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Toxicology Chapter # 8. Toxicology Introduction What is Toxicology? What is Toxicology? The History...

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Toxicology Toxicology Chapter # 8
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Page 1: Toxicology Chapter # 8. Toxicology Introduction What is Toxicology? What is Toxicology? The History of Toxicology. The History of Toxicology. What is.

ToxicologyToxicology

Chapter # 8

Page 2: Toxicology Chapter # 8. Toxicology Introduction What is Toxicology? What is Toxicology? The History of Toxicology. The History of Toxicology. What is.

ToxicologyToxicologyIntroductionIntroduction

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.

Page 3: Toxicology Chapter # 8. Toxicology Introduction What is Toxicology? What is Toxicology? The History of Toxicology. The History of Toxicology. What is.

ToxicologyToxicology

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 Most literature agrees that the common definition is too narrow.narrow.

• Toxicology has evolved into several sub-disciplines:Toxicology has evolved into several sub-disciplines:

» ForensicForensic

» ClinicalClinical

» EnvironmentalEnvironmental

» Industrial, etc.Industrial, etc.

Page 4: Toxicology Chapter # 8. Toxicology Introduction What is Toxicology? What is Toxicology? The History of Toxicology. The History of Toxicology. What is.

ToxicologyToxicology

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 Ebers papyrus (1500 B.C.) - 1st record of >800 poison recipes including hemlock, aconite, & heavy metals.including hemlock, aconite, & heavy metals.

• Middle Ages (300 B.C. - 1300 A.D.) Greeks & Romans Middle Ages (300 B.C. - 1300 A.D.) Greeks & Romans credited credited as as advanced societies that knew about & used poisons:advanced societies that knew about & used poisons:

» Hypocrates, Aristotle, Theophrastus, DiosoridesHypocrates, 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, OrfilaParacelsus, Pott, Orfila

Page 5: Toxicology Chapter # 8. Toxicology Introduction What is Toxicology? What is Toxicology? The History of Toxicology. The History of Toxicology. What is.

ToxicologyToxicology

7 Classes of Toxins:7 Classes of Toxins:

• Asphyxiants:Asphyxiants:» SimpleSimple» ChemicalChemical

BloodBlood TissueTissue ParalyzersParalyzers

• CorrosivesCorrosives• IrritantsIrritants

Page 6: Toxicology Chapter # 8. Toxicology Introduction What is Toxicology? What is Toxicology? The History of Toxicology. The History of Toxicology. What is.

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7 Classes of Toxins, 7 Classes of Toxins, ContinuedContinued::

• SensitizersSensitizers• CarcinogensCarcinogens• MutagensMutagens• TeratogensTeratogens

Page 7: Toxicology Chapter # 8. Toxicology Introduction What is Toxicology? What is Toxicology? The History of Toxicology. The History of Toxicology. What is.

ToxicologyToxicology

Asphyxiants:Asphyxiants:

• Simple -Simple - displace O displace O22 so that insufficient so that insufficient

concentration for respiration leads to suffocation concentration for respiration leads to suffocation (e.g., CH(e.g., CH4 4 & N& N22). ). 19.5% O19.5% O22 required by OSHA. required by OSHA.

» Rule of Thumb -Rule of Thumb - a contaminant will deplete O a contaminant will deplete O22

content by 1/5 its concentration.content by 1/5 its concentration.

Page 8: Toxicology Chapter # 8. Toxicology Introduction What is Toxicology? What is Toxicology? The History of Toxicology. The History of Toxicology. What is.

ToxicologyToxicology

Asphyxiants, Asphyxiants, ContinuedContinued::

• Chemical -Chemical - (toxicity not directly related to O (toxicity not directly related to O22

depletion):depletion):

» Blood -Blood - biochemically react w/RBC inhibiting O biochemically react w/RBC inhibiting O22 up-take up-take

(e.g., CO & C(e.g., CO & C66HH55NHNH22).).

» Tissue -Tissue - carried to tissues by RBC where they react to carried to tissues by RBC where they react to inhibit Oinhibit O22 up-take up-take (e.g., HCN).(e.g., HCN).

» Paralyzers -Paralyzers - react biochemically to depress CNS react biochemically to depress CNS components that control respiration components that control respiration (e.g., H(e.g., H22S & CS & C22HH55OH).OH).

Page 9: Toxicology Chapter # 8. Toxicology Introduction What is Toxicology? What is Toxicology? The History of Toxicology. The History of Toxicology. What is.

ToxicologyToxicology

Corrosives:Corrosives:

• Destroys tissue by chemically reacting with Destroys tissue by chemically reacting with it.it.

• Reaction often depletes cells of their water Reaction often depletes cells of their water and also causes thermal burns from and also causes thermal burns from exothermic reactions w/skin moisture (e.g., exothermic reactions w/skin moisture (e.g., HF, HNOHF, HNO33, H, H22SOSO44, etc.)., etc.).

Page 10: Toxicology Chapter # 8. Toxicology Introduction What is Toxicology? What is Toxicology? The History of Toxicology. The History of Toxicology. What is.

ToxicologyToxicology

Irritants:Irritants:

• Exposures cause temp inflammation of mucous Exposures cause temp inflammation of mucous membranes, eyes, skin, upper respiratory tract.membranes, eyes, skin, upper respiratory tract.

• H2O solubility affects where they react:H2O solubility affects where they react:

» High -High - reacts with 1st moisture encountered eyes, reacts with 1st moisture encountered eyes, nose, throat.nose, throat.

» Moderate -Moderate - reacts with upper respiratory tract & reacts with upper respiratory tract & lungs.lungs.

» Low -Low - delayed reacts in alveolar region. delayed reacts in alveolar region.

Page 11: Toxicology Chapter # 8. Toxicology Introduction What is Toxicology? What is Toxicology? The History of Toxicology. The History of Toxicology. What is.

ToxicologyToxicology

Sensitizers Sensitizers (e.g., TDI &, CHO):(e.g., TDI &, CHO):

• Cause an allergic-type reaction afterCause an allergic-type reaction after repeated &/or extended repeated &/or extended exposuresexposures..

» Allergic reacts commonly includes dermatitis-like conditions Allergic reacts commonly includes dermatitis-like conditions - small pimples &/or watery blisters that don’t always - small pimples &/or watery blisters that don’t always appear at site of contact.appear at site of contact.

» Allergic reacts can also include itching, tingling &/or pain in Allergic reacts can also include itching, tingling &/or pain in joints & extremities and upper respiratory tract irritationjoints & 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 Once exposed sufficiently, the victim gets sunburned &/or

develops rashes more easily.develops rashes more easily.• Removal of the patient from future contact with the sensitizer is Removal of the patient from future contact with the sensitizer is

the only way to prevent future attacks with out drugs.the only way to prevent future attacks with out drugs.

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Carcinogens:Carcinogens:

• Cause cancer (uncontrolled growth of abnormal cells) Cause cancer (uncontrolled growth of abnormal cells) usually over substantial repeated exposures, but usually over substantial repeated exposures, but possibly after small &/or one-time exposures.possibly after small &/or one-time exposures.

• Differ from other toxins because: (1) very small doses Differ from other toxins because: (1) very small doses can cause cancer; & (2) adverse health effects are can cause cancer; & (2) adverse health effects are usually not recognizable until years have passed.usually not recognizable until years have passed.

• Multiple theories on cancer generation include the Multiple theories on cancer generation include the one-hit theory - one molecule of a carcinogen causing one-hit theory - one molecule of a carcinogen causing cancer.cancer.

Page 13: Toxicology Chapter # 8. Toxicology Introduction What is Toxicology? What is Toxicology? The History of Toxicology. The History of Toxicology. What is.

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Carcinogens, Continued:Carcinogens, Continued:• Example:Example: CC66HH66, asbestos., asbestos.

• Responders must use the highest level of personal Responders must use the highest level of personal protection when working with a carcinogen.protection when working with a carcinogen.

Mutagens:Mutagens:

• Toxins that impart inheritable changes to the DNA & RNA Toxins that impart inheritable changes to the DNA & RNA of exposed persons (e.g., Cof exposed persons (e.g., C66HH66 & H & H22OO22).).

• Some mutagens can cause cancers, but most result in Some mutagens can cause cancers, but most result in deformities &/or biochemical deficiencies.deformities &/or biochemical deficiencies.

Page 14: Toxicology Chapter # 8. Toxicology Introduction What is Toxicology? What is Toxicology? The History of Toxicology. The History of Toxicology. What is.

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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 Depending on when exposures occur (embryonic or fetal stages), adverse effects can be limb or cognitive fetal stages), adverse effects can be limb or cognitive deformities (e.g., ionizing radiation).deformities (e.g., ionizing radiation).

Page 15: Toxicology Chapter # 8. Toxicology Introduction What is Toxicology? What is Toxicology? The History of Toxicology. The History of Toxicology. What is.

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Risk: Risk: Important ConsiderationsImportant Considerations::

• Describes the chance of an event resulting in an Describes the chance of an event resulting in an uncontrolled release, exposure, contamination, &/or fire.uncontrolled release, exposure, contamination, &/or fire.

• Is often influenced by local incident site conditions, Is often influenced by local incident site conditions, environmental conditions, and physical & chemical environmental conditions, and physical & chemical properties of the agent(s).properties of the agent(s).

• Caveat:Caveat: hazardous materials may fit into 2 or more hazardous materials may fit into 2 or more classes of toxins.classes of toxins.

Page 16: Toxicology Chapter # 8. Toxicology Introduction What is Toxicology? What is Toxicology? The History of Toxicology. The History of Toxicology. What is.

ToxicologyToxicology Risk: Risk: Important Considerations, Continued:Important Considerations, Continued:

• When responding to a HazMat incident, agent(s) When responding to a HazMat incident, agent(s) toxicity and the risk of exposure, explosion, reaction, toxicity and the risk of exposure, explosion, reaction, &/or fire it poses must be considered to accurately &/or fire it poses must be considered to accurately evaluate the hazard.evaluate the hazard.

• The risk of the outcomes differ from & are independent The risk of the outcomes differ from & are independent of the agent’s toxicity.of the agent’s toxicity.

• All substances are poisons. The toxicity depends on the All substances are poisons. The toxicity depends on the dose. dose.

Page 17: Toxicology Chapter # 8. Toxicology Introduction What is Toxicology? What is Toxicology? The History of Toxicology. The History of Toxicology. What is.

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Routes of Entry:Routes of Entry:

• InhalationInhalation• DermalDermal• ParenteralParenteral• IngestionIngestion

Page 18: Toxicology Chapter # 8. Toxicology Introduction What is Toxicology? What is Toxicology? The History of Toxicology. The History of Toxicology. What is.

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Inhalation:Inhalation:

• Lungs are the organ where gas exchange Lungs are the organ where gas exchange vital to respiration occurs.vital to respiration occurs.

• Large surface area make lungs more Large surface area make lungs more susceptible to exposure in comparison to susceptible to exposure in comparison to skin.skin.

• Rate of respiration is most important factor Rate of respiration is most important factor because it is directly related to rate of because it is directly related to rate of absorption.absorption.

Page 19: Toxicology Chapter # 8. Toxicology Introduction What is Toxicology? What is Toxicology? The History of Toxicology. The History of Toxicology. What is.

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Inhalation, Inhalation, ContinuedContinued::

• Toxic Effects of Inhalation:Toxic Effects of Inhalation:

» Lung cancer .Lung cancer .» Fibrosis -Fibrosis - scar tissue that restricts lung capacity scar tissue that restricts lung capacity

(e.g., NH(e.g., NH33).).» Sensitization -Sensitization - short-term constriction of air ways short-term constriction of air ways

may develop into long-term pulmonary disease (e.g., may develop into long-term pulmonary disease (e.g., TDI & SOTDI & SO22).).

» Irritation -Irritation - constriction of airways may lead to constriction of airways may lead to infection or edema.infection or edema.

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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.Is the largest organ in the human body.

» Composed of 3 layers - epidermis, dermis, & subcutaneous.Composed of 3 layers - epidermis, dermis, & subcutaneous.

» Is not a protective barrier against hazardous materials.Is not a protective barrier against hazardous materials.

• Amount of Toxin Absorbed & Rate Depend on:Amount of Toxin Absorbed & Rate Depend on:» Exposure time.Exposure time.

» Skin temperature.Skin temperature.

» Blood flow at contact site.Blood flow at contact site.

» Surface area exposed.Surface area exposed.

» Concentration of toxin.Concentration of toxin.

Page 21: Toxicology Chapter # 8. Toxicology Introduction What is Toxicology? What is Toxicology? The History of Toxicology. The History of Toxicology. What is.

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Dermal Entry, Dermal Entry, Continued:Continued:

• Toxic Effects of Dermal absorption:Toxic Effects of Dermal absorption:

» Irritation resulting in local inflammation &/or rash.Irritation resulting in local inflammation &/or rash.» Sensitization resulting in allergic reaction after prolonged or Sensitization resulting in allergic reaction after prolonged or

repeated exposure.repeated exposure.» Corrosion resulting in chemical & thermal burns that may Corrosion resulting in chemical & thermal burns that may

lead to local disintegration.lead to local disintegration.» Photosensitization resulting in irritation or rash upon Photosensitization resulting in irritation or rash upon

exposure to sunlight.exposure to sunlight.» Carcinogenesis resulting in skin cancer.Carcinogenesis resulting in skin cancer.

Page 22: Toxicology Chapter # 8. Toxicology Introduction What is Toxicology? What is Toxicology? The History of Toxicology. The History of Toxicology. What is.

ToxicologyToxicology Ingestion:Ingestion:

» Includes the mouth, pharynx, esophagus, stomach, small Includes the mouth, pharynx, esophagus, stomach, small intestine, and large intestine intestine, and large intestine

» Most common route involves foul playMost common route involves foul play» Least likely route in occupational or environmental Least likely route in occupational or environmental

exposuresexposures» Occurs inadvertently via inhalation clearance Occurs inadvertently via inhalation clearance

mechanismsmechanisms

• Toxic Effects of Ingestion:Toxic Effects of Ingestion:» Inflammation of the liverInflammation of the liver» Cirrhosis - a progressive fibrotic diseaseCirrhosis - a progressive fibrotic disease» Tumors - liver cancerTumors - liver cancer

• Other organ systems may be affected or damaged by toxins Other organ systems may be affected or damaged by toxins (e.g., CNS, reproductive, endocrine, etc.)(e.g., CNS, reproductive, endocrine, etc.)

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Dose - Response:Dose - Response:

• A correlative relationship describing the characteristics A correlative relationship describing the characteristics of exposure & the spectrum of effects:of exposure & the spectrum of effects:

» It is assumed that the response is caused by the dose.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 A Dose-Response Curve graphs the number of deaths on the y-axis & dose on the mantissa.on the y-axis & dose on the mantissa.

• Applies to 95% of adult worker population.Applies to 95% of adult worker population.

100%

50%

LD50 LD100LDlo

Dose (mg/kg)

Mortality

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Definitions:Definitions:

• LDLD5050 - - dose at which 50% of the test population dies (mg/Kg). dose at which 50% of the test population dies (mg/Kg). Dose is adjusted for body weight. Dose is adjusted for body weight.

• LCLC5050 - - airborne concentration at which 50% of the test population airborne concentration at which 50% of the test population dies (ppm). Independent of body weight.dies (ppm). Independent of body weight.

• LDLDlolo - - dose at which the first test subject dies (mg/Kg). dose at which the first test subject dies (mg/Kg).• NOEL -NOEL - highest dose or airborne concentration at which no effect highest dose or airborne concentration at which no effect

is observed.is observed.• TLV-TWA -TLV-TWA - time-weighted average exposure for a conventional time-weighted average exposure for a conventional

8-hour workday and 40-hour workweek, to which it is believed 8-hour workday and 40-hour workweek, to which it is believed that nearly all workers may be repeatedly exposed, day after day, that nearly all workers may be repeatedly exposed, day after day, without adverse effect.without adverse effect.

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Definitions, Definitions, Continued:Continued:

• TLV-C -TLV-C - the concentration that should not be exceeded during the concentration that should not be exceeded during any part of the working exposure.any part of the working exposure.

• PEL -PEL - that time-weighted average concentration to which a that time-weighted average concentration to which a “normal” worker could be exposed for his/her entire working “normal” worker could be exposed for his/her entire working lifetime (30 years of 40-hour workweeks) and not experience lifetime (30 years of 40-hour workweeks) and not experience material health impairment.material health impairment.

• STEL -STEL - a 15-minute TWA exposure which should not be exceeded a 15-minute TWA exposure which should not be exceeded at any time during a workday, even if the 8-hour TWA is within at any time during a workday, even if the 8-hour TWA is within the TLV-TWA.the TLV-TWA.

• IDLH -IDLH - concentration of airborne contaminant which represents concentration of airborne contaminant which represents the max level from which one could escape w/in 30 minutes, w/out the max level from which one could escape w/in 30 minutes, w/out any escape-impairing symptoms or irreversible health effects.any escape-impairing symptoms or irreversible health effects.

Page 26: Toxicology Chapter # 8. Toxicology Introduction What is Toxicology? What is Toxicology? The History of Toxicology. The History of Toxicology. What is.

ToxicologyToxicology Definitions, Definitions, Continued:Continued:

• MAC -MAC - max exposure at any given time (ppm). max exposure at any given time (ppm).• LOC -LOC - (IDLH/10) determines the geographic area of risk in the (IDLH/10) determines the geographic area of risk in the

event of chemical release.event of chemical release.• ERPG-1 -ERPG-1 - Max airborne concentration to which nearly all could Max airborne concentration to which nearly all could

be exposed for up to 1 hour w/out experiencing health effects be exposed for up to 1 hour w/out experiencing health effects more severe than mild irritation or sensory perception.more severe than mild irritation or sensory perception.

• ERPG-2 -ERPG-2 - Max airborne concentration below which nearly all Max airborne concentration below which nearly all could be exposed for up to 1 hour w/out experiencing irreversible could be exposed for up to 1 hour w/out experiencing irreversible adverse health effects or symptoms which could impair an adverse health effects or symptoms which could impair an individual’s ability to take protective action.individual’s ability to take protective action.

• ERPG-3 -ERPG-3 - Max airborne concentration below which nearly all Max airborne concentration below which nearly all could be exposed for up to 1 hour w/out experiencing life-could be exposed for up to 1 hour w/out experiencing life-threatening health effects.threatening health effects.

Page 27: Toxicology Chapter # 8. Toxicology Introduction What is Toxicology? What is Toxicology? The History of Toxicology. The History of Toxicology. What is.

ToxicologyToxicologySUMMARYSUMMARY

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.

Page 28: Toxicology Chapter # 8. Toxicology Introduction What is Toxicology? What is Toxicology? The History of Toxicology. The History of Toxicology. What is.

QuestionsQuestionsQuestionsQuestions

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1. E-mail question(s) to [email protected]

2. Your question(s) will be answered asap.

Page 29: Toxicology Chapter # 8. Toxicology Introduction What is Toxicology? What is Toxicology? The History of Toxicology. The History of Toxicology. What is.

ToxicologyToxicology

EXAM TIMEEXAM TIME


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