Occupational and Specific Environmental Toxins
Halogenated hydrocarbons
Halogenated hydrocarbons are usually volatile, and exposure can be through ingestion or inhalation. They are lipid soluble and can pass through the blood-brain barrier. Most will depress the central nervous system (CNS) when acute exposures are high.
- Carbon tetrachloride: Individuals can be exposed to carbon tetrachloride through consumption of contaminated drinking water. Although transient, low-level inhalation of carbon tetrachloride can produce irritation of the eyes and respiratory system. Higher levels, whether inhaled or ingested, can produce nausea, vomiting, stupor, convulsions, coma, and death from CNS depression . Carbon tetrachloride undergoes a cytochrome P450mediated metabolic activation to produce free radicals that are oxidize essential cellular components. A nonlethal acute exposure can occur within a period of several hours to several days and produce liver and kidney damage.
- Chloroform: The adverse effects associated with chloroform exposure are similar to those with carbon tetrachloride. Exposures can occur through ingestion or inhalation, and high enough levels will result in nausea, vomiting, dizziness, headaches, and stupor. Chloroform can also sensitize the heart to catecholamine-induced arrhythmias. Chloroform is hepatotoxic and nephrotoxic as a result of its metabolic activation.
Aromatic hydrocarbons
As with the halogenated hydrocarbons, aromatic hydrocarbons tend to be volatile, and exposure can occur through inhalation and ingestion. Large acute exposures can cause CNS depression, and lead to cardiac arrhythmias through sensitization of heart cells to catecholamines. However, other aspects of their toxicological profile can differ significantly from that of the halogenated hydrocarbons.
- Benzene: Approximately half of the national exposure to benzene occurs through tobacco smoke. Chronic benzene exposure in humans produces hematopoietic toxicities, of which the most serious are agranulocytosis and leukemia, particularly acute myelogenous leukemia. Nonoccupational exposures to benzene can occur as a result of combustion of fossil fuels, including automobile gasoline, and by consumption of contaminated water.
- Toluene: Automobile emissions are the principal source of exposure in ambient air, whereas indoors exposure occurs from the use of household products containing toluene-like degreasers, certain paints and primers, and furniture polish. Acute and chronic exposure to toluene can produce CNS depression, with symptoms including drowsiness, ataxia, tremors, impaired speech, hearing, and vision. Chronic exposure may also produce some damage to the liver and kidneys. Deaths have occurred at high levels of exposure.
Alcohols
- Methanol (wood alcohol) and ethylene glycol: These primary alcohols are themselves relatively nontoxic and cause mainly CNS sedation. However, methanol and ethylene glycol are oxidized to toxic products formic acid in the case of methanol, and glycolic, glyoxylic, and oxalic acids in the case of ethylene glycol. Fomepizole inhibits this oxidative pathway, preventing the formation of toxic metabolites, and allows the parent alcohols to be excreted by the kidney. Coma, seizures, hyperpnea, and hypotension all suggest that a substantial portion of the parent alcohols has been metabolized to toxic acids.
- Isopropanol: This secondary alcohol is metabolized to acetone via alcohol dehydrogenase. Acetone cannot be further oxidized to a carboxylic acids and, therefore, shows only limited acidemia and toxicity.
Pesticides
Pesticides are a large class of chemicals designed to kill organisms that society considers to be unhealthy, a nuisance, or destructive. Although their use is often controversial, they have had a significant impact on public health through the reduction of insect-borne diseases, such as yellow fever and malaria, and they have increased crop yields in agriculture. A large variety of different pesticides are currently used throughout the world. Some of the more commonly used compounds are considered here.
- Organophosphosphate and carbamate insecticides: These agents constitute two major classes of insecticides used in the United States and throughout the world. They exert their mammalian toxicity through inhibition of acetylcholinesterase, with subsequent accumulation of excess acetylcholine.
- Pyrethroids: The pyrethroids exert their mammalian and insect toxicity by extending the open time of sodium channels throughout the central and peripheral nervous systems. Symptoms of toxicity include loss of coordination, tremors, convulsions, and burning and itching sensations. Pyrethroids can also act as dermal and respiratory allergens, and exposure can lead to contact dermatitis or asthma-like symptoms. Death, when it occurs in humans, is usually due to respiratory failure. Fortunately, the pyrethroids are much more toxic to insects due to their limited ability to eliminate these compounds.
- Rotenone: Rotenone is used primarily as an insecticide and is applied to a wide variety of crops. It acts by inhibiting the oxidation of the reduced form of nicotinamide-adenine dinucleotide. Symptoms of poisoning include nausea and vomiting, with convulsions and death at very high exposures.
Rodenticides
In contrast to insecticides, which are often applied by spraying, the rodenticides are usually used in the form of solid baits ingested by rodents. Consequently, the public health threat posed is usually through the accidental or suicidal ingestion. The most commonly used rodenticides are the anticoagulants, such as warfarin.