Michael Jayjock's lecture. Refers to: Morrow, P.E. et al: Chronic Inhalation Study Findings as the basis for Proposing a New Occupational Dust Exposure Limit, International Journal of Toxicology March/April 1991 10: 279-290.

1. Airborne Particulate
Particle Size:
Statistical Description
Initial Physiological Deposition Site
Airborne Sampling Simulation & Bias
Sampling Devices
PSP and Lung Effects
Michael A. Jayjock, Ph.D. CIH
1

2. Particle Size Statistics
2

3. Site of Deposition Depends on Aerodynamic
Particle Size or Aerodynamic Diameter (AD)
• AD is determined by the settling
velocity of the particle in normal air.
• Any Particle with aerodynamic
diameter of X falls at the same speed
as a UNIT DENSITY SPHERE
with X diameter.
3

4. Definitions
• Mass Median Aerodynamic Diameter
(MMAD) – The AD where 50% of the
aerosol is of larger AD and 50% smaller.
The AD at the 50th percentile.
• Geometric Standard Deviation (GSD): A
measure of the width (or dispersion) of the
distribution. AD at the 84th percentile
divided by the AD at the 50th percentile
4

5. Example: Typical In-plant aerosol
from a “dusty” Plastic Powder
• MMAD = 10 microns
• GSD = 2
• 50th percentile AD = 10 microns
• 84th percentile AD = 20 microns
• 16th percentile AD = 5 microns
Compare to 50% “cut point for respirable
particulate of 4 or 5 microns – only about
10% of the airborne K120n is respirable
5

6. 99.99
99.9
AEROSOL
Percentage of Mass in Particles
99
MMAD = 10, GSD = 2.0
Less than Stated Size
90
70
50
30
10 MMAD = 10
1
0.1
0.01
1 10 100
Aerodynamic Diameter (microns)
6

7. Aerosol Distribution MMAD = 10µ and GSD = 2.0
Typical for In-Plant Handling
“Dusty” Plastic Powder
7

8. Definitions/Classifications
• PNOC – airborne particulate not otherwise
classified
• PSP – poorly soluble airborne particulate
• Lung Overload – dose rate of particulate that
exceeds the normal rate of clearance leading to an
even lower rate (or cessation) of clearance and
secondary toxicity as a result.
• Particulate with Inherent Toxicity – particulate
that when in contact with pulmonary tissue can
injure that tissue irrespective of overload.
8

9. Initial Physiological
Deposition Site
9

10. 10

11. 11

12. Airborne
Sampling
Simulation
12

13. BREATHING ZONE SAMPLING
Airborne Mass is measured in the breathing zone of the worker,
which is an imaginary hemisphere of approximately 30 cm,
extending in front of their face and measured from the midpoint of
an imaginary line joining the ears (see diagram below).
13

14. 14

15. THREE MEASUREMENT/SIMULATION CLASSES
OF AIRBORNE PARTICULATE
DOSE/EXPOSURE
• INHALABLE: any particle that
penetrates/deposits past the nose and mouth.
• THORACIC: particles that penetrate/deposit
anywhere within the lung airways and the gas-
exchange region
• RESPIRABLE: particles that penetrate/deposit
exclusively into the gas-exchange region or
pulmonary region of the deep lung.
15

16. INHALABLE MASS
ACGIH operational definition of the proportion of TOTAL
Airborne Aerosol Mass in the breathing zone (BZ) for
any aerodynamic diameter that will be Deposited
anywhere in the respiratory tree including the nose and
mouth.
SI(d) = 50% x (1 + e-0.06d )
for 0 < d ≤ 100µm
where SI(d) = collection efficiency for
particles with aerodynamic diameter
d in µm.
16

17. ISO TR 7708 Inspirable ACGIH Inhalable
Particle Aerodynamic
Mass Fraction Particle Mass (IPM)
Diameter (µm)
(%) (%)
0 100 100
1 - 97
2 - 94
5 - 87
10 73 77
20 - 65
30 52 58
40 - 54.5
50 - 52.5
60 34 -
100 20 50
185 0 Not defined
17

18. THORACIC DUST
ACGIH Mathematical definition of proportion of
inhalable particulate per AD size that is deposited
anywhere within the lung airways and the gas-
exchange region.
18

19. Particle Thoracic Particle
Aerodynamic Mass (TPM) (%)
Diameter (µm)
0 100
2 94
4 89
6 80.5
8 67
10 50
12 35
14 23
16 15
18 9.5
20 6
25 2
19

20. RESPIRABLE PARTICULATE MASS
ACGIH operational definition for proportion of
inhalable particulate per AD size class that will
be deposited deposited in the gas-exchange
region.
20

21. Particle BMRC ACGIH
Aerodynamic Respirable Particle Respirable Particle
Diameter (µm) Mass (RPM) (%) Mass (RPM) (%)
0 100 100
1 98 97
2 92 91
3 82 74
4 68 50
5 50 30
6 28 17
7 0 9
8 - 5
10 - 1
21

22. Sampling Devices
22

23. 37mm Closed Faced Cassettes
For “Total” Aerosol
23

24. 37mm Cassette showing open-faced option
24

25. Inlet of an open-faced filter
25

26. 37 mm filter in a Cyclone
26

27. 27

28. Inhalable Dust Sampler
28

29. 29

30. 30

31. British Medical Research Council (BMRC)
penetration curve for respirable particles
showing 50% cut point at 5µm.
31

32. Sampling Bias
32

33. 33

34. 34

35. PSP and Lung Effects
35

36. PSP RESPIRABLE
vs.
Non-Respirable Aerosol Particulate
• NON-RESPIRABLE: Insoluble Airborne Particulate
that is deposited in Upper Respiratory Track (ciliated
region and above) will go to GI track and be excreted
quickly.
• RESPIRABLE: Insoluble Airborne particulate that
penetrates to the deep lungs (pulmonary region) has a
much longer residence time in the lung; thus, chronic
exposure is more subject to lung “over-load” effect.
36

37. Oberdorster, G: Toxicokinetics and Effects of Fibrous and
Nonfibrous Particles, Inhalation Toxicology, 14: 29-56, 2002
Pulmonary Retention Kinetics and Effects of
Poorly Soluble Particulate of Low Toxicity (PSP)
“…if the deposition rate of the inhaled
particles exceeds their mechanical clearance
rate…, the retention half-time is significantly
increased, reflecting an impaired or
prolonged alveolar macrophage-mediated
clearance function with accumulation of lung
burden.”
37

38. Oberdorster (op. cit.)
“Morrow (1988) hypothesized – based on a
thorough evaluation of a number of long-
term inhalation studies with particles in rats –
that the impairment of alveolar macrophage-
mediated clearance is due to a volumetric
overloading of the macrophages resulting
eventually in a failure to actively move
particles toward the mucociliary escalator.”
{emphasis added}
38

39. Oberdorster (op. cit.)
“He [Morrow] estimated that a phagocytized
particle volume of about 6% of the normal
macrophage volume signals the beginning of
the impaired function, and when 60% of the
normal alveolar macrophage volume is filled
with phagocytized particles its clearance
function will completely cease.”
39

40. Oberdorster (op. cit.)
“Indeed, plotting the retained particle volume
in lungs of rats after long-term exposure to
different particle types against measured
clearance rates demonstrated the correlation
between clearance rate and retained dust
volume convincingly, as is show in Figure 3.”
{emphasis added}
40

41. Oberdorster (op. cit.)
41

42. What Specifically Does Morrow Say About the
Data and its Implications for PNOC – WELs ?
• “The results illustrate a progressive decrease in
alveolar clearance rates once an excessive
pulmonary burden is attained.”
• “In this context, loss of mobility represents a
failure of particulate clearance to proceed,
leading to increased intersitialization of particles
and to the induction of a host of dysfunctional and
pathologic conditions of a seemingly generic
nature.” [emphasis added]
Morrow, P.E. et al: Chronic Inhalation Study Findings as the basis for
Proposing a New Occupational Dust Exposure Limit, J of Am. Coll. Tox,
10, 2, 1991 42

43. Morrow (op. cit.)
• “…dust overloading represents a serious,
confounding complication to the toxicological
assessment, one in which the intrinsic toxicity of
the test material is either masked or modified by
the nonspecific effects of dusts on macrophage
transport.”
• “The foregoing resume of studies indicates that
overloading effects on dust clearance can be
expected to occur with any persistently retained
dust…”
43

44. Morrow’s Arguments for a PNOC Respirable Mass
WEL of less than 1 mg/m3 (Morrow op. cit.)
• For UNIT DENSITY Particles
(1 mg/m3)(7.2m3/day)(240days/365days) =
4.7 mg/day
• Assuming a clearance half life of 200 days (k =
0.0035/day) THEN (0.0035/day)
(Burden) = 4.7 mg/day
• Lung Burden = 1340 mg/1000g Lung
• Values > 1mg/g lung are associated with overload
in the Rat.
44

45. Continuation of Morrow’s Arguments for a PNOC
Respirable Mass WEL of less than 1 mg/m3
(Morrow op. cit.)
• Breathing rate of 7.2 m3/day is NOT
conservative.
• Clearance rate assumed for humans is
typical but it is NOT conservative.
• Xerox Corporation’s HHRC recommended
and Xerox Corporation implemented an
internal respirable PNOC limit of 0.4
mg/m3 in 1990.
45

46. Morrow Recommendation
Modify any unit density PNOC WEL relative
to the density of the material in question.
For example, Portland Cement has a density
of about 3.15 g/cc. Any PNOC WEL for
these particles should be increased by the
density of the particle; that is, the 8 hour
WEL should be 3.1 times higher than the unit
density WEL of 3.1 mg/m3.
46