OEL
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This document discusses occupational cancers and preventive strategies. It defines how carcinogens are identified and classified differently across countries. Approximately 2-8% of cancers are related to occupations, with certain chemicals and industries linked to increased risks of specific cancer types. Biomarkers can help assess exposure to known carcinogens like tobacco smoke and aflatoxin. The International Agency for Research on Cancer (IARC) classifies agents as Group 1 (carcinogenic to humans), Group 2A (probably carcinogenic), Group 2B (possibly carcinogenic) or Group 3 (unclassifiable) based on evidence from human and animal studies. Preventive measures include banning known carcinogens from industry and replacing them with safer substitutes when possible
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- 1. Occupational Cancers and Preventive Strategies Dr. Manish Singhal MD, DM (AIIMS), ECMO (Gold Medal) European Certified Medical Oncologist Ex. Committee Member - Ind. Soc of Med & Ped Oncology (ISMPO) Jt. Sec NCR Oncology Forum Senior Consultant Medical Oncology Dharamshila Hospital and Research Center New Delhi
- 2. DEFINING OF CARCINOGENS The control of occupational carcinogenic substance is exercised by scientific researches on human beings and experimental modeling systems. It differs from some countries to other's because of differences in legislative implementations. For example, a certain chemical was defined as carcinogen in Finland, after a while Denmark marked it as carcinogen. In this period ACGIH(American Conference of Industrial Hygienists) accepted it as suspicious carcinogen.
- 3. HOW MUCH ARE CANCERS RELATED TO OCCUPATIONS? 2-8% (1981 Doll &Peto) Every year 25,000-100,000 new case in USA Data is not available in India
- 4. OCCUPATIONAL CANCER First occupational cancer case: Scrotum cancer(1775)- Percival Pott Exposure of chimney sweep to soot Some polycyclic hydrocarbons were defined-1930
- 5. Exposure Exogenous Endogenous Genetic Susceptibility Occupational cancer The extent to which chemical exposures contribute to cancer incidence was not fully appreciated until population-based studies documented differing organ-specific cancer rates of up to 300-fold among geographically distinct populations. Carcinogenesis is a multistage process Behind each stage are numerous genetic events Wide inter-individual variation in response to carcinogen exposure The human response is not homogeneous.
- 6. Virtually every major form of human cancer can be reproduced in experimental animals by exposure to specific chemical carcinogens Animal models have revealed the constancy of carcinogen-host interaction among mammalian species Coal tar Squamous cell carcinomas Vinyl chloride Hepatic angiosarcomas Aflatoxin Hepatocarcinoma Aromatic amines Bladder cancer. Oncogene Tumor Suppressor gene Failure of DNA repair
- 7. The National Toxicology Program lists more than 200 chemical, physical and infectious agents as known or probable environmental carcinogens. Genotoxic Non-Genotoxic Chemical carcinogen Cytochrome P-450 The interaction with DNA is not random: each class of agents reacts selectively with purine and pyrimidine targets DNA Adducts By transfer of alkyl or aryl-alkyl gp -N-nitroso compounds -Aliphatic epoxides - Aflatoxins - Mustards - Polycyclic Aromatic HC - Aryl aromati amines -Aminoazo dyes -Heterocyclic aromatic amines Missense or nonsense mutations macrogenetic damage - chromosome breaks - large deletions Signature Mutation p53 Mechanism? - Toxic cell death - Regenerative hyperplasia - Oxyradical damage - Depurination - Deamination - Hormonal effects Pesticides and herbicide Need long continued exposure Oncogene Tumor Suppressor gene
- 8. Benzene as a Model for Gene-Environment Interaction Benzene exposure is widespread among a number of occupational groups : oil and gas industry, automotive repair, shoe manufacturing, also from cigarette smoke, gasoline, and automobile exhaust. Benzene is linked to hematologic toxicity including aplastic anemia, and acute myeloid leukemia. benzene oxide and hydroquinone Reactive benzoquinones myeloperoxidase covalent binding to DNA alterations in gene expression chromosomal aberrations CYP4502E1 Benzene Liver Bone Marrow Leukemia Functional Polymorphism decreasing activity MPO NAD(P):quinone oxidoreductase Functional Polymorphism decreasing activity Quinone Oreductase
- 9. Target organ Agent Industry Tumor type Lung Tobacco smoke, arsenic, asbestos, crystalline silica, benzo(a)pyrene, beryllium, ether, 1,3-butadiene, chromium compounds, coal tar and pitch, nickel compounds, soots, mustard gas Aluminum production, coal gasification, coke production, hematite- mining, painters Squamous, large cell, and small cell cancer and adenocarcinoma Pluera Asbestos, erionite - Mesothelioma Oral cavity & esophagus Tobacco smoke, alcoholic beverages, nickel compounds Boot and shoe production, furniture manufacturer, isopropyl alcohol production Squamous cell ca Gastric Smoked, salted and pickled foods Rubber Adenocarcinoma Colon Heterocyclic amines, asbestos Pattern maker Adenocarcinoma Liver Aflatoxin, vinyl chloride, tobacco smoke, alcoholic beverages, thorium dioxide - Hepatocellular carcinoma, hemangiosarcoma Kidney Tobacco smoke, phenacetin RCC Bladder Tobacco smoke, 4-aminobiphenyl, benzidine, 2-napthylamine, phenacetin Magenta Manufacturer Transitional cell ca Prostate Cadmium - Adenocarcinoma Skin Arsenic, benzo(a)pyrene, coal tar and pitch, mineral oils, soots, cyclosporin A, PUVA Coal gasification, coke production Sqamous cell ca Basal cell ca Bone Marrow Benzene, tobacco smoke, ethylene oxide, antineoplastic agents, cyclosporin A Rubber workers Oil & petroleum Leukemia and lymphoma
- 10. Physical factors UVC 240 to 290 nm mercury lamps -used for sterilization DNA interactions dimers between adjacent pyrimidines UVB 290 to 320 nm Skin cancer DNA interactions dimers between adjacent pyrimidines UVA 320 to 400 nm Carcinogenic though weakly absorbed by DNA production of reactive oxygen species through its interactions with target chromophores
- 11. Ionizing radiation ATOMIC BOMB Japanese survivors OCCUPATIONAL EXPOSURES Radiologists Underground miners Radium dial painters Nuclear workers Radiation technologists MEDICAL EXPOSURES Ankylosing spondylitis patients Tinea capitis Thymic enlargement Benign breast disease Benign gynecologic disease Fluoroscopy during treatment for tuberculosis Cervical cancer Hodgkin's lymphoma Breast cancer Childhood cancer Mechanism Double stranded DNA breaks Leading to chromosomal instability, mutations and rearrangements At Low dose levels 200mGy additive effect ! Equivalent whether the dose was received all at once or accumulated over a long period of time At Higher dose level 2-3 Gy dose rate reduction factor (DREF). Carcinogenic risks after fractionated exposures are lower than after single acute exposures
- 12. Approximate Mean Doses for Selected Exposures to Ionizing Radiation Exposure Mean Individual Dose (mSv) Round-trip flight, New York to London 0.1 Single screening mammogram (breast dose) 3 Background dose due to natural radiation exposure 3/y Pediatric computed tomography scan (stomach dose from abdominal scan) 25 Radiation worker exposure limit 20/y Exposure on international space station 170/y
- 14. Biomarkers of Cancer Risk External exposure measurements Internal exposure measurements Biomarkers estimating the biologically effective dose Biomarkers of harm - Biomarkers are available to assess N-nitrosamine exposure from tobacco smoke (e.g., urinary tobacco specific nitrosamine levels) - Urinary aflatoxin adduct levels vary among regions of the world, - There are several methods for detecting PAH DNA adducts as well as measuring PAH metabolites in the urine. No single biomarker has been considered to be sufficiently validated for use as a cancer risk marker in an individual
- 15. IARC The International Agency for Research on Cancer (IARC) is part of the World Health Organization. IARC's mission is to coordinate and conduct research on the causes of human cancer, the mechanisms of carcinogenesis, and to develop scientific strategies for cancer prevention and control. The Agency is involved in both epidemiological and laboratory research and disseminates scientific information through publications, meetings, courses, and fellowships.
- 16. The International Agency for Research on Cancer (IARC )CLASSIFICATION Group 1: Carcinogenic to humans Group 2A: Probably carcinogenic to humans Group 2B: Possibly carcinogenic to humans Group 3: Not classifiable as to carcinogenicity to humans Group 4: Probably not carcinogenic to humans
- 17. 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 founding Isopropyl alcohol manufacture (strong-acid process) Tobacco smoking and tobacco smoke
- 18. GROUP 2A: PROBABLY CARCINOGENIC TO HUMANS Agents and groups of agents - Such as Androgenic (anabolic) steroids Lead compounds, inorganic Ultraviolet radiation Diesel engine exhaust - Mixtures 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)
- 19. GROUP 2B: POSSIBLY CARCINOGENIC TO HUMANS Agents and groups of agents 248 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)
- 20. GROUP 3: NOT CLASSIFIABLE AS TO CARCINOGENICITY TO HUMANS Agents and groups of agents - 515 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 (including logging) Paint manufacture (occupational exposure in)
- 21. TAKING MEASURES First of all, the material which is defined as carcinogen should be forbidden in industry. Therefore, a substitute for this material should be researched. If there is a need of working by carcinogens, taking measures of decreasing exposure as minimum is mandatory.
- 22. MEASURES THAT REDUCE EXPOSURE Producing and carrying of carcinogens inside a closed system. Measuring exposures in working atmosphere and workers biological system. Well working ventilation system if happens an emergency. PPE (protective clothing, helmets, goggles, or other garments) Rotation Prohibiting of smoking cigarettes
- 23. MEASURES THAT REDUCE EXPOSURE IMPLEMENTING REGULATION FOR THE PROTECTION OF WORKERS FROM THE RISKS RELATED TO EXPOSURE TO CARCINOGEN AND MUTAGEN SUBSTANCES AT WORK Examination of the environmental or occupational site can be performed by governmental agencies, such as the Occupational Safety and Health Administration (OSHA) or the Environmental Protection Agency (EPA), or by private consultants such as certified industrial hygienists. Air sampling performed with area or personal sampling devices to get results that can lead to estimates of exposure based upon an average eight-hour exposure to see deviation from permissible exposure limits (PELs) Toxins can be measured in air, water, soil, and from surfaces
- 24. Occupational Exposure Limit OEL: the generic term for workplace exposure limits set by specific groups Agent: May be physical, chemical or biological Zero exposure is not usually possible OELs are intended to protect workers at a "safe" level of exposure Many chemicals have no established OEL Use extreme precautions for agents with no safe level Safe levels - Material Safety Data Sheets & Literature
- 26. THANK YOU Chemist are the cleanest people you will ever meet They wash their hands even before they go to the restroom !!!