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Key Principles of Toxicology and Exposure

Principle 1: Using Toxic Syndrome Recognition for Rapid Diagnosis and Empiric Therapy

  • Chemical Classes
    • Toxic chemicals can often be grouped into classes, whereby all the chemicals in a given class cause similar human health effects.
    • These constellations of toxic effects or toxic syndromes comprise a set of clinical "fingerprints" for groups of toxins.
    • All of the toxins associated with a given toxic syndrome are treated similarly.
  • Emergency Treatment
    • During the early phases of a toxic chemical emergency, when the exact chemical is often unknown, identification of the toxic syndromes that are present can be a useful decision-making tool.
    • Toxic syndromes are easily identified with only a few observations, such as:
      • Vital signs
      • Mental status
      • Pupil size
      • Mucous membrane irritation
      • Lung exam for wheezes or rales
      • Skin for burns, moisture, and color
    • The identification of the constellation of signs and symptoms is all that is needed to diagnose and treat a life-threatening condition (e.g., respiratory arrest).
    • Once the life-threatening crisis has been averted and time passes, more specific information from the history or diagnostic test results will guide additional therapeutic decisions and patient disposition.

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Principle 2: Route of Exposure is a Determinant of Toxicity

  • A chemical's physical state and the route of exposure influence toxicity.
  • The chemical's state often determines the route of exposure.
  • For many chemicals, the toxic effects occur at the site of absorption.
    • Inhalation exposure- Gases, vapors, airborne powders, and aerosolized liquids are inhalation risks.
      • Irritant gases attack the water in the respiratory mucosa and eye, causing burning pain, irritation, and copious secretions at the site of contact.
      • Inhalation exposure also allows some rapid entry into the systemic circulation, causing toxic effects distant from the entry route.
      • Hydrogen cyanide is a gas that rapidly enters the circulation through the lung and causes loss of consciousness, seizures, cardiac dysrhythmias, hypotension, and possible death in a matter of minutes after the exposure.
    • Dermal exposure - Chemicals in contact with the skin can cause local effect but may also enter the systemic circulation and cause effects at distant sites from the entry route.
      • Organophosphate insecticides are fat-soluble chemicals that rapidly penetrate the skin and enter the blood stream to circulate to distant sites.
      • Skin exposure can delay onset of systemic effects as compared with the rapid entry through the lung.

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Principle 3: The Dose Makes the Poison

  • Dose - response
    • Evaluating clinical effects based on the amount of exposure is a basic toxicology principle called dose-response.
    • The dose is the total amount of chemical absorbed during an exposure.
    • Dose depends on the concentration of the chemical and duration (contact time) of the exposure. Chemicals cause predictable toxic effects based on the dose.
      • Ethanol is a good example. Incremental increases in blood ethanol levels result in predictable increases in alteration of consciousness (signs of inebriation), poor coordination, and eventually coma/respiratory depression, and finally death.
  • Exposure
    • Duration of exposure is one important factor affecting the dose
    • High concentrations over a long duration are more likely to produce adverse health effects than the same or lower concentration over a shorter exposure period.
      • Example 1, Dermal exposure - an acid placed on the skin will cause more tissue destruction the longer it stays in contact with the tissues. If the acid is immediately washed off the skin, injury is limited.
      • Example 2, Inhalation exposure - The longer a victim is allowed to breathe toxic chemicals, the greater the dose of exposure.
  • Application of dose-response principles
    • Applying the above dose-response principles can guide patient assessment to toxic chemical exposures.
    • Patients who have higher concentrations and longer durations of exposure result in greater doses to the victim and will more likely have harmful effects.
    • Those receiving larger doses need more urgent attention and possibly life-saving interventions than those receiving smaller doses (especially if asymptomatic).

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References

Content adapted from:

Kirk MA, Deaton ML. Bringing order out of chaos: effective strategies for medical response to mass chemical exposure. Emerg Med Clin North Am. 2007 May;25(2):527-48. [PubMed Citation]

Additional References:
  1. Madsen J. Chemical terrorism: Rapid recognition and initial medical management. UpToDate®. Last update was September 13, 2017. Literature review current through September 2017. Access unavailable without a personal or institutional account at: UpToDate
  2. Chemical warfare agents: an overview (NIH VideoCasting and Podcasting, 1 hour 11 minutes) (James M. Madsen, MD, MPH, FCAP, FACOEM COL, MC-FS, US Army)
  3. Workplace Safety & Health Topics - Skin Exposure & Effects (HHS/CDC/NIOSH)
  4. ToxTutor (HHS/NIH/National Library of Medicine)