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Sandler Occupational Medicine Associates © 2008 Occupational Respiratory Concerns in the New Millennium Howard M. Sandler, M.D. Sandler Occupational Medicine.

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Presentation on theme: "Sandler Occupational Medicine Associates © 2008 Occupational Respiratory Concerns in the New Millennium Howard M. Sandler, M.D. Sandler Occupational Medicine."— Presentation transcript:

1 Sandler Occupational Medicine Associates © 2008 Occupational Respiratory Concerns in the New Millennium Howard M. Sandler, M.D. Sandler Occupational Medicine Associates, Inc. January 07, 2008

2 Sandler Occupational Medicine Associates © 2008 Body Organ Systems Affected by Occupational Exposures Skin Respiratory Central Nervous System, PNS Liver Kidney Endocrine Reproductive Cardiovascular Gastrointestinal

3 Sandler Occupational Medicine Associates © 2008 HUMAN RESPIRATORY SYSTEM

4 Sandler Occupational Medicine Associates © 2008 Range of Occupational Lung Disorders Asthma (RAD) RADS Lung Cancer Hypersensitivity Pneumonitis Chemical Pneumonitis Bronchiolitis Obliterans (BO) / BOS COPD Interstitial Lung Disease Chronic Cough World Trade Center Lung Infectious Diseases Spread in the Workplace

5 Sandler Occupational Medicine Associates © 2008 Toxicology Aspects in Respiratory Disease Vapor Particle Absorbed Substance Size Matters Dose – Response Distribution Metabolism Latency Specificity of Effect

6 Sandler Occupational Medicine Associates © 2008 Deposition in Respiratory Tract Particle Size (  m) > 15  m  m 5-10  m <5  m Location Outer Portion Nasal Passage Nasal Turbirates, Pharynx Considered INHALED – Major Airways Trachea, Major Stem Bronchi Considered RESPIRABLE – Terminal Bronchioles, Alveoli

7 Sandler Occupational Medicine Associates © 2008 Are There Thresholds for all Adverse Health Effects? Acute effects – odor related symptoms Chronic effects – subtle neurocognitive effects Mutagenicity Carcinogenicity Immunotoxicity Genotoxicity

8 Sandler Occupational Medicine Associates © 2008 HEALTH EFFECT EXPOSURE LEVEL LOW DOSE EXPERIMENTS THRESHOLD

9 Sandler Occupational Medicine Associates © 2008 Selected Odor Recognition Thresholds (PPM) Lowest ReportedOT TLV PEL Formaldehyde 0.27 ppm.75 ppm Hydrogen Sulfide Gas ppm 10 ppm Methyl Ethyl Gas.25 ppm 200 ppm Toluene (Petroleum).021 ppm 50 ppm Trichloroethylene.05 ppm 50 ppm

10 Sandler Occupational Medicine Associates © 2008 Sound Science for General Causal Inference Structure Analogy In Vitro Studies (Ames Test) Animal Studies (Species to Species, Dosing) Pharmacokinetics Epidemiological Approaches Conducting An Experiment

11 Sandler Occupational Medicine Associates © 2008 Reactive Airway Disease (RAD) 2-15% of general population % - Attributable to workplace 2 - 4% of all workers Reversible disease of the pulmonary airways Chronic asthma

12 Sandler Occupational Medicine Associates © 2008 Reactive Airway Disease (RAD) Increasing frequency Increasing severity Age-related incidence Correlation with neurobehavioral disorders

13 Sandler Occupational Medicine Associates © 2008

14 Age (years) PREVELANCE % RAD Prevalence

15 Sandler Occupational Medicine Associates © 2008 Reactive Airway Disease (RAD) Allergic Asthma RADS Non-Specific Triggers

16 Sandler Occupational Medicine Associates © 2008 RAD Associated Conditions Rhinitis Sinusitis Nasal Polyposis Atopic Dermatitis GERD (also causes IPF)

17 Sandler Occupational Medicine Associates © 2008 OBESITY COST FACTORS Total Annual Direct Medical Costs - $75-$100B Total Annual Costs to Business - ??? Weight reduction reduces risk factors and costs for care for these obesity-related conditions: ConditionAnnual U.S. Medical Cost % of Cost Attributable to Obsesity Hypertension$ 1.6 billion17% Type 2 Diabetes$ 2.4 billion61% Coronary Heart Disease$ 2.3 billion17% Gallbladder Disease$ 705 million30% Osteoarhritis$ 57 million24% Others Not SpecifiedSleep ApneaGERD/Asthma Source: Watson Wyatt Worldwide Cancer (Endometrial, Breast and Colon) Stroke

18 Sandler Occupational Medicine Associates © 2008 Occupations that Can Carry Risk of Occupational Asthma Industry/OccupationAgent(s)Potential Exposure Animal breeding/handlingAnimal Antigens2,000,000 BakingFlour, insects, mite debris230,000 HairdresserSodium/potassium persulfate 13,500 Coffee processorGreen coffee beans12,900 Detergent enzyme workerProteases5,700 Farm workersAnimal antigens, vegetable dusts 4,500,000 Food additive workerTartrazine14,000 Grain handlerGrain, insect debris dust97,000 Laboratory workerAnimal antigens11,000 Chromium salts2,000

19 Sandler Occupational Medicine Associates © 2008 Occupations that Can Carry Risk of Occupational Asthma (Cont’d) Industry/OccupationAgent(s)Potential Exposure Lumber & woodworkingWood dusts1,646,000 MillingFlour, insects, mite debris16,000 Paper products manufacturer Natural glues130,000 Pharmaceutical workerPenicillin, ampicillin8,000 Plastics industryDisocynates (TDI, HDI, MDI) 11,500 Anhydrides (PA, TCPA)4,020 Diethylene tri& tetramine5,100 Platinum refinerPlatinum salts300 PrinterVegetable gums6,000

20 Sandler Occupational Medicine Associates © 2008 Bronchiolitis Obliterans Fibrotic Process affecting small airways Interstitium usually spared Clinical picture of fixed airway disease – Severe COPD (restrictive, mixed) Proliferative (BOOP), Constrictive (Concentrically Scarred/Stenotic Airways) Dx – History, PE, PFTs, CXR, HRCT, Bx Sx – Gradual/progressive/acute cough, SOB, fever, night sweats, weight loss

21 Sandler Occupational Medicine Associates © 2008 Bronchiolitis Obliterans (Cont’d) CXR – usually normal (possible hyperinflation) PFTs – Decreased FEV1, increased lung volumes, normal diffusion capacity/some decreased FVC/minimal changes HRCT – air trapping, thickened airway walls, haziness Biopsy – Open v Transbronchial, narrowing or complete destruction of airways (chronic inflammation and fibrosis) CT/HRCT findings in BO similar to those in asthma

22 Sandler Occupational Medicine Associates © 2008 Clinical Syndromes Associated with Histologic Bronchiolitis, with or without Obliterans Inhalation Injury Toxic fume inhalation Irritant gases Mineral dusts Organic dusts Volatile flavoring agents Postinfectious Diffuse lesions Localized lesions Drug-induced reactions

23 Sandler Occupational Medicine Associates © 2008 Clinical Syndromes Associated with Histologic Bronchiolitis, with or without Obliterans (Cont’d) Idiopathic No associated diseases Cryptogenic bronchiolitis Respiratory bronchiolitis-associated interstitial lung disease Cryptogenic organizing pneumonia Associated with other diseases Associated with organ transplantation Associated with connective tissue disease

24 Sandler Occupational Medicine Associates © 2008 Food Flavorings Approximately 1,037 possible respiratory hazard flavorings Aldehydes, ketones, acids, thiols, sulfides

25 Sandler Occupational Medicine Associates © 2008 Flavoring Substances with OSHA PELs And/Or NIOSH RELs Substance: Acetaldehyde Acetic Acid Isoamyl Acetate Isoamyl Alcohol 2-Butanone Butyl Acetate Isobutyl Acetate Butyl Alcohol Isobutyl Alcohol Butylated Hydroxytolene Butyl Lactate Ethyl Acetate Ethyl Acrylate Ethyl Alcohol Ethyl Formate Formic Acid Furfural Furfuyl Alcohol Glycerol

26 Sandler Occupational Medicine Associates © 2008 Flavoring Substances with OSHA PELs And/Or NIOSH RELs (Cont’d) Substance: 2-Heptanone 4-Heptanone Methyl Mercaptan 4-Methyl-2-Pentanone Propionic Acid Propyl Acetate Isopropyl Acetate Propyl Alcohol Isopropyl Alcohol Pyridine Valeraldehyde Phenol Styrene Trimethylamine Acetone 4-Methyl-3-Penten-2-one 1- Butanethiol 2,6-Dimethyl-4-Heptanone Resorcinol

27 Sandler Occupational Medicine Associates © 2008 Flavoring Substances with OSHA PELs And/Or NIOSH RELs (Cont’d) Substance: Isophorone Benzenethiol Diphenyl Ether Hydrogen Sulfide Cyclohexanone 2-Methylcyclohexanone

28 Sandler Occupational Medicine Associates © 2008 Diacetyl (2,3- Butanediol) C4H6O2 Yellowish liquid Odor – strong; rancid, chlorine-like Odor threshold ppb Vapor pressure – 56.8 mm Hg at 25 deg C Naturally occurring substance found in food tobacco smoke contaminant No PEL, REL, TLV, etc

29 Sandler Occupational Medicine Associates © 2008 Microwave Pop-Corn Processing – Missouri Plant 8 workers with BO (ages 29 – 53) Equal gender distribution Latency – 0.5 – 5 years One smoker (protective factor?)

30 Sandler Occupational Medicine Associates © 2008 Conclusions There are numerous substances and conditions (e.g., heating) involved in the manufacture of MW pop-corn; specifically various particulates (oil/grease and salt) and numerous volatile organic compounds (over 100 VOCs) have been identified by the lead governmental agency, NIOSH in this research effort (Kullman, 2005) It is unclear whether diacetyl is the actual etiologic agent in whole or, part or is simply an indicator of exposure (OSHA, 2003; Harber, 2006; Hubbs, 2002)

31 Sandler Occupational Medicine Associates © 2008 Conclusions (Cont’d) Kreiss, 2007 – Review, Causation? Egilman, 2007 – Industry Conspiracy, NO Threshold Schlesinger, 1998 – Critical Review for BO Risk Factors – Flavorings/Diacetyl not Identified Dr. Cecile Rose – National Jewish Medical and Research Center, Denver –“Prior” Consultant to Flavorings Industry (FEMA) – July 18, 2007 Letter to FDA – Consumer with BO and Hx of Making Several Bags of Extra Butter Flavored MW Popcorn for Several Years – Found Similar Diacetyl Airborne Levels to Those Reported in QA Unit of Popcorn Manufacturing Plant

32 Sandler Occupational Medicine Associates © 2008 International Labor Office (ILO) 1980 Pneumoconiosis Classification

33 Sandler Occupational Medicine Associates © 2008 Silicosis & Asbestosis Deaths in the U.S. by Year Silicosis Asbestosis

34 Sandler Occupational Medicine Associates © 2008 Age-Adjusted All Pneumoconiosis Mortality Rates by County US Residents age 15 and over,

35 Sandler Occupational Medicine Associates © 2008 Age-Adjusted Silicosis Mortality Rates by County US Residents age 15 and over,

36 Sandler Occupational Medicine Associates © 2008 Exposure, Morbidity and Mortality Silicosis Risk –1 – 95% of Workers at OSHA PEL Over –40 – 45 Years Working Lifetime –1 – 7% at ½ NIOSH REL – mg/m 3 –20% Increased Risk at 0.04 mg/m 3 for 45 Years –Current Prevalence Unknown –300 Deaths Per Year

37 Sandler Occupational Medicine Associates © 2008 SOMA Exposure and EPI Study 6,000 Cohort, Stone/Gravel/Mining Long-term – Morbidity (Various Endpoints Exposure Modeling Precision Confounding Control Objectives –Dose-response Refinement –Health Effects Non-Silicosis –Disease Progression

38 Sandler Occupational Medicine Associates © 2008 Overall Silica Sampling Results Respirable Silica (mg/m 3 ) YearNo. of samples Reported OEs MeanRange> REL (0.05)> PEL (~0.1) (6%) – (11%)17 (5%) (4%) – (7%)13 (3%) (2%) – (6%)10 (2%) (4%) – (9%)36 (3%) (4%) – (8%)44 (4%) (3%) – (6%)25 (3%) (5%) – (9%)37 (3%) Overall (4%) – (8%)194 (3%)

39 Sandler Occupational Medicine Associates © 2008 Percentage Over PEL / TLV

40 Sandler Occupational Medicine Associates © 2008 Silicosis by Division

41 Sandler Occupational Medicine Associates © 2008 Aggregate FEV 1 Data

42 Sandler Occupational Medicine Associates © 2008 Biomarkers Biological Molecules Used as a Marker of the Substance or Process of Interest –Chromosomal aberrations –Actual substance in blood, urine, etc. –Metabolite –Mutations –Imaging studies (MRI, PET, SPECT)

43 Sandler Occupational Medicine Associates © 2008 “Cytogenetics” What is cytogenetics? What are cytogenetic “markers” and are they useful in occupational and environmental health evaluation? Cytogenetics and exposure specificity Cytogenetics and the carcinogenisis “cascade” Cytogenetics and risk of disease

44 Sandler Occupational Medicine Associates © 2008

45 Diesel Sampling Information

46 Sandler Occupational Medicine Associates © 2008 [Source: Royal Academy of Engineering, Nanoscience and nanotechnologies, July 2004]

47 Sandler Occupational Medicine Associates © 2008 Ultrafine vs. Nanoparticles Both are particles <100 nm Ultrafine – occur either naturally or unintentionally –Welding fumes –Diesel exhaust –Volcanoes –WTC dust Nanoparticle – engineered on purpose

48 Sandler Occupational Medicine Associates © 2008 Quantum Effects The reduced size of nanoparticles results in property changes, in comparison to the bulk material: –Electrical –Mechanical –Chemical –Optical TiO 2 microspheres from sunscreen

49 Sandler Occupational Medicine Associates © 2008 Nano-Consumer Products According to the Andrew Maynard Wilson Center for Scholars, as of November 2006, >350 consumer products and/or product lines contain some nanotechnology

50 Sandler Occupational Medicine Associates © 2008 Nanoparticles and Health Effects Questionable Inflammation in Animals No Known Human Health Effects Hard to Study in Humans, Multiple Exposure Parameters Extrapolation Form WTC Data?

51 Sandler Occupational Medicine Associates © 2008 Thank You For Your Interest “We invite you to visit our newly designed website at


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