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1Forensic department Luyang Tao Forensic toxicologyForensic departmentLuyang Tao
2Toxicology What is toxicology? The study of the effects of poisons. Poisonous substances are produced by plants, animals, or bacteria.PhytotoxinsZootoxinsBacteriotoxinsToxicant - the specific poisonous chemical.Xenobiotic - man-made substance and/or produced by but not normally found in the body.
3IntroductionToxicology is arguably the oldest scientific discipline, as the earliest humans had to recognize which plants were safe to eat.Most exposure of humans to chemicals is via naturally occurring compounds consumed from food plants.Humans are exposed to chemicals both inadvertently and deliberately.
4History 2700 B.C. - Chinese journals: plant and fish poisons B.C. - Egyptian documents that had directions for collection, preparation, and administration of more than 800 medicinal and poisonous recipes.800 B.C. - India - Hindu medicine includesnotes on poisons and antidotes.A.D. - Greek physicians classified over600 plant, animal, and mineral poisons.
5History 50- 400 A.D. - Romans used poisons for executions and assassinations.The philosopher, Socrates, was executed using hemlock for teaching radicalideas to youths.Avicenna (A.D ) Islamic authority on poisons and antidotes.1200 A.D. - Spanish rabbi Maimonides writesfirst-aid book for poisonings,Poisons and Their Antidotes
6History Swiss physician Paracelsus (1493-1541) credited with being “the father of modern toxicology.”“All substances are poisons: there is none which is not a poison. The right dose differentiates a poison from a remedy.”
7The Dose Makes the Poison An apparently nontoxic chemical can be toxic at high doses. (Too much of a good thing can be bad).Highly toxic chemicals can be life saving when given in appropriate doses. (Poisons are not harmful at a sufficiently low dose).
8Lethal DosesApproximate Lethal Doses of Common Chemicals (Calculated for a 160 lb. human from data on rats)Chemical Lethal DoseSugar (sucrose) quartsAlcohol (ethyl alcohol) 3 quartsSalt (sodium chloride) 1 quartHerbicide (2, 4-D) one half cupArsenic (arsenic acid) teaspoonsNicotine one half teaspoonFood poison (botulism) microscopicSource: Marczewski, A.E., and Kamrin, M. Toxicology for the citizen, Retrieved August 17, 2000 from the World Wide Web:
9History Spanish physician Orfila (1815) established toxicology as a distinct scientific discipline.
10History20th CenturyPaul Ehrlich –developed staining procedures to observe cell and tissues and pioneered the understanding of how toxicants influence living organisms.
11History20th CenturyRachel Carson - alarmed public about dangers of pesticides in the environment.
13Toxicology Terms Toxicity - The adverse effects that a chemical may produce.Dose - The amount of achemical that gainsaccess to the body.
14Toxicology Terms Exposure – Contact providing opportunity of obtaining apoisonous dose.Hazard – The likelihood that thetoxicity will beexpressed.
15Threshold Effects for Dose Dose-Response RelationshipsIs there such a thing as a ‘safe’ dose??Agent AAgent BResponse“NOEL” (No Observable Effect Level)Dose
16Fundamental Rules of Toxicology Exposure must first occur for the chemical to present a risk.The magnitude of risk is proportional to both the potency of the chemical and the extent of exposure.“The dose makes the poison” (amount of chemical at the target site determines toxicity).
17Exposure Concepts Different toxic responses may arise from different: Routes of exposure.Frequencies of exposure.Duration of exposure (acute vs. chronic).
18Routes of Environmental Exposure Ingestion (water and food)Absorption (through skin)Injection (bite, puncture, or cut)Inhalation (air)
19Chemicals, Chemicals Everywhere Everything in the environment is made of chemicals. Both naturally occurring and synthetic substances are chemical in nature.People are exposed to chemicals by eating or swallowing them,breathing them, or absorbing them through the skin or mucosa.People can protect themselves by blocking these routes of exposure.
20Duration & Frequency of Exposure Duration and frequency are also important components of exposure and contribute to dose.Acute exposure - less than 24 hours; usually entails a single exposureRepeated exposures are classified as:Subacute - repeated for up to 30 daysSubchronic - repeated for daysChronic -repeated for over 90 days
21Exposure to chemicals may come from many sources: Exposure ConceptsExposure to chemicals may come from many sources:EnvironmentalOccupationalTherapeuticDietaryAccidentalDeliberate
23Individual Responses Can Be Different The variety of responses among organisms that get the same dose of chemical is due to individual susceptibility.Dose and individual susceptibility play roles in all situations involving chemicals, including those making medicine and caffeine.
24Types of Toxic Effects Death - arsenic, cyanide Organ Damage - ozone, leadMutagenesis - UV lightCarcinogenesis - benzene, asbestosTeratogenesis - thalidomide
25Target Organ Toxicity Central Nervous System – lead Immune System - isocyanatesLiver - ethanol, acetaminophenRespiratory Tract - tobacco smoke, asbestos, ozoneEye - UV light (sunlight)Kidney - metalsSkin - UV light, gold, nickelReproductive System –dibromochloropropane
26Mechanistic Toxicology How do chemicals cause their toxic effects?
27? Environmental toxicologists study the Forensic toxicologists study the application of toxicology to the law. They uses chemical analysis to determine the cause and circumstances of death in a postmortem investigation.Environmental toxicologists study theeffects of pollutants on organisms, populations, ecosystems, and the biosphere.Regulatory toxicologists use scientific data to decide how to protect humans and animals from excessive risk Government bureaus such as the FDA and EPA employ this type of toxicologist.?
28Regulatory Toxicology Use data from descriptive and mechanistic toxicology to perform risk assessments.Concerned with meeting requirements ofregulatory agencies.Industry/government interactions.
29ReviewToxicology is the science that studies the harmful effects of overexposure to drugs, environmental contaminants, and naturally occurring substances found in food, water, air, and soil.Main objectives are to establish safe doses and determine mechanisms of biologic action of chemical substances.A career in toxicology involves evaluating the harmful effects and mechanisms of action of chemicals in people, other animals, and all other living things in the environment.This work may be carried out in government, private industry and consulting firms, or universities and other research settings.Toxicologists routinely use many sophisticated tools to determine how chemicals are harmful.(e.g.) computer simulations, computer chips, molecular biology, cultured cells, and genetically-engineered laboratory animals .
30Animals in Research“Virtually every medical achievement of the last century has depended directly or indirectly on research in animals.”U.S. Public Health Service
31Summary Toxicology is a fascinating science that makes biology and chemistry interestingand relevant.Understanding HOW (i.e. mechanism)something produces a toxic effect can lead to new ways of preventing or treating chemically-related diseases. Animal use in research is essential for medical progress.Many diseases are the result of an interaction between our genetics (individual variability) and chemicals in our environment.Toxicology provides an interesting and exciting way to apply science to important problems of social, environmental, and public health significance.
34For certification as a toxicologist, an individual must possess a Ph.D. or doctorate in one of' the natural, sciences. Undergraduate degrees must also be in these areas (biology or chemistry, usually).Certification is bestowed by the American Board of Forensic Toxicology, and the expert may use the title of “Diplomate” which must be renewed every three years.
35A forensic toxicologist is normally presented with preserved samples of body fluids, stomach contents, and organ parts.They will have access to the coroner's report which should contain information on various signs and symptoms as well as other postmortem data.The toxicologist needs a through knowledge of how the body alters or metabolizes drugs because few substances leave the body in the same state as they entered.
36SCREENING TESTS Physical tests--boiling point, melting point, density, and refractive index Crystal tests--treatment with a chemical reagent to produce crystals Chemical spot tests--treatment with a chemical reagent to produce color changes Chromatography (thin-layer or gas)--used to separate components of a mixture
38Poisons"All substances are poisons; there is none which is not a poison.The right dose differentiates a poison and a remedy."Paracelsus ( )Toxicology3
39TOXICOLOGY “Science of poisons” Studies chemical effects on life forms Involves exposure of life forms to outside agents and recording subsequent effectsExposures can beoccupational or non-occupationalgas station attendant; gas station customerintentional or non-intentionalcigarette smoker, non-smoker & 2nd hand smoketoxicology studies involve intentional exposures
40PRIMARY ROUTES OF EXPOSURE IngestionInhalationAbsorptionInjection
41ROUTES OF EXPOSURE Organisms can be “dosed” in 4 ways, Inhalation - breathmost common, importantOELs based on thisIngestion - oral, gastrointestinalpoor hygiene often the causewe “dose” ourselves by ingestion oftenSkin absorption/contactthrough skin, mucous membrane contactInjection - through break in skin
42Ingestion ORAL DOSE Examples mouth to stomach Generally to the small intestine.Examplesemployee who eats lunch in the work area and ingests inorganic lead that has contaminated a sandwich.Curious child who puts a toxic substance in his or her mouth out of curiosityingestion of residue from chemicals added to our food to kill germs or parasites.
43FOOD CHAIN (ingestion)EXPOSURE Depending on the chemical,we could potentiallyeat toxic food.
44Absorption DERMAL EXPOSURE Entering the body through the skin. Substances that absorb through the skin sometimes further assimilate into the blood system.some chemicals are not absorbed easily unless the skin is cutothers are absorbed quite readily regardless of the skin’s conditionuse of proper gloves prevents skin contact/absorption through the skin
45Inhalation Breathing what is in the air which travels to the lungs. lungs are rich in blood vesselssubstances inhaled into the lungs often absorbed into the bloodstreamor may cause problems in the lung itselfWarning properties are sensory clues (odor, irritation)let us know a chemical’s presence in the atmosphere--“rotten egg” smell of H2Ssome substances have no warning propertiescarbon monoxide
46Injection Direct chemical access under the skin Ex. - medical shots, needle sticksInjection can also occur accidentally.skin cut by a contaminated can or a piece of glass.Needle sticksPowerful means of exposurecontaminant enters the bloodstream immediately.
47DOSE - RESPONSE 1 Defines a chemical’s toxic potency Related to Amount of chemical (dose) that enters or contacts the bodyThat elicits a given response, or reaction occurring after exposureFor a given exposure durationtime is an important factorHuman (or animal) variability (bell curve)
48Dose-Response (D-R) Relationship The relationship between the degree of exposure (dose) and the magnitude of the effect (response).The Occupational Environment -- Its Evaluation and Control88
49DOSE - RESPONSE 2 Dose-response designations - XYZ (generic) X = response, effectL = lethal (death)T = toxic (toxic effect)E = effective (a given effect is seen)Y = method of administrationD = dose (ingested, injected)C = concentration (inhaled)Z = magnitude of effect; % of subjects affectedmay also be a word such as “lo” (lowest dose to affect)5 or 50 = 5% or 50% of test animalsExample: LC50 = inhaled dose at which 50% of subjects died
50Dose-Response Terms 2 TDlo Toxic dose low TClo Toxic concentration low lowest dose (not inhaled) for effect except radiationTClo Toxic concentration lowlowest toxic concentration via inhalationLDlo Lethal dose lowlowest dose to kill 10% of the test population (LD10)LD50 Lethal dose 50%administered dose that kills 50% of the test populationLClo Lethal concentration low in airlowest inhaled concentration to kill a test animalLC50 Lethal concentration 50%concentration that kills 50% of the test population1110
51Dose UnitsQuantity of chemical per unit mass of body weight (i.e., mg/kg)Quantity of chemical per unit area of skin surface (mg/m2)The Occupational Environment -- Its Evaluation and Control77
52LD50The dose of chemical that causes death in 50 percent of the test animals.Approximate oral LD50 in rats often usedPROBABLE ORAL LETHAL DOSETOXICITY RATING for a 70 kg PERSON (154 lb)6 SUPER TOXIC < 5 mg/kg A TASTE (< 7 dps)5 EXTREMELY TOXIC 5-50 mg/kg BETWEEN 7 dps AND 1 tsp4 VERY TOXIC mg/kg BETWEEN 1 tsp AND 1 oz3 MODERATELY TOXIC g/kg BETWEEN 1 oz - 1 pt (1 lb)2 SLIGHTLY TOXIC 5-15 g/kg BETWEEN 1 pt - 1 qt1 PRACTICALLY NONTOXIC > 15 g/kg MORE THAN 1 qt (2.2 lb)The Occupational Environment -- Its Evaluation and Control1219
53LETHAL DOSE - LD50LD50 for a substance is established by repeated experiments with animalssubstance’s effect on humans is extrapolated to determine what the LD50 would be for humans.results are adjusted to apply to human body weight and similar characteristics.tests on animals cannot predict the exact effect that the substance will have on a human populationtoxic substance often has different effects on different speciesIn addition, scientists study the effect of a substance on human populations wherever statistics are available.Another uncertainty - most LD50 data is from acute exposure (single dose) rather than chronic testing
54TOX. STUDY LIMITATIONS Use of animal data to predict human response Use of acute exposure data to infer chronic responses in some casesUnpredictability of D-R relationshipsSo Safety factors are applied to no-effect dose to determine OELs1/10, 1/100, or 1/000 of NOELWhat if response is immediate?
56DOSE - RESPONSE 3 D-R relationship determines relative toxicity rating Rating Term LD50 LC50single oral rat 4-hr inhalation ratmg/kg ppm1 Super Toxic 5 or less < 102 Extremely Toxic3 Highly Toxic ,0004 Moderately Toxic 500-5,000 1,000-10,0005 Slightly Toxic 5,000-15,000 10, ,0006 Nearly Non-Toxic > 15,000 > 100,000
57Dose-Response Relationship The dose-response relationship(from C.D. Klaassen, Casarett and Doull’s Toxicology, 5th ed., New York: McGraw-Hill, 1996; reproduced withpermission).% MortalityGray RegionDose (mg/kg)The Occupational Environment -- Its Evaluation and Control8.125
58D-R Assumptions Chemical reacts with reactive site to produce effects Response related to concentration of agent at reactive siteConcentration at site relates to administered dose.The Occupational Environment -- Its Evaluation and Control99
59ACUTE vs CHRONIC 1 Acute Acute dose/exposure Acute response/effects short-term, limited duration usually high levelAcute response/effectsimmediate or nearly soChronicChronic dose/exposureover time, usually lower levelChronic response/effectslatent, delayed, long term
61EXPOSURE LIMITSConcentrations at or below which it is assumed most healthy workers will not have adverse health affectsSome chemicals/agents may have no safe levelNIOSH position on carcinogens (NPG Appx A)OELs per chemical may differ--WHAT IS SAFE?OELs may change with more studies, infoDifferent types of OELs consider different effectsLook up your chemical’s different OELs, recording source(s)
63CHEMICAL INTERACTIONS Combinations of chemicals can alter the usual effect of the individual chemicalsAdditive = 2toxic chemicals affecting the same organ/systemSynergistic > 2toxic chemicals enhance each other’s effectsPotentiation > 1non-toxic chemical increases the toxic effect of a toxic chemicalAntagonism < 2chemicals hinder the toxic effect(s) of one another or both (i.e., antidote)
64TOXIC EFFECTS Local vs systemic effects Acute vs chronic effects Grouped according to target organ, action &/or other factorsLocal vs systemic effectssite of contact vs. bloodstream entry, target organ/systemAcute vs chronic effectsnow vs. laterReversible vs irreversible effectsmay change w/ exposure durationAllergic and sensitization effectsantibody development; not D-R dependentVary with route & rate of entry, individual characteristics
65REPRODUCTIVE TOXINS, EFFECTS Teratogensphysical defects in embryo/fetusmother is exposed but not necessarily affectedMutagens“mutate genes”; permanent DNA changesinheritable changes (future generations)exposure to mother or fatherusually also carcinogens
66Threshold Response Non-Threshold NOEL No-observed effect-level the highest dose in an experiment which did not produce an observable effectdoesn’t mean there was no effectLOEL Lowest observed effect levelthe lowest dose which produced an observable adverse effectThe Occupational Environment -- Its Evaluation and Control1411
67Influencing Factors Concentration Duration and frequency of exposure Route of entryInterspecies variationIntraspecies variationEnvironmental factorsChemical combinationsThe Occupational Environment -- Its Evaluation and Control1512
68Intraspecies Variation Age and maturityGender and hormonal statusGenetic makeupState of healthOvert and covert factors that make us all different, individual, also can affect the way our body responds to exposure13
69Concentration Units Mass Per Volume Ratio, % volume (ppm = % x 10,000) mg/m3 milligrams per cubic meter/m3 micrograms per cubic meterg/m3 nanograms per cubic meterRatio, % volume (ppm = % x 10,000)PPM- Parts of a substance per million parts of air(e.g.: 1 inch in 16 miles), 1 minute in 2 yearsPPB- Parts of a substance per billion parts of air(e.g.: 1 inch in miles), 1 second in 32 yearsPPT- Parts of a substance per trillion parts of air(e.g.: 1 inch in 16 million miles, 1 second in 320 centuries1916
70Exposures that Reduce Life Expectancy by 8 Min. Smoking 1.4 cigarettesLiving 2 months with a cigarette smokerEating 100 charcoal-broiled steaks1 X-Ray (in a good hospital)Eating 40 tablespoons of peanut butterDrinking 10, ounce soft drinks from banned plastic bottlesDrinking ounce cans of diet soda containing saccharinLiving 20 years near a polyvinyl chloride plantLiving 15 years within 30 miles of a nuclear-power plantWilson, R.: "A Rational Approach to Reducing Cancer Risk." New York Times, July 7, 1978.21The Occupational Environment -- Its Evaluation and Control18
71TOX. SUMMARY Toxicology continues to evolve, increase in importance Researching chemical effectsOccupationalEnvironmentalMedicalOften “educated guesswork”Essential to continuing health of humanity
72TOXINS IN OUR BODY THE BRAIN CIRCULATORY SYSEM RESPIRATORY SYSTEMS HEARTSTOMACHLIVER & KIDNEYINTESTINE
75Forensic Science What is it? Components- Applied Science Legal/Courts & TestimonyFacilities
76Science and the LawScientific MethodForensic ProcessR.I.I.R.
77Scope of Forensic Science CriminalisticsSpecialitiesMedicineAnthropologyOdontologyEntomologyOthers
78History of Forensic Science Chinese medicine-6th Century1839-MJB Orfila, toxicologyLate 1800s-Alexandre Lacassagne, ballistics and bloodstain patterns1910-Edmund Locard, exchange principle1924-August Vollmer, LAPD crime lab1932-FBI Laboratory, fingerprints
79Forensic Science in USA and china FederalStateLocalPrivate
80Information from Physical Evidence Corpus delictiModus operandiLinkage – Locard Exchange PrincipleDisproving/Supporting Witnesses’ StatementsIdentification of suspects/victimsProvide for investigative leads
81Forensic Testing Methods Comparison TestingUnknown Known or StandardEvidence “Origin or Source”Class Characteristics vs.IndividualizingCharacteristics
82Types of Physical Evidence Various definitions“Animal, vegetable or mineral”Chemical, biological, or microscopic
83Specific Areas of Forensic Science Impression EvidenceFingerprintsFootwear/TiresTrace EvidenceHairsFibersPaintGlassChemical EvidenceDrugsAccelerantsBiological EvidenceOther AreasToxicologyAnthropologyOdontology