Industrial Safety Series Toxicology in the workplace Dr. Ir. Yulianto S Nugroho, MSc. Department of Mechanical Engineering University of Indonesia
Outline of talk Introduction Route of Body Entry Dose-response relationship Acute and chronic effect Air-contaminate exposure Neoplasms Permissible exposure limits Problems 2 Reference : Charles A. Wentz, Safety, Health and Environmental Protection, MGH, 1998.
Introduction Toxicology is the study of the adverse effects of chemicals on living organisms. The science of toxicology is concerned mainly with the toxic or poisonous properties of chemical substances. At sufficiently high concentrations and levels of exposure, all chemicals have the potential of being a hazard. But, at sufficiently low concentration and level of exposure, all chemicals are safe and do not have the potential of being a hazard. Vaccine ampoules Medication, vaccines, and chemical exposure can result in side effects that are life-threatening. The benefit of medicines must be weighted against their adverse effects. 3 3
Introduction (cont) The main objectives of toxicology is to define how much is unacceptable and to recommend precautionary measures and constraints to assure that under normal workplace conditions employees are not exposed to those unacceptable levels. Main factors contribute to toxicity: Route of entry Dosage level Physiological state of the receiver Environmental conditions Pharmaceutical samples Physical properties of the chemical Chemical properties of the chemical 4 4
Route of body entry The route of entry into the body plays an important role in chemical toxicity. The toxic effects of a substance are dependent upon how it gains entrance into the body and, further, into the bloodstream. The most common routes of entry into the body are inhalation, absorption through the skin, ingestion, and injection. A substance can enter via more than one route at a time, depending upon the chemical properties and surrounding conditions (i.e. by both inhalation and skin absorption). 5 5 Intravenous feeding bag Once the chemical has entered the bloodstream, the toxic effect may be general or specific to certain organs or tissue.
Route of body entry (cont) When air and its contaminates are inhaled, they first pass through the upper respiratory tract: the nose, throat, trachea, and bronchial tubes. The major parts of the human respiratory system. 6 6
Route of body entry (cont) The air is transported to the alveoli, where the gases are diffused across thin membrane cells walls. 7 7 The gas exchange of air in an alveolus.
Route of body entry (cont) This gas diffusion model is based mainly upon the differential partial pressures of oxygen and carbon dioxide in the respiratory system. Gas diffusion model for the respiratory system and the bloodstream. 8 8
Route of body entry (cont) The oxygen concentration in the bloodstream is greater than in the tissue cells, causing oxygen to permeate the capillary walls to increase the level of oxygen in the tissue cells. Gas diffusion model for the bloodstream and tissue cells. 9 9 Oxygen deficiency for normal adults: 21% to 15% : no immediate effects 15% to 10% : dizziness and breathless 7% to 5% : life-threatening conditions < 5% : death in minutes. Possible outcomes when a chemical in contact with skin: The skin may block entry into the body The chemical may cause skin irritation It may produce skin sensitization It may penetrate the skin and enter the bloodstream.
Dose-response relationship Test Tubes Test Tubes 10 The dose-response relationship is the basis for toxicological considerations. A dose of a chemical is administered to a test animal species and the outcome is observed. This methodology is continued by trial and error until a range is identified where all or most of the test animals die at one end and all or most of the test animals survive at the other end of the range.
Dose-response relationship (cont) The data from the specific test conditions are plotted to form a typical relation as shown on the left. Dosage levels are reported as: Quantity per unit of body weight Quantity per unit of air volume respired Quantity per unit of exposed skin surface The length of time of exposure is also critical to the dose-response relationship. Typical dose-response relationship. When the chemical concentration and the exposure time are considered together, their product becomes an important criterion, since high concentrations for short time periods produce similar effects a s low concentrations over longer time frames. 11 11
Dose-response relationship (cont) Chemical LD 50 Ethyl alcohol 10,000.00000 Sodium cloride 4,000.00000 Ferrous sulfate 1,500.00000 Strychnine sulfate 2.00000 Nicotine 1.00000 2,3,7,8 tetrachlorodibenzo-p-dioxin 0.00100 Botilinus toxin 0.00001 The dose-response curve can be used to study the lethal dose (LD) in the test animal population. LD 50 is the dose of a substance that will be fatal to 50% of a defined animal population. 12 LD 0 and LD 100 refer to 0 or 100% fatalities, respectively. The LD units are expresses in mg per kg weight.
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Relative Toxicity Classifications 14
Threshold effect of chemical exposure Since low-level exposures to most chemicals are not harmful, it follows that there is a threshold level below which there is no effect or a potentially beneficial effect. 15 As shown above, as dose is increased, there is a point that begins to produce a measurable adverse effect. This initial toxicity observation and the rate of increasingly adverse effect are used to define the degree of toxicity of a substance.
Acute and Chronic effects ACUTE : Acute exposures and effects are short-term at high concentrations with almost immediate results. Acute exposures usually last less than 24 hours and are often related to an accident. CHRONIC : Chronic effects have symptoms of illness of long duration or frequent recurrence. The chronic effects develop slowly over a long period of time. Green Laser The symptoms of chronic poisoning occur at low levels of contaminant and are not apparent for a long time period-years or even decades of exposure. 16 16
Air-contaminate exposure Inhalation of air contaminates is the most common exposure route for toxic chemicals in the workplace. It can be classified into : irritants, asphyxiants and narcotics. Irritant causes aggravation upon contact with tissue, Asphyxiants block or otherwise interfere with the transfer of oxygen to body tissue and will result in suffocation. Air pollution caused by forest fires Narcotics interfere with the central nervous system by causing anesthesia, the loss of sensation. 17 17
Neoplasms Chemical barrels A neoplasms is a new growth of tissue that serves no physiological function. This abnormal tissue growth is often used to describe cancerous or potentially cancerous tissue. 18 A carcinogen is an agent that produces or causes cancer.
Permissible exposure limits The permissible exposure limits for industrial chemical exposure are usually based upon the threshold limit values (TLVs). If the TLV for a substance is exceeded, a person could be harmed. The TLVs are determined for : Gas in ppm and mg/m 3 Particulate in mg/m 3 Conversion : mg/m 3 = ppm (mol wt)/24.5 at 25 o C 19
Permissible exposure limits (cont) 1. TLV, time weighted average: TLV TWA = n i= 1 n t i= 1 i C t i i 2. TLV, short-term-exposure limit: TLV STEL = n i= 1 t i C i 0.25 3. TLV, ceiling: TLV mix = n i= 1 C i TLV i 20
TLV-TWA 21
Problems (homework) 1. Define LD 50 for a chemical substance? 2. Which is more important in industrial toxicology the toxicity of the substance or the risk and hazard associated with its use? 3. What are the major routes by which toxic chemicals gain access to the body? 4. What is the difference between acute and chronic exposure to toxic chemicals? 5. Name some lifestyle factors that cause cancer? 6. Workplace air contains 120 ppm isoproplyl alcohol (TLV, 400 ppm), 0.3 ppm chlorine (TLV, 0.5 ppm) and 45 ppm nitroethane (TLV, 100 ppm). Are combined effects of this mixture in compliance? 22
Problems (homework) 7. In the sixteenth century. Paracelsus, a Swiss alchemist and physician who introduced lead, sulfur, iron, and arsenic into pharmaceutical chemistry said, "All substances are poisons, there is none which is not a poison, the right dose differentiates a poison and remedy." How does his statement relate to the present-day science of toxicology`? 8. Which is more important in industrial toxicology-the toxicity of the substance or the risk or hazard associated with its use. 9. What constitutes an acceptable risk for exposure to a toxic chemical? 10. Name some factors that could be considered in determining an acceptable toxicology risk. 11. What constitutes safe and highly toxic oral chemical-dose levels for humans? 12. What are the major routes by which toxic chemicals gain access to the body? 23
Problems (homework) 13. What route to the body would produce the greatest toxic effect and the most rapid response for a dose of a toxic chemical? 14. A toxic chemical is known to be detoxified in the liver. Would it be more or less toxic if ingested rather than inhaled? 15. Which of the major routes to the body relate more frequently to industrial exposure? 16. What is the difference between acute and chronic exposure to toxic chemicals? 17. Describe the effects of a single benzene exposure as compared to repeated benzene exposures at the same dosage level. 18. In attempting to characterize the toxicity for a specific chemical, would you need acute or chronic exposure information? 19. How does fractionation of the chemical dose relate to the effect of the chemical exposure? 15 Name some known human carcinogens and their adverse effects on humans. 20. What lifestyle factors are known to cause cancer? 24
Problems (homework) 21. Why is the term chemical looked upon unfavorably by society? 22. How does the public perception of risk to chemical exposure differ from that of scientists and engineers? 23. What are carcinogens? 24. Define TLV-TWA, TLV-STEL, and TLV-C for hazardous chemicals. 25. Based on the acute LDSo values in Table 3-2, would you expect nicotine or strychnine sulfate to be more toxic? 26. Name some lifestyle factors that cause cancer. 27. Where can the list of known carcinogens be found? 24 Where can the list of suspected carcinogens be found? 25 Where can the TLV for chemicals be found? 28. What is the concentration in mg/m; of 5 ppm of carbon tetrachloride? 27 What is the concentration in mg/m3 of 25 ppm of ammonia? 29. The 8-hour TWA of airborne acetic acid concentration in the workplace measures 15 ppm. The TLV-TWA measures 10 ppm. Is this location in compliance? 25
Problems (homework) 30. The 8-hour TWA of airborne methyl ethyl ketone (MEK) concentration in the workplace measures 40 ppm. The TLV-TWA measures 200 ppm. Is this location in compliance? 30 Workplace air contains 100 ppm butane (TLV 800 ppm), 50 ppm pentane (TLV 600 ppm) and 10 ppm hexane (TLV 50 ppm). Are the combined effects of this mixture in compliance? 31. Workplace air contains 120 ppm isopropyl alcohol (TLV 400 ppm), 0.3 ppm chlorine (TLV 0.5 ppm), and 45 ppm nitroethane (TLV 100 ppm). Are the combined effects of this mixture in compliance? 32. A liquid contains 40 wt % heptane (TLV 400 ppm), 35 wt % methyl chloroform (TLV 350 ppm) and 25 wt % perchloroethylene (TLV, 25 ppm). Assume the atmospheric composition to be the same as the liquid. What is the TLV of this mixture in mg/m'? 33. What are the main chemical exposure routes in the workplace? 34. What is the key gas or vapor property that determines the rate of uptake from the alveoli into the bloodstream? 26
Problems (homework) 35. What is the target organ for the toxic effects of a narcotic substance? 36. What is the target organ for the toxic effects of chronic mercury exposure? 37. During an 8-hour workday the ammonia levels at a work location were 10 ppm (5 h), 20 ppm (1 h), and 30 ppm (2 h). Is the air level in compliance if the NH3 PEL is 25 ppm? 38 The isopropyl alcohol vapor levels at a workstation during an 8-h workday were 450 ppm (2 h), 375 ppm (3 h), and 385 ppm (3 h). Is this exposure level in compliance if the isopropyl alcohol PEL is 400 ppm? 38. What is the partial pressure of oxygen POZ in air at standard conditions? 39. What adverse skin conditions could be caused by exposure to coal tar chemicals? 40. In lower molecular weight chlorinated aliphatic compounds, what is the TLV effect of increasing the chlorine content? 41. What is the chemical classification of benzene, toluene, and xylene? 27