FACTORS INFLUENCING THE DOSE FOR AEROSOLS

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FACTORS INFLUENCING THE DOSE FOR AEROSOLS
Yves Alarie, Ph.D Professor Emeritus
University of Pittsburgh,USA
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A. FACTORS INFLUENCING TOTAL DOSE a) Concentration
in air, C, (mg/m3) or (mg/L) or (mM/L) or
fibers/cc or mppcf or any appropriate unit of
mass or number of particles but not
ppm. b) Particle size, which will determine the
fraction of aerosol deposited. This fraction is
called a and is given in . c) Minute
ventilation, MV, which is determined by tidal
volume (VT) and number of breaths per minute (f),
i.e., VT f. d) Duration of exposure in minutes
(t). e) Body weight (kg) or body surface area
(m2) or lung surface area (m2 70m2 in adult
humans).
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To get a ball park figure, assume 50 (0.5) for
a if particle size is not known. Thus, if a
human is exposed at a concentration of 1mg/L for
a period of 60 minutes and has a VT of 800 ml and
f of 15/minute the total dose received would be
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This value can then be divided by body weight,
etc. for a true expression of dose. As can be
seen, we now have the proper units for toxicity
instead of just having an exposure concentration
in mg/L or mg/m3 or ppm. Comparisons of total
dose received can be made between various animal
species exposed at the same concentration, on the
basis of mg/kg of body weight or mg/m2 of body
surface area or pulmonary surface area, or for
surface area of any portion of the respiratory
tract.
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• The same formula is used to calculate the
  number of fibers deposited in the respiratory
  tract.
• Thus, again assuming 0.5 for a, if a human is
  exposed at a permissible exposure level (PEL of
  OSHA) of 0.2 fibers/cc of asbestos fibers, and is
  exposed for 8 hours, assuming again a VT of 800
  ml and f of 15/min, we would have the following

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• B. FACTORS AND MECHANISMS AFFECTING TOTAL
  DEPOSITION AND REGIONAL DEPOSITION OF AEROSOLS
• The factors affecting deposition sites in the
  respiratory tract are
• Size
• Shape
• Density
• The above 3 characteristics are taken into
  account simultaneously for particles gt 0.5 µm by
  experimental determination of their aerodynamic
  mass equivalent diameter and for particles lt0.5
  µm only the size is important, as presented
  above.

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- Electrostatic attraction (depends on chemical
composition) between the particle and the surface
of the respiratory tract, may play a role but is
difficult to investigate.- Hygroscopicity
(depends on chemical composition) since a small
particle can grow upon entering the 100 RH of
the respiratory tract. Also we must take into
account the following factor Pattern of
pulmonary ventilation including nose vs. mouth
breathing, as well as volume and frequency of
each breath.
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There are 5 major physical mechanisms by which
airborne particle deposition occurs in the
respiratory tract. These are depicted in the
diagram below and explained below. For
impaction, sedimentation and diffusion,
mathematical equations have been developed a
long time ago and a look at these equations is
useful to understand each mechanism and are used
to calculate deposition in the respiratory tract.
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1. Impaction, InertiaWhen an obstacle exists in
the path of the airflow, or bifurcations or
tortuous paths occur such as in the nose or
tracheobronchial tree, small particles will
follow the air flow lines but large particles,
because of greater inertia are unable to change
direction and will impact.Note Impaction is the
most important mechanism of deposition for
particle gt 3 µm in the nasopharyngeal area and
central airways of the lung.
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2. Sedimentation, Settling All particles with
density greater than air experience a downward
force due to gravity. Thus, a particle
accelerates downward until its velocity increases
to the point where the retarding force due to its
motion through air just balances its weight. If
a particle is spheric and small enough so that
viscous forces are the primary resistive forces,
Stokes law applies to predict retarding
forces.
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3. Diffusion, Brownian Movement Motion caused
by random molecular collision, this process can
be described as follows It is
important for particles lt 0.5 µm. Important to
remember that particle diameter is the only
factor. Diffusion will be the most important
mechanism of deposition at the alveolar level.
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4. Electrostatic Attraction All aerosol particles
have a (non-metallic) or - (metallic) charge
which may affect deposition. However, little is
known about the effect of charge except for
highly charged particles which can occur in
freshly generated particles. Important for
polymeric fibers, proteins (synthetic or natural)
which can hold a high charge. 5. Interception
Of importance for fibers as the inspired air
comes in close contact with a surface. Fiber
deposition models are less well developed than
for particles.
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C. DEPOSITION CALCULATIONS AND RESULTS From the
above, calculations of deposition according to
aerodynamic particle size have been made for the
various regions of the respiratory
tract a) Nasal-Pharyngeal (N-P) b) Tracheo-Bronch
ial (T-B) c) Pulmonary (P) These are presented
below in Figures 2 and 3 and a quick summary is
presented in Table 1.
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C. MAN VS. LABORATORY ANIMAL With aerosol
exposures and laboratory animals, it is important
to recognize that although the same particle size
may be used, deposition sites and clearance rates
are likely to be different. Some general
conclusions a) The major factor controlling net
dose received seems to be minute ventilation and,
therefore, the small animals will receive a
higher total dose because of their higher minute
ventilation to body weight ratios. However,
there is variation even between animals of same
species, and deposition sites will vary from
deposition sites in humans despite similar
particle size being used.
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b) The smaller the animal, the larger the
probability of nasal retention. A 2 µm particle
has about the same probability of being retained
in the mouse nose as an 8 µm particle in man.
Important for large particles. c) The larger the
particles are above 3 µm the more chance of
difference in regional deposition with humans.
Total net dose may be the same but biological
effects may be different because the deposition
sites and clearance rates are different.(5) In
particular, clearance rates vary widely between
different species.(6) In general, clearance in
rats and mice is faster than in humans, monkeys
or guinea pigs.
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d) To have the same relation with humans between
atmospheric particulate concentration and rate of
deposition of particles in the lungs, fairly
uniform particles around 1-3 µm (MMD) seems to be
highest to use with small rodents, this would be
defined as inhalable or inspirable and would
also be classified as respirable particles for
small laboratory animals. See below for the
descriptions and definitions of these
terms. Compare the results obtained below (Figure
4) in rats and hamsters to the results obtained
in humans (Figure 3).