Toxicology

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Toxicology is the branch of science that deals with poisons, defined as any substance that causes a harmful effect when administered, either by accident or design, to a living organism. [1] Toxicology includes not just chemicals, drugs, and biological substances, like venoms, that can cause harm when introduced into the body of a human, animal, or plant, but also certain physical phenomenon - like radiation.

Almost any chemical can be toxic; it is the dose that determines the toxic effect. As Paracelsus, the father of modern toxicology said, “Sola dosis facit venenum” (only dose makes the poison). Paracelsus, who lived in the 16th century, was the first person to explain the dose-response relationship of toxic substances. The absolute amount of a substance taken is not the only factor in determining toxicity. Drugs and chemicals can interact in the system of an organism so that the toxicity of each is increased. An example of such a combination is acetaminophen and ethanol: when combined at their respective non-toxic doses, they can produce a toxic effect [2].

Some chemicals are toxic to certain organs, others produce widespread toxicity. Cyanide is a metabolic toxin that affects the mitochondria in every cell in the body. Excessive doses of the aminoglycoside antibiotic gentamicin, are nephrotoxic and ototoxic: they accumulate in the tissue of the kidney, and poison its fundamental unit, the nephron,and also destroy hair cells of the inner ear. Substances that are not obvious poisons can also be toxic- for example wood dust, dispersed in the air of a workshop or factory, can cause damage to the lungs and sinuses of an exposed person over time.

Epidemiology

Poisoning ranks as the second leading cause of accidental injury deaths in the United States, behind motor vehicle accidents. In the United States in 2003, 28,700 people died of poisoning, with 68% of those deaths unintentional. Poison control centers listed over 2 million poison exposure cases in 2004, and emergency departments reported 577.866 visits from accidental poisoning victims. [3]

Most unintentional poisonings were caused by legal and illegal drugs, such as opioids, cocaine, NSAIDS, benzodiazepenes, along with cosmetics, cleaning substances, foreign bodies, OTC drugs, and pesticides. [4]

Quantification

The classical toxicology test has been the LD50 (lethal dose 50), which refers to the concentration of drug required to kill 50% of the test subjects (usually mice or rabbits) in a certain amount of time. The lower the LD50, the more toxic the substance is. This test can also be applied to achieve other percentages, for example the LD10 (dose to kill 10% of the subjects), or the LD100 (the minimum dose to kill all of the subjects)

General Treatment

Treatment of toxicity depends mostly on the specific toxin. However, there are general treatments that are applicable to almost every toxin. For all poisonings, the victim should be monitored for symptoms, have their vitals checked, and given supportive care such as feeding tubes, ventilation support etc.

Other treatment involves removing or neutralizing the toxin. Victims are often treated by minimizing absorption, by emptying the bowels (ipecac syrup, gastric lavage, whole bowel irrigation), diluting the toxin with water, administering activated charcoal, or topical decontamination. Another treatment option is to enhance elimination of the toxin, through multiple dose activated charcoal, surgical removal, or changing the pH of the urine. If an antidote to the toxin is available, it can be given to neutralize the toxin

Toxins

Drugs

Drugs are the main cause of toxicity in modern times. Modern drugs are specific isolated and concentrated compounds used to produce a desirable effect in the body. This leads to the ability of drugs to produce a high concentration of drug with a reasonably low amount of exposure. They often are brightly colored, and many have an attractive taste to encourage routine use of the drug. These factors lead to a high amount of overdose and therefore poisoning with drugs.

Some drugs produce side effects: toxic effects that occur at routine and therapeutic levels. This risk must be carefully weighed when choosing a drug regimen.

Acetaminophen

Acetaminophen (Tylenol®, or paracetamol), is a common OTC analgesic and antipyretic, and is the most common medication overdose. The maximum dose of acetaminophen is 4 grams per day for an adult, or 8 Extra-Strength Tylenol® tablets.

A small percentage (5%) of the active compound is metabolized in the liver by the CYP2E1 enzyme to NAPQI, a toxic metabolite that normally binds to a sulfhydryl-containing compound called glutathione. However, in large does, glutathione stores are depleted, allowing NAPQI to bind to other sulfhydryl-containing compounds in the liver, eventually leading to hepatic necrosis. In cases of massive hepatic failure, renal injury can also occur, which can lead to acute kidney failure. [5]

Long term ethanol use induces the CYP2E1 enzyme, which produces larger amounts of NAPQI from dose of acetaminophen. This combination can cause liver failure with normal doses of acetaminophen. [6]

Symptoms of acetaminophen overdose include GI disturbances, such as nausea and vomiting, abdominal pain, lack of hunger, pallor and sweating. N-acetylcysteine (NAC) can be given as treatment, as it helps to replenish the depleted glutathione stores.

Salicylates

Salicylate toxicity contains poisoning from aspirin (acetylsalicylic acid), salsalate (salicylsalicylic acid), oil of wintergreen, and other salicylates. Acute toxicity manifests itself as irritation of the GI tract, increased respiration rate, increased metabolic rate leading to fever, ringing in the ears, metabolic acidosis, urine ketone bodies, decreased blood coagulation, and low glucose concentration in the brain. Chronic toxicity often includes the above signs, along with dehydration and lethargy. A large dose can lead to coma and death.

Treatment is given by activated carbon and/or whole bowel irrigation to decrease the absorption from the GI tract, administer sodium bicarbonate to increase the pH in the urine to help enhance renal elimination, supportive care with IV fluids to correct electrolyte imbalances, and a ventilator to control breathing. In severe cases, dialysis may be used.

References

  1. Ernest Hodgson. Introduction. A Textbook of Modern Toxicology (Third Edition) page 1 Online ISBN: 9780471646778 Print ISBN: 9780471265085 Copyright © 2004 John Wiley & Sons, Inc.
  2. Draganov P. et al. Alcohol-acetaminophen syndrome. POSTGRADUATE MEDICINE. Vol 107, Num 1, 200.
  3. Poisoning in the United States: Fact Sheet. CDC. http://www.cdc.gov/ncipc/factsheets/poisoning.htm
  4. Clinical Toxicology, 2006:44:803.
  5. Chyka, P. Clinical Toxicology. Pharmacotherapy: A Pathophysioligic Approach 6th. ed. DiPiro et al. 2005.
  6. Draganov P. et al. Alcohol-acetaminophen syndrome. POSTGRADUATE MEDICINE. Vol 107, Num 1, 200.