Skin appears flushed (“cherry red"), venules in the retina appear bright red, and breath may have a bitter almond odor.
• Hydroxocobalamin (binds cyanide to form cyanocobalamin for renal excretion) and nitrites (oxidize hemoglobin to methemoglobin, which binds cyanide) are treatments for cyanide poisoning.

Sulfur Dioxide

• Sulfur dioxide is a colorless, irritating gas formed from the combustion of fossil fuels.
• Sulfurous acid forms upon contact with moist mucous membranes, causing pathologic effects.
• The primary exposure sign is conjunctival and bronchial irritation.
• Heavy exposure can ultimately lead to delayed pulmonary edema.
• Treatment includes removal from exposure and relief of irritation and inflammation.

Nitric Oxide

• Nitric oxide is a brownish irritant formed in fires and in silage on farms.
• It causes deep lung irritation and pulmonary edema.
• Farmers exposed to high concentrations of the gas within enclosed silos may die rapidly of acute pulmonary edema.
• No specific treatment exists, but reducing inflammation and pulmonary edema is recommended.

Ozone

• Ozone is a bluish irritant gas produced in air and water purification devices and in electrical fields.
• Ozone exposure causes irritation and dryness of mucous membranes.
• Chronic exposure can cause bronchitis, bronchiolitis, pulmonary fibrosis, and emphysema.
• No specific treatment exists, but reducing inflammation and pulmonary edema is recommended.

Solvents

Halogenated Aliphatic Hydrocarbons

• Halogenated Aliphatic Hydrocarbons (carbon tetrachloride, chloroform, trichloroethylene) are potent CNS depressants.
• Acute effects include nausea, vertigo, locomotor disturbances, headache, and coma.
• Chronic exposure leads to hepatic dysfunction and nephrotoxicity.

Aromatic Hydrocarbons

• Acute exposure to Aromatic Hydrocarbons (benzene, toluene, xylene) causes CNS depression with ataxia and coma.
• Long-term exposure to benzene is associated with hematotoxicity (thrombocytopenia, aplastic anemia, pancytopenia) and hematological malignancies such as leukemia.
• Benzene is a known human carcinogen, unlike toluene or xylene.
• Removal from exposure is the only specific way to reduce toxicity.

Pesticides

• The three major classes of pesticides include chlorinated hydrocarbons (DDT and its analogs), acetylcholinesterase inhibitors (carbamates, organophosphates), and botanical agents (nicotine, rotenone).

Chlorinated Hydrocarbons

• Chlorinated hydrocarbons are persistent, poorly metabolized & lipophilic chemicals, exhibiting significant bioaccumulation.
• There is an increasing concentration of a substance in the environment due to environmental persistence and physical properties, leading to its accumulation in biological tissues.
• They block physiologic inactivation in the sodium channels of nerve membranes, causing uncontrolled firing of action potentials.
• Tremor is usually the first sign of acute toxicity and may progress to seizures.
• No specific treatment is available.
• Chlorinated hydrocarbons are prohibited in North America and Europe.

Cholinesterase Inhibitors

• Carbamates (aldicarb, carbaryl) and organophosphates (malathion, parathion) have short environmental half-lives.
• Cholinesterase inhibitors increase muscarinic and nicotinic cholinergic activity.
• Symptoms include pinpoint pupils, sweating, bronchoconstriction, vomiting and diarrhea, CNS stimulation followed by depression, and muscle fasciculations, weakness, and paralysis.
• The common cause of death is respiratory failure.
• Treatment includes Atropine to control muscarinic effects and pralidoxime to regenerate cholinesterase.

Botanical Insecticides

• Nicotine and nicotinoids 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 brand weed killer.
• Exposure to Glyphosate causes significant eye and skin irritation and can be fatal if ingested in high quantities; treatment is supportive.

Paraquat

• Paraquat is non-toxic unless ingested.
• The initial effect is GI irritation with hematemesis and bloody stools.
• Progressive pulmonary impairment occurs, resulting in severe pulmonary fibrosis and death.
• N-acetylcysteine and salicylate might be beneficial.

Environmental Pollutants

Polychlorinated Biphenyls (PCBs)

• PCBs were extensively used in manufacturing electrical equipment until their potential for environmental damage was recognized.
• They are poorly metabolized, lipophilic, and highly persistent in the environment, accumulating in the food chain.
• PCBs are endocrine disruptors due to their estrogen-like effects.
• Dermatotoxicity (acne, erythema, folliculitis, hyperkeratosis) is the most common effect.
• Food is the major source of PCBs in humans.
• Epidemiologic studies have established a correlation with PCBs.

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.

Asbestos

• Asbestos is a group of naturally occurring long, flexible mineral fibers, most commonly containing silicon.
• They are poorly metabolized, lipophilic, highly persistent in the environment, and accumulate in the food chain.
• Inhalation of asbestos fibers can cause a fibrotic lung disorder called asbestosis.
• Asbestos exposure is associated with lung cancer, mesothelioma, and cancers of the GI tract.