1. Toxicology Chapter # 8

2. Toxicology Introduction What is Toxicology? What is Toxicology? The History of Toxicology. The History of Toxicology. What is Toxic? What is Toxic? Toxicity and Risk. Toxicity and Risk. 7 Classes of Toxins. 7 Classes of Toxins. Types of Toxins. Types of Toxins. Entry Routes and Their Effects. Entry Routes and Their Effects. Dose-Response Relationships. Dose-Response Relationships. Measuring Toxicity. Measuring Toxicity.

3. Toxicology What is Toxicology? What is Toxicology? Commonly called the study of poisons.Commonly called the study of poisons. Most literature agrees that the common definition is too narrow.Most literature agrees that the common definition is too narrow. Toxicology has evolved into several sub-disciplines:Toxicology has evolved into several sub-disciplines: »Forensic »Clinical »Environmental »Industrial, etc.

4. Toxicology History of Toxicology: History of Toxicology: Early man divided substances into food or poisons.Early man divided substances into food or poisons. Poisons extracted from plants and venoms used.Poisons extracted from plants and venoms used. Ebers papyrus (1500 B.C.) - 1st record of >800 poison recipes including hemlock, aconite, & heavy metals.Ebers papyrus (1500 B.C.) - 1st record of >800 poison recipes including hemlock, aconite, & heavy metals. Middle Ages (300 B.C. - 1300 A.D.) Greeks & Romans credited as advanced societies that knew about & used poisons:Middle Ages (300 B.C. - 1300 A.D.) Greeks & Romans credited as advanced societies that knew about & used poisons: »Hypocrates, Aristotle, Theophrastus, Diosorides Modern Age (1400 A.D. - Now) European & US toxicologists lead:Modern Age (1400 A.D. - Now) European & US toxicologists lead: »Paracelsus, Pott, Orfila

5. Toxicology 7 Classes of Toxins: 7 Classes of Toxins: Asphyxiants:Asphyxiants: »Simple »Chemical n Blood n Tissue n Paralyzers CorrosivesCorrosives IrritantsIrritants

6. Toxicology 7 Classes of Toxins, Continued: 7 Classes of Toxins, Continued: SensitizersSensitizers CarcinogensCarcinogens MutagensMutagens TeratogensTeratogens

7. Toxicology Asphyxiants: Asphyxiants: Simple - displace O 2 so that insufficient concentration for respiration leads to suffocation (e.g., CH 4 & N 2 ). 19.5% O 2 required by OSHA.Simple - displace O 2 so that insufficient concentration for respiration leads to suffocation (e.g., CH 4 & N 2 ). 19.5% O 2 required by OSHA. »Rule of Thumb - a contaminant will deplete O 2 content by 1/5 its concentration.

8. Toxicology Asphyxiants, Continued: Asphyxiants, Continued: Chemical - (toxicity not directly related to O 2 depletion):Chemical - (toxicity not directly related to O 2 depletion): »Blood - biochemically react w/RBC inhibiting O 2 up-take (e.g., CO & C 6 H 5 NH 2 ). »Tissue - carried to tissues by RBC where they react to inhibit O 2 up-take (e.g., HCN). »Paralyzers - react biochemically to depress CNS components that control respiration (e.g., H 2 S & C 2 H 5 OH).

9. Toxicology Corrosives: Corrosives: Destroys tissue by chemically reacting with it.Destroys tissue by chemically reacting with it. Reaction often depletes cells of their water and also causes thermal burns from exothermic reactions w/skin moisture (e.g., HF, HNO 3, H 2 SO 4, etc.).Reaction often depletes cells of their water and also causes thermal burns from exothermic reactions w/skin moisture (e.g., HF, HNO 3, H 2 SO 4, etc.).

10. Toxicology Irritants: Irritants: Exposures cause temp inflammation of mucous membranes, eyes, skin, upper respiratory tract.Exposures cause temp inflammation of mucous membranes, eyes, skin, upper respiratory tract. H2O solubility affects where they react:H2O solubility affects where they react: »High - reacts with 1st moisture encountered eyes, nose, throat. »Moderate - reacts with upper respiratory tract & lungs. »Low - delayed reacts in alveolar region.

11. Toxicology Sensitizers (e.g., TDI &, CHO): Sensitizers (e.g., TDI &, CHO): Cause an allergic-type reaction after repeated &/or extended exposures.Cause an allergic-type reaction after repeated &/or extended exposures. »Allergic reacts commonly includes dermatitis-like conditions - small pimples &/or watery blisters that dont always appear at site of contact. »Allergic reacts can also include itching, tingling &/or pain in joints & extremities and upper respiratory tract irritation. Some chemicals can sensitize people to light.Some chemicals can sensitize people to light. »Once exposed sufficiently, the victim gets sunburned &/or develops rashes more easily. Removal of the patient from future contact with the sensitizer is the only way to prevent future attacks with out drugs.Removal of the patient from future contact with the sensitizer is the only way to prevent future attacks with out drugs.

12. Toxicology Carcinogens: Carcinogens: Cause cancer (uncontrolled growth of abnormal cells) usually over substantial repeated exposures, but possibly after small &/or one-time exposures.Cause cancer (uncontrolled growth of abnormal cells) usually over substantial repeated exposures, but possibly after small &/or one-time exposures. Differ from other toxins because: (1) very small doses can cause cancer; & (2) adverse health effects are usually not recognizable until years have passed.Differ from other toxins because: (1) very small doses can cause cancer; & (2) adverse health effects are usually not recognizable until years have passed. Multiple theories on cancer generation include the one-hit theory - one molecule of a carcinogen causing cancer.Multiple theories on cancer generation include the one-hit theory - one molecule of a carcinogen causing cancer.

13. Toxicology Carcinogens, Continued: Carcinogens, Continued: Example: C 6 H 6, asbestos.Example: C 6 H 6, asbestos. Responders must use the highest level of personal protection when working with a carcinogen.Responders must use the highest level of personal protection when working with a carcinogen. Mutagens: Mutagens: Toxins that impart inheritable changes to the DNA & RNA of exposed persons (e.g., C 6 H 6 & H 2 O 2 ).Toxins that impart inheritable changes to the DNA & RNA of exposed persons (e.g., C 6 H 6 & H 2 O 2 ). Some mutagens can cause cancers, but most result in deformities &/or biochemical deficiencies.Some mutagens can cause cancers, but most result in deformities &/or biochemical deficiencies.

14. Toxicology Teratogens: Teratogens: Toxins that cause birth defects in unborn children.Toxins that cause birth defects in unborn children. Depending on when exposures occur (embryonic or fetal stages), adverse effects can be limb or cognitive deformities (e.g., ionizing radiation).Depending on when exposures occur (embryonic or fetal stages), adverse effects can be limb or cognitive deformities (e.g., ionizing radiation).

15. Toxicology Risk: Important Considerations: Risk: Important Considerations: Describes the chance of an event resulting in an uncontrolled release, exposure, contamination, &/or fire.Describes the chance of an event resulting in an uncontrolled release, exposure, contamination, &/or fire. Is often influenced by local incident site conditions, environmental conditions, and physical & chemical properties of the agent(s).Is often influenced by local incident site conditions, environmental conditions, and physical & chemical properties of the agent(s). Caveat: hazardous materials may fit into 2 or more classes of toxins.Caveat: hazardous materials may fit into 2 or more classes of toxins.

16. Toxicology Risk: Important Considerations, Continued: Risk: Important Considerations, Continued: When responding to a HazMat incident, agent(s) toxicity and the risk of exposure, explosion, reaction, &/or fire it poses must be considered to accurately evaluate the hazard.When responding to a HazMat incident, agent(s) toxicity and the risk of exposure, explosion, reaction, &/or fire it poses must be considered to accurately evaluate the hazard. The risk of the outcomes differ from & are independent of the agents toxicity.The risk of the outcomes differ from & are independent of the agents toxicity. All substances are poisons. The toxicity depends on the dose.All substances are poisons. The toxicity depends on the dose.

17. Toxicology Routes of Entry: Routes of Entry: InhalationInhalation DermalDermal ParenteralParenteral IngestionIngestion

18. Toxicology Inhalation: Inhalation: Lungs are the organ where gas exchange vital to respiration occurs.Lungs are the organ where gas exchange vital to respiration occurs. Large surface area make lungs more susceptible to exposure in comparison to skin.Large surface area make lungs more susceptible to exposure in comparison to skin. Rate of respiration is most important factor because it is directly related to rate of absorption.Rate of respiration is most important factor because it is directly related to rate of absorption.

19. Toxicology Inhalation, Continued: Inhalation, Continued: Toxic Effects of Inhalation:Toxic Effects of Inhalation: »Lung cancer. »Fibrosis - scar tissue that restricts lung capacity (e.g., NH 3 ). »Sensitization - short-term constriction of air ways may develop into long-term pulmonary disease (e.g., TDI & SO 2 ). »Irritation - constriction of airways may lead to infection or edema.

20. Toxicology Dermal Entry: Dermal Entry: Skin is a layer of tissue covering the outer surface of the body:Skin is a layer of tissue covering the outer surface of the body: »Is the largest organ in the human body. »Composed of 3 layers - epidermis, dermis, & subcutaneous. »Is not a protective barrier against hazardous materials. Amount of Toxin Absorbed & Rate Depend on:Amount of Toxin Absorbed & Rate Depend on: »Exposure time. »Skin temperature. »Blood flow at contact site. »Surface area exposed. »Concentration of toxin.

21. Toxicology Dermal Entry, Continued: Dermal Entry, Continued: Toxic Effects of Dermal absorption:Toxic Effects of Dermal absorption: »Irritation resulting in local inflammation &/or rash. »Sensitization resulting in allergic reaction after prolonged or repeated exposure. »Corrosion resulting in chemical & thermal burns that may lead to local disintegration. »Photosensitization resulting in irritation or rash upon exposure to sunlight. »Carcinogenesis resulting in skin cancer.

22. Toxicology Ingestion: Ingestion: »Includes the mouth, pharynx, esophagus, stomach, small intestine, and large intestine »Most common route involves foul play »Least likely route in occupational or environmental exposures »Occurs inadvertently via inhalation clearance mechanisms Toxic Effects of Ingestion:Toxic Effects of Ingestion: »Inflammation of the liver »Cirrhosis - a progressive fibrotic disease »Tumors - liver cancer Other organ systems may be affected or damaged by toxins (e.g., CNS, reproductive, endocrine, etc.)Other organ systems may be affected or damaged by toxins (e.g., CNS, reproductive, endocrine, etc.)

23. Toxicology Dose - Response: Dose - Response: A correlative relationship describing the characteristics of exposure & the spectrum of effects:A correlative relationship describing the characteristics of exposure & the spectrum of effects: »It is assumed that the response is caused by the dose. Accounts for the average response of a population.Accounts for the average response of a population. Biovariability due to sex, age, race, nutrition/health.Biovariability due to sex, age, race, nutrition/health. A Dose-Response Curve graphs the number of deaths on the y-axis & dose on the mantissa.A Dose-Response Curve graphs the number of deaths on the y-axis & dose on the mantissa. Applies to 95% of adult worker population.Applies to 95% of adult worker population.

24. Toxicology Definitions: Definitions: LD 50 - dose at which 50% of the test population dies (mg/Kg). Dose is adjusted for body weight.LD 50 - dose at which 50% of the test population dies (mg/Kg). Dose is adjusted for body weight. LC 50 - airborne concentration at which 50% of the test population dies (ppm). Independent of body weight.LC 50 - airborne concentration at which 50% of the test population dies (ppm). Independent of body weight. LD lo - dose at which the first test subject dies (mg/Kg).LD lo - dose at which the first test subject dies (mg/Kg). NOEL - highest dose or airborne concentration at which no effect is observed.NOEL - highest dose or airborne concentration at which no effect is observed. TLV-TWA - time-weighted average exposure for a conventional 8-hour workday and 40-hour workweek, to which it is believed that nearly all workers may be repeatedly exposed, day after day, without adverse effect.TLV-TWA - time-weighted average exposure for a conventional 8-hour workday and 40-hour workweek, to which it is believed that nearly all workers may be repeatedly exposed, day after day, without adverse effect.

25. Toxicology Definitions, Continued: Definitions, Continued: TLV-C - the concentration that should not be exceeded during any part of the working exposure.TLV-C - the concentration that should not be exceeded during any part of the working exposure. PEL - that time-weighted average concentration to which a normal worker could be exposed for his/her entire working lifetime (30 years of 40-hour workweeks) and not experience material health impairment.PEL - that time-weighted average concentration to which a normal worker could be exposed for his/her entire working lifetime (30 years of 40-hour workweeks) and not experience material health impairment. STEL - a 15-minute TWA exposure which should not be exceeded at any time during a workday, even if the 8-hour TWA is within the TLV-TWA.STEL - a 15-minute TWA exposure which should not be exceeded at any time during a workday, even if the 8-hour TWA is within the TLV-TWA. IDLH - concentration of airborne contaminant which represents the max level from which one could escape w/in 30 minutes, w/out any escape-impairing symptoms or irreversible health effects.IDLH - concentration of airborne contaminant which represents the max level from which one could escape w/in 30 minutes, w/out any escape-impairing symptoms or irreversible health effects.

26. Toxicology Definitions, Continued: Definitions, Continued: MAC - max exposure at any given time (ppm).MAC - max exposure at any given time (ppm). LOC - (IDLH/10) determines the geographic area of risk in the event of chemical release.LOC - (IDLH/10) determines the geographic area of risk in the event of chemical release. ERPG-1 - Max airborne concentration to which nearly all could be exposed for up to 1 hour w/out experiencing health effects more severe than mild irritation or sensory perception.ERPG-1 - Max airborne concentration to which nearly all could be exposed for up to 1 hour w/out experiencing health effects more severe than mild irritation or sensory perception. ERPG-2 - Max airborne concentration below which nearly all could be exposed for up to 1 hour w/out experiencing irreversible adverse health effects or symptoms which could impair an individuals ability to take protective action.ERPG-2 - Max airborne concentration below which nearly all could be exposed for up to 1 hour w/out experiencing irreversible adverse health effects or symptoms which could impair an individuals ability to take protective action. ERPG-3 - Max airborne concentration below which nearly all could be exposed for up to 1 hour w/out experiencing life- threatening health effects.ERPG-3 - Max airborne concentration below which nearly all could be exposed for up to 1 hour w/out experiencing life- threatening health effects.

27. Toxicology SUMMARY What is Toxicology? What is Toxicology? The History of Toxicology. The History of Toxicology. What is Toxic? What is Toxic? Toxicity and Risk. Toxicity and Risk. 7 Classes of Toxins. 7 Classes of Toxins. Types of Toxins. Types of Toxins. Entry Routes and Their Effects. Entry Routes and Their Effects. Dose-Response Relationships. Dose-Response Relationships. Measuring Toxicity. Measuring Toxicity.

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29. Toxicology EXAM TIME