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In the name of God

In the name of God. Occupational carcinogens DR. M . Saraei. Occupational cancer. 2-8%of all human cancers are due to occ. exposure to carcinogens. The most occ. cancers are completely preventable. What is a carcinogen?. A carcinogen is an agent which is responsible for causing cancer.

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In the name of God

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  1. In the name of God Occupational carcinogens DR. M . Saraei

  2. Occupational cancer • 2-8%of all human cancers are due to occ. exposure to carcinogens. • The most occ. cancers are completely preventable.

  3. What is a carcinogen? • A carcinogen is an agent which is responsible for causing cancer. • Carcinogens may be chemical substances; physical agents, such as asbestos dust; or biological agents, such as certain viruses and bacteria • In the workplace, carcinogenic substances may be inhaled, absorbed through the skin or even ingested in some cases

  4. Environmental carcinogens • 80-90% of human cancers are environmental. • 30% of cancer deaths are attributable to tobacco use, 35% to diet and less than 5% each to alcohol, occ. exposure, pollution, radiation and sexual behavior.

  5. What causes cancer?

  6. How big a problem is occ. Cancer? • Mean about 2-8% of cancers associated to work place exposures. • In U.S these would represent 23000-92000 new cases of cancer each year.

  7. Is there a safe level for exposure to carcinogens? • The carcinogen directly affects the cell,there is no safe level of exposure • A safe level of exposure is difficult to define. • Uncertainty about safe levels of exposure to carcinogens has resulted in the principle of keeping exposure. “as low as reasonable achievable “

  8. Can you prevent cancer by reducing a person's exposure to a carcinogen? • In general the higher the exposure a person has to a carcinogen, the more chance they have of developing cancer. • Anything that can be done to reduce a person's exposure to a carcinogen will reduce their chances of developing cancer

  9. Does smoking cause cancer in the workplace? • As well as being a significant cause of cancer in its own right, smoking has been shown to have a synergistic effect with some other carcinogens. • Asbestos and smoking (multiplative) • radon, arsenic, aromatic amines and crystalline silica.

  10. Protecting Employees against Exposure to Carcinogens • Research and testing • Information and training • Exposure control • Elimination • Substitution • Engineering controls • Personal protective equipment

  11. History • 1775: Scrotal cancer ; chimney sweeps • 1895: Bladder cancer; aromatic amines • 1934: Lung cancer; asbestos • 1962: Lung cancer(S.C.C); chloromethylethers • 1974: Liver angiosarcoma; vinyl chloride

  12. CARCINOGENESIS • Stages in tumor development : - Initiation - Promotion - Progression - Metastasis

  13. initiation • Initial stage to result from irreversible change in the genetic material (DNA) of the cell. • This alteration may occur spontaneously or may be caused by factors such as radiation, nickel, asbestos, beryllium, ……

  14. Promotion • Facilitate tumor development (proliferation of the altered cell) • For example: estrogen, high salt, high fat, cigarette smoke, testosterone,….

  15. progression • Involve those change necessary for the development of a malignant tumor. • Progression to malignancy like initiation is triggered by genetic events.

  16. Distinction between initiators & promoters • Initiators -Genotoxic - Carcinogenic alone - Irreversible reaction -Threshold dose -Single exposure may be sufficient to induce cancer

  17. Distinction between initiators & promoters • Promoters -Epigenic -Not Carcinogenic alone -Reversible effect -Threshold probably exist - Repeated exposures required

  18. Latency period • Interval between first exposure to the agent and first clinical manifestation of the tumor. • This length varies from 4-6 years to 40 years.

  19. Methods in assessment of chemical carcinogenicity • Epidemiologic studies. • Experimental studies in animals. • Short-term test. • Molecular biology

  20. EPIDEMIOLOGIC STUDIESCriteria for Causality • STRENGTH – magnitude of relative risk • CONSISTENCY – reported in multiple studies with different circumstances • BIOLOGICAL GRADIENT – dose-response validity • BIOLOGICAL PLAUSIBILITY – reasonable • TEMPORALITY– cause precedes effect

  21. Animal Studies • IARC requirements • Good qualitative predictor • Not-so-good quantitative predictor • Limitations • High dose exposure is needed in order to detect significance • Different metabolism • Different routes of administration

  22. Short - Term Tests • Provide evidence of mutagenicity • Ames test, sister-chromatin exchange, DNA repair • Quicker results, less expensive • Correlation of results with animals/humans imperfect

  23. Molecular Biology • Allows assessment of exposure and possible early health effects: • Measure enzyme activity of the cytochrome P450 monooxygenase class • Measurement of DNA or Protein adducts • Measurement of protein products in the urine and serum

  24. IARC classification of carcinogens Class I: Human carcinogen based on sufficient positive evidence (beryllium, cadmium, strong inorganic acid mist containing sulfuric acid). Class II: Sufficient animal evidence but limited or inadequate human evidence (probable or possible carcinogens). Ex: acrylonitrile, benzidine, MMVF. Class III: Agents that are not classified. Class IV: Agents that are probably not carcinogen to humans.

  25. GROUP 1: CARCINOGENIC TO HUMANS Agents and groups of agents Such as: Arsenic and arsenic compounds Asbestos Benzene Cadmium and cadmium compounds Formaldehyde Coal-tar pitches -Mixtures Soots Tobacco, smokeless Wood dust… Exposure circumstances: Boot and shoe manufacture and repair Chimney sweeping Iron and steel foundring Isopropyl alcohol manufacture (strong-acid process) Tobacco smoking and tobacco smoke

  26. GROUP 2A: PROBABLY CARCINOGENIC TO HUMANS Agents and groups of agents Such as: Androgenic (anabolic) steroids Lead compounds( inorganic) Ultraviolet radiation Diesel engine exhaust High-temperature frying( emissions) Non-arsenical insecticides… Exposure circumstances: Art glass, glass containers and pressed ware (manufacture of) Carbon electrode manufacture Cobalt metal with tungsten carbide Hairdresser or barber (occupational exposure as a) Petroleum refining (occupational exposures in) Shiftwork that involves circadian disruption Sunlamps and sunbeds (use of)

  27. GROUP 2B: POSSIBLY CARCINOGENIC TO HUMANS Agents and groups of agents Acetaldehyde Chloroform Cobalt and cobalt compounds DDT Magnetic fields (extremely low-frequency) Naphthalene Nickel, metallic and alloys Coffee -Mixtures Engine exhaust, gasoline Fuel oils, residual (heavy) Welding fumes … Exposure circumstances: Carpentry and joinery Cobalt metal without tungsten carbide Dry cleaning (occupational exposures in) Printing processes (occupational exposures in) Textile manufacturing industry (work in)

  28. GROUP 3: NOT CLASSIFIABLE AS TO CARCINOGENICITY TO HUMANS Agents and groups of agents Caffeine Cholesterol Coal dust Ethylene Mercury and inorganic mercury compounds Talc Mineral oils, highly-refined - Mixtures Petroleum solvents Printing inks Tea… Exposure circumstances: Flat-glass and specialty glass (manufacture of) Hair colouring products (personal use of) Leather goods manufacture Lumber and sawmill industries Paint manufacture (occupational exposure in)

  29. GROUP 4: PROBABLY NOT CARCINOGENIC TO HUMANS This list contains all agents evaluated as being in Group 4 to date.

  30. بیماری هایی قابل غربالگری هستند که: -  سیر بیماری کاملا شناخته شده باشد. -  بیماری، مرحله نهفته طولانی داشته باشد. -  در مرحله نهفته، درمان موثر داشته باشد. -  بار بیماری در جامعه قابل توجه باشد.( بیماری، شایع باشد) -  بیماری، موربیدیتی و مورتالیتی قابل توجه داشته باشد. -  تستها و آزمایشاتی که جهت انجام غربالگری آن بیماری ها بکار می روند باید مناسب باشند.

  31. تستها و آزمایشاتی که جهت انجام غربالگری بیماری ها بکار می روند باید شرایط و معیارهایی به شرح زیر داشته باشند: 1- بتوانند بیماری را در مرحله نهفته و قابل برگشت و قابل علاج کشف کند. 2- حساسیت و ویژگی بالا داشته باشد. 3- در دسترس و ارزان باشد. 4- بیمار پذیرش انجام آن را داشته باشد. 5- مبتنی بر شواهد علمی و دقیق باشد. 

  32. Occupations at risk of lung cancer • Asbestos(A. miners, insulation and filter material production, shipyard workers) • Radon(Uranium mining, domestic exposure) • CME (chemical production workers) • PAHs(Rubber workers, roofers, Al. reduction workers) • Chromium (chromate production). • Nickel (mining) • Arsenic(arsenical pesticide production and use, copper, lead, zinc smelting)

  33. Clinical presentations • Constitutional symptoms • Primary Tumor • Intrathoracic spread • Asymptomatic • Extrathoracic spread • Paraneoplastic symptoms

  34. Asymptomatic(10%)

  35. Primary Tumor (30%) • Cough (75%) • SOB (60%) • Chest discomfort (50%) • Hemoptysis (35%)

  36. Cough - endobronchial mass or post-obstructive pneumonia –esp concerned if new onset/changed character • SOB –tumor occluding the airway • Chest discomfort–intermittent/aching • Hemoptysis-acute bronchitis is the common cause of hemoptysis, lung CA should always be suspected in pts >40

  37. Intrathoracic Spread(40%) • Recurrent laryngeal nerve paralysis • Phrenic nerve paralysis • Pancoast’s tumor • Horner Syndrome • Chest wall invasion • Pleural effusion • Esophageal compression • Superior vena cava obstruction

  38. Extrathoracic Spread(30%) • Bone metastasis • bone pain, fracture • Brain mets focal neurol deficits, seizures, confusion, personality change • Liver mets • Adrenal gland mets • Spinal cord mets

  39. Comments • Quitting tobacco use, or not starting at all • Take protective measures against cancer-causing chemicals at work

  40. Mesothelioma • Asbestos: • Asbestos miners. • Insulation and filter material production. • Construction workers. • Roofers. • Shipyard workers.

  41. Cancer of the Nasal cavity & Sinuses • Wood and other dusts • Furniture workers • Boot and shoe manufacturing • Nickel - Nickel refinery worker • Chromium - Chromate pigment manufacture • Isopropyl alcohol, formaldehyde • Laboratory workers • Other industry

  42. Cancer of the Larynx • Asbestos -asbestos miners -insulation and filter material production. -shipyard workers • Cigarette smoking and alcohol abuse are the primary etiologic factors. • Mustard gas • Cutting oil • Nickel • Wood dust • Isopropyl alcohol

  43. Bladder cancer • Naphthylamine - Textile workers( dye/pigment manufacturing) • Benzidine (pigment manufacturing ) • Toludine (painters) • Benzidine- derived azo dyes -Chemical workers • Phenacetin- containing compounds - petroleum workers. -Hairdressers.

  44. Hematologic Cancers • Ionizing radiation • Benzene • Ethylene oxide • Agricultural work • Cytotoxic drugs

  45. Liver • Hepatitis B&C, alcohol, aflatoxins • Solvents associated with hepatic fibrosis • Hepatic Angiosarcoma • Vinyl chloride • Thorotrast • Arsenic

  46. Skin cancer • UV radiation -Outdoor workers. • PAHs -pigment industry workers. -Coal tar workers (fuel production) • Arsenic -Arsenical pesticide production and use. -Copper, lead, zinc smelting. • Ionizing radiation -Uranium miners. -Health workers.

  47. Actinic keratosis • A pre-cancerous condition of thick, scaly patches of sun-damaged skin. Also referred to as solar or senile keratosis.

  48. Basal Cell Carcinoma Three common presentations: Small, smooth, pale, or waxy shiny lump A lump that bleeds or develops a crust Firm, red lump

  49. Similar in appearance to actinic keratosis and basal cell carcinoma. Squamous Cell Carcinoma

  50. Melanoma (the A-B-C and Ds) Asymmetry -- The shape of one half does not match the other.

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