Childhood Asthma/Tobacco Smoke

Introduction

Characteristics

Fate and Transport

Exposure Pathway

Methods for Monitoring in the Environment

Methods for Measuring Human Exposure

Strategies for Preventing or Controlling Exposure


Respiratory Harmful Effects

Deposition, Absorption, and Metabolism

Dose-Response Relationship

Organ Sites of Toxicity

Biomarkers

Risk Assessment/Risk Management Considerations

References

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Deposition, Absorption, and Metabolism of Environmental Tobacco Smoke (ETS)

Deposition of ETS particulates in respiratory system

  • Depends on several factors: particle size, influence on impaction, sedimentation and diffusion
    • Larger particles impact at bend in airways or lungs
    • Particles between .02 um and .05um impact less
    • Sidestream smoke (SS) particles may grow in size from moisture in respiratory tract
    • Figure below shows that higher deposition occurs at very small <.01 um and large >1.0 particle size)
      NOTE: Mean diameter of ETS is between 0.1 to 0.14 um
  • Also depends on respiratory pattern
    • Children more breaths per/minute than adults and take in more oxygen than adults therefore at risk for increase deposition
  • Presence of electrical charge may increase deposition, but not enough information describing the effect of charge on deposition of sidestream smoke
  • Sidestream smoke deposition study (Surgeon General’s Report, 1986)
    • Eleven human volunteers breathing in ETS through the mouth, taking 12 breaths/min, had 11%deposition
  • Region of Deposition
    • Upper Respiratory Tract (larynx and above)
    • Tracheobronchial (trachea to and including terminal bronchioles)
    • Pulmonary Region (respiratory bronchioles and beyond)
    • Note: Particle size is major determinant of both regional and total deposition
  • Deposition of particles are not uniform within each region

Deposition of ETS particulates in children’s growing respiratory system

  • Through a mathematical growth model it is estimated that tracheobronchial depositions per kilogram of body weight for 5um particles is 6 times higher in a resting newborn than in a resting adult
  • Particles the size of SS deposit 2-fold or 3-fold higher in infant tracheobronchial region than in adults

Dose of ETS through deposition of particulates

  • Dose of ETS to the respiratory tract is product of mass in inhaled air and deposition fraction
  • To estimate dose, the content of smoke in inhaled air and the volume of air expired
  • Mass deposition in respiratory tract can be estimated if atmospheric burden of cigarette particulates, minute volume and deposition fraction
    • For example Smoke Concentration = 500ug/m^3, Minute volume of 12 liters per minute and deposition fraction of 11%

Markers of Absorption

  • Measurement of nicotine in the blood or urine indicates exposure to gas phase of nicotine
    • Nicotine absorbed through the mucous membranes of the mouth, bronchial tree and alveolar capillary membrane
    • ETS not as acidic as mainstream smoke (MS) thereby allowing absorption into the mouth and nose
      ** NOTE: Approximately twice as much nicotine is emitted in sidestream than mainstream smoke.
  • Cotinine (metabolite of nicotine) better measurement of absorption of ETS nicotine because
    • Longer half-life than nicotine and cotinine has a longer half-life than nicotine and high specificity
    • Levels can be used to produce quantitative estimates of nicotine absorption
  • Other markers include carbon monoxide and thiocyanate
    • Carbon monoxide binds to hemoglobin and hydrogen cyanide metabolized by the liver to become thiocyanate
    • However, carbon monoxide and cyanide found in nature therefore maybe difficult to determine if exposure from ETS or from environment

Absorption of Nicotine (Mainstream smoke)

  • Absorption depends on pH
  • Nicotine is weak base with pKa= 8.0, which means 50% will be ionized at pH = 8.0
  • Typical cigarette smoke acidic pH = 6.0 to 5.5 therefore most nicotine ionized
  • Absorption occurs in spleen, liver, lung and brain; they have high affinity for nicotine
  • Renal excretion also depends on urinary pH and urinary flow; on average about 5-10% is excreted

Metabolism of Constituents of ETS-- Nicotine

  • Nicotine carried on droplet of tar and in vapor phase
  • Absorped through alveoli in lungs and then into blood
  • In blood about 60% ionized because blood pH 7.4
  • Distributed extensively to body tissues (about 2.6 times amount predicted by the product of nicotine concentration in blood times body weight)
  • Metabolized mostly by liver and a little by the lungs
  • Nicotine metabolized into major metabolites cotinine and nicotine-n`-oxide (shown below)
  • Major metabolites are shown below