National Asbestos Meeting June 23-24, 2011 Asbestos Exposure and Disease

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1 National Asbestos Meeting June 23-24, 2011 Asbestos Exposure and Disease Christopher P. Weis, Ph.D., DABT. Senior Toxicologist Office of the Director National Institute of Environmental Health Science

2 Objectives Provide an overview of the characteristics of asbestos that make it poisonous. Explain what s unique about measuring exposure to asbestos. Demonstrate some of the difficulties and pitfalls of asbestos exposure measurement.

3 Ref: Seattle Post Intelligencer

4 Ref: CP Weis

5 Fiber shape and surface area are important.

6 Objectives Provide an overview of the characteristics of asbestos that make it poisonous. Explain what s unique about measuring exposure to asbestos. Demonstrate some of the difficulties and pitfalls of asbestos exposure measurement.

7 Basic Respiratory Anatomy

8 Fiber Deposition in the Lung Tremolite

9 Mechansisms of Particle Deposition in the Lung

10 Fiber Deposition in the Lung

11 Anatomy of the bronchiolar alveolus clusters

12 Gas exchange in the lung The alveolarcapillary membrane is just 0.2 microns thick! Blood volume in capillary space Is about 70 ml. Blood flow through the lung is about 5L/min.

13 Phagocytosis of asbestos fibers pulmonary alveolar macrophage cell attempting to engulf and ingest several long crocidolite asbestos fibers incomplete ingestion of asbestos fibers can lead to extensive selective release of proteolytic enzymes and ROS from the frustrated PAMs

14 Microscopic and Macroscopic Lung Abnormalities Caused by fibers Radiograph of Pleural plaques asbestos bodies ferruginous bodies Anatomy of Pleural plaques

15 High Resolution Computed Tomography (HRCT) HRCT scan of a 45 Y.O. female with secondary (take home) exposure to Taconite dust in the Upper Peninsula of Michigan. Harbut et al. (2009) Int J Occup Environ Health 15(3):

16 Objectives Provide an overview of the characteristics of asbestos that make it poisonous. Explain what s unique about measuring exposure to asbestos. Demonstrate some of the difficulties and pitfalls of asbestos exposure measurement.

17 Asbestos causes disease in the Lungs so.. Measures to estimate asbestos exposure should be focused upon relevant pathways of exposure; Exposure measures are most relevant if they estimate asbestos in the breathing zone; Activities near sources of friable asbestos cause it to stir into the nearby air. Personal Exposure Environment.

18 Site Concept Model

19

20

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22 El Dorado Activity-Based Exposures - Counting PCME Amphiboles Activity Garden - School Ratio: Personal Exposure to Reference Average Personal Exposure (f/cc) Ambient Reference Concentration (f/cc) Biking Trail Jogging Trail Baseball - Park Soccer - Park Baseball Observer Tot Lot - Park PCME: Length (> 5 um), Width (>0.25 um), Aspect Ratio (Length:Width Ratio > 3:1)

23 Objectives Provide an overview of the characteristics of asbestos that make it poisonous. Explain what s unique about exposure to asbestos. Demonstrate some of the difficulties and pitfalls of asbestos exposure measurement.

24

25 Effect of increasing microscope magnification 2,000X Mag. 12X Mag. 10,000X Mag. 200X Mag.

26 PLM Microscope

27 PLM Photo of Tremolite National Enforcement Investigations Center

28 National Enforcement Investigations Center PLM of Amosite and Human Hair

29

30 Air filters may influence exposure measurements Mixed Cellulose Ester Filters may underestimate Asbestos exposure. Nucleopore filters show better Precision and accuracy for asbestos Measurement.

31 Ref: USGS Bundle of Libby amphibole asbestos fibrils

32 Tremolite asbestiform fibrils are born from crystalline growth of mineral-rich solution. Tremolite Asbestos

33 How do cleavage fragments form? X-ray diffraction pattern showing amphibole cleavage planes.

34 Fiber dose increases in the lungs of rats exposed to asbestos Short thin fibers Cook et al (1982) Toxicol. Let 13 (3-4)

35 Need to understand fiber size distributions and associated surface area.

36 Based on LA structures counted by ISO (N = 6247) DB download: 8/3/03 Libby Fiber Size Distribution % of total %-20.0% 16.0%-18.0% %-16.0% %-14.0% Length %-12.0% 8.0%-10.0% %-8.0% 4.0%-6.0% %-4.0% %-2.0% Width

37 % of total Based on LA structures counted by ISO (N = 6247) DB download: 8/3/03 Libby Fiber Size Distribution 20% 18% 16% 14% 12% 10% 8% 6% 4% 2% 0% Width Length

38 Summary Source Exposure Dose Effects Respiration Translocation Clearance Dissolution Oxidation Fiber splitting Epidemiology Toxicology Inhalation rate Measurement error Fate-Transport Dose-Response Relative Potency Figure: A conceptual model for asbestos exposure and response is important for thorough evaluation of asbestos risks. Careful, coordinated data collection for each component of the conceptual model is essential for accurate risk estimates.

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