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# Particulate seminar

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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.

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### Particulate seminar

1. 1. Airborne ParticulateParticle Size:Statistical DescriptionInitial Physiological Deposition SiteAirborne Sampling Simulation & BiasSampling DevicesPSP and Lung Effects Michael A. Jayjock, Ph.D. CIH 1
2. 2. Particle Size Statistics 2
3. 3. Site of Deposition Depends on AerodynamicParticle 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. 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. 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. 6. 99.99 99.9 AEROSOLPercentage 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. 7. Aerosol Distribution MMAD = 10µ and GSD = 2.0 Typical for In-Plant Handling “Dusty” Plastic Powder 7
8. 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. 9. Initial Physiological Deposition Site 9
10. 10. 10
11. 11. 11
12. 12. Airborne SamplingSimulation 12
13. 13. BREATHING ZONE SAMPLINGAirborne 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 ofan imaginary line joining the ears (see diagram below). 13
14. 14. 14
15. 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. 16. INHALABLE MASSACGIH operational definition of the proportion of TOTALAirborne Aerosol Mass in the breathing zone (BZ) forany aerodynamic diameter that will be Depositedanywhere in the respiratory tree including the nose andmouth. 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. 17. ISO TR 7708 Inspirable ACGIH InhalableParticle 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. 18. THORACIC DUSTACGIH Mathematical definition of proportion ofinhalable particulate per AD size that is depositedanywhere within the lung airways and the gas-exchange region. 18
19. 19. Particle Thoracic ParticleAerodynamic 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. 20. RESPIRABLE PARTICULATE MASSACGIH operational definition for proportion ofinhalable particulate per AD size class that willbe deposited deposited in the gas-exchangeregion. 20
21. 21. Particle BMRC ACGIHAerodynamic Respirable Particle Respirable ParticleDiameter (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. 22. Sampling Devices 22
23. 23. 37mm Closed Faced Cassettes For “Total” Aerosol 23
24. 24. 37mm Cassette showing open-faced option 24
25. 25. Inlet of an open-faced filter 25
26. 26. 37 mm filter in a Cyclone 26
27. 27. 27
28. 28. Inhalable Dust Sampler 28
29. 29. 29
30. 30. 30
31. 31. British Medical Research Council (BMRC)penetration curve for respirable particlesshowing 50% cut point at 5µm. 31
32. 32. Sampling Bias 32
33. 33. 33
34. 34. 34
35. 35. PSP and Lung Effects 35
36. 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. 37. Oberdorster, G: Toxicokinetics and Effects of Fibrous and Nonfibrous Particles, Inhalation Toxicology, 14: 29-56, 2002 Pulmonary Retention Kinetics and Effects ofPoorly 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. 38. Oberdorster (op. cit.)“Morrow (1988) hypothesized – based on athorough 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 volumetricoverloading of the macrophages resultingeventually in a failure to actively moveparticles toward the mucociliary escalator.”{emphasis added} 38
39. 39. Oberdorster (op. cit.)“He [Morrow] estimated that a phagocytizedparticle volume of about 6% of the normalmacrophage volume signals the beginning ofthe impaired function, and when 60% of thenormal alveolar macrophage volume is filledwith phagocytized particles its clearancefunction will completely cease.” 39
40. 40. Oberdorster (op. cit.)“Indeed, plotting the retained particle volumein lungs of rats after long-term exposure todifferent particle types against measuredclearance rates demonstrated the correlationbetween clearance rate and retained dustvolume convincingly, as is show in Figure 3.”{emphasis added} 40
41. 41. Oberdorster (op. cit.) 41
42. 42. What Specifically Does Morrow Say About theData 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. 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. 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. 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. 46. Morrow RecommendationModify any unit density PNOC WEL relativeto the density of the material in question.For example, Portland Cement has a densityof about 3.15 g/cc. Any PNOC WEL forthese particles should be increased by thedensity of the particle; that is, the 8 hourWEL should be 3.1 times higher than the unitdensity WEL of 3.1 mg/m3. 46