forensic toxicology forensic department luyang tao

Forensic toxicology

Forensic department

Luyang Tao

ToxicologyWhat is toxicology? The study of the effects of poisons.

Poisonous substances are produced by plants, animals, or bacteria.

Phytotoxins Zootoxins Bacteriotoxins

Toxicant - the specific poisonous chemical.

Xenobiotic - man-made substance and/or produced by but not normally found in the body.

IntroductionToxicology 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.

2700 B.C. - Chinese journals: plant and fish poisons

1900-1200 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 includes notes on poisons and antidotes.

50-100 A.D. - Greek physicians classified over 600 plant, animal, and mineral poisons.

History

History50- 400 A.D. - Romans used poisons for

executions and assassinations.

The philosopher, Socrates, was executed using hemlock for teaching radical

ideas to youths.

Avicenna (A.D. 980-1036) Islamic authority on poisons and antidotes.

1200 A.D. - Spanish rabbi Maimonides writes

first-aid book for poisonings,

Poisons and Their Antidotes

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.”

History

The 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).

Lethal Doses

Source: Marczewski, A.E., and Kamrin, M. Toxicology for the citizen, Retrieved August 17, 2000 from the World Wide Web: www.iet.msu.edu/toxconcepts/toxconcepts.htm.

Approximate Lethal Doses of Common Chemicals(Calculated for a 160 lb. human from data on rats)

Chemical Lethal Dose

Sugar (sucrose) 3 quarts

Alcohol (ethyl alcohol) 3 quarts

Salt (sodium chloride) 1 quart

Herbicide (2, 4-D) one half cup

Arsenic (arsenic acid) 1-2 teaspoons

Nicotine one half teaspoon

Food poison (botulism) microscopic

Spanish physician Orfila (1815) established toxicology as

a distinct scientific discipline.

History

20th Century

Paul Ehrlich –developed staining procedures to observe cell and tissues and pioneered the understanding of how toxicants influence living organisms.

History

20th Century

Rachel Carson - alarmed public about dangers of pesticides in the environment.

History

Modern Toxicology

Toxicity - The adverse effects that a chemical

may produce.

Dose - The amount of a chemical that gains access to the body.

Toxicology Terms

Exposure – Contact providing opportunity of obtaining a poisonous dose.

Hazard – The likelihood that the toxicity will be expressed.

Toxicology Terms

Threshold Effects for Dose

Is there such a thing as a ‘safe’ dose??

Agent A

Agent B

Dose

Res

pons

e

“NOEL”(No Observable Effect Level)

Dose-ResponseRelationships

Fundamental 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).

Exposure Concepts

Different toxic responses may arise from different:

– Routes of exposure.

– Frequencies of exposure.

– Duration of exposure (acute vs. chronic).

Routes of Environmental Exposure

Ingestion (water and food)

Absorption (through skin)

Injection (bite, puncture, or cut)

Inhalation (air)

Chemicals, 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.

Duration & 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 exposure

Repeated exposures are classified as:– Subacute - repeated for up to 30 days– Subchronic - repeated for 30-90 days– Chronic -repeated for over 90 days

Exposure ConceptsExposure to chemicals may come from many sources:

– Environmental– Occupational– Therapeutic– Dietary– Accidental– Deliberate

Children & Poisons

Individual 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.

Types of Toxic Effects

Death - arsenic, cyanide

Organ Damage - ozone, lead

Mutagenesis - UV light

Carcinogenesis - benzene, asbestos

Teratogenesis - thalidomide

Target Organ Toxicity

Central Nervous System – leadImmune System - isocyanatesLiver - ethanol, acetaminophenRespiratory Tract - tobacco smoke,

asbestos, ozoneEye - UV light (sunlight)Kidney - metals Skin - UV light, gold, nickelReproductive System – dibromochloropropane

Mechanistic Toxicology

How do chemicals cause their toxic effects?

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 the effects 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.

?

Regulatory Toxicology

Use data from descriptive and mechanistic toxicology to perform risk assessments.

Concerned with meeting requirements of

regulatory agencies.

Industry/government interactions.

ReviewToxicology 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 .

Animals in Research

“Virtually every medical achievement of the last century has depended directly or indirectly on research in animals.”

U.S. Public Health Service

SummaryToxicology is a fascinating science that

makes biology and chemistry interesting and 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.

The power of EDUCATION

• For 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.

• A forensic toxicologist is normally presented A forensic toxicologist is normally presented with preserved samples of body fluids, stomach with preserved samples of body fluids, stomach contents, and organ parts. contents, and organ parts.

• They will have access to the coroner's report They will have access to the coroner's report which should contain information on various which should contain information on various signs and symptoms as well as other signs and symptoms as well as other postmortem data. postmortem data.

• The toxicologist needs a through knowledge of The toxicologist needs a through knowledge of how the body alters or metabolizes drugs how the body alters or metabolizes drugs because few substances leave the body in the because few substances leave the body in the same state as they entered.same state as they entered.

SCREENING TESTS

Physical tests--boiling point, melting point, Physical tests--boiling point, melting point, density, and refractive indexdensity, and refractive index

Crystal tests--treatment with a chemical Crystal tests--treatment with a chemical reagent to produce crystalsreagent to produce crystals

Chemical spot tests--treatment with a Chemical spot tests--treatment with a chemical reagent to produce color changeschemical reagent to produce color changes

Chromatography (thin-layer or gas)--used to Chromatography (thin-layer or gas)--used to separate components of a mixtureseparate components of a mixture

Forensic ToxicologyForensic Toxicology

Forensic department Forensic department

Shizhong bian Shizhong bian

Poisons

"All substances are poisons; there is none which is not a poison.

The right dose differentiates a poison and a remedy."

Paracelsus (1493-1541)

Toxicology

TOXICOLOGY

• “Science of poisons”• Studies chemical effects on life forms

– Involves exposure of life forms to outside agents and recording subsequent effects

• Exposures can be– occupational or non-occupational

• gas station attendant; gas station customer

– intentional or non-intentional• cigarette smoker, non-smoker & 2nd hand smoke• toxicology studies involve intentional exposures

PRIMARY ROUTES OF EXPOSURE

IngestionIngestion InhalationInhalation

AbsorptionAbsorption InjectionInjection

ROUTES OF EXPOSUREOrganisms can be “dosed” in 4 ways, Inhalation - breath• most common, important• OELs based on this

Ingestion - oral, gastrointestinal• poor hygiene often the cause• we “dose” ourselves by ingestion often

Skin absorption/contact• through skin, mucous membrane contact Injection - through break in skin

Ingestion• ORAL DOSE

– mouth to stomach Generally to the small intestine.

• Examples• employee 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 curiosity

• ingestion of residue from chemicals added to our food to kill germs or parasites.

FOOD CHAIN (ingestion)EXPOSURE

Depending on the chemical, we could potentiallyeat toxic food.

AbsorptionDERMAL 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 cut

• others are absorbed quite readily regardless of the skin’s condition

• use of proper gloves prevents skin contact/absorption through the skin

InhalationBreathing• what is in the air which travels to the lungs. • lungs are rich in blood vessels• substances inhaled into the lungs often absorbed into the

bloodstream– or may cause problems in the lung itself

• Warning properties are sensory clues (odor, irritation) – let us know a chemical’s presence in the atmosphere--“rotten

egg” smell of H2S

– some substances have no warning properties• carbon monoxide

InjectionDirect chemical access under the skin• Ex. - medical shots, needle sticks• Injection can also occur accidentally.

– skin cut by a contaminated can or a piece of glass. – Needle sticks

• Powerful means of exposure – contaminant enters the bloodstream immediately.

DOSE - RESPONSE 1

Defines a chemical’s toxic potency

Related to

• Amount of chemical (dose) that enters or contacts the body

• That elicits a given response, or reaction occurring after exposure

• For a given exposure duration– time is an important factor

• Human (or animal) variability (bell curve)

8The Occupational Environment -- Its Evaluation and Control

Dose-Response (D-R) Relationship

• The relationship between the degree of exposure (dose) and the magnitude of the effect (response).

DOSE - RESPONSE 2Dose-response designations - XYZ (generic)• X = response, effect

– L = lethal (death)– T = toxic (toxic effect)– E = effective (a given effect is seen)

• Y = method of administration– D = dose (ingested, injected) – C = concentration (inhaled)

• Z = magnitude of effect; % of subjects affected– may also be a word such as “lo” (lowest dose to affect)– 5 or 50 = 5% or 50% of test animals

Example: LC50 = inhaled dose at which 50% of subjects died

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Dose-Response Terms 2

TDlo Toxic dose lowlowest dose (not inhaled) for effect except radiation

TClo Toxic concentration low lowest toxic concentration via inhalation

LDlo Lethal dose low lowest dose to kill 10% of the test population (LD10)

LD50 Lethal dose 50% administered dose that kills 50% of the test population

LClo Lethal concentration low in airlowest inhaled concentration to kill a test animal

LC50 Lethal concentration 50% concentration that kills 50% of the test population


Dose Units

• Quantity of chemical per unit mass of body weight (i.e., mg/kg)

• Quantity of chemical per unit area of skin surface (mg/m2)


LD50

• The dose of chemical that causes death in 50 percent of the test animals.– Approximate oral LD50 in rats often used

PROBABLE ORAL LETHAL DOSE

TOXICITY 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 tsp

4 VERY TOXIC 50-500 mg/kg BETWEEN 1 tsp AND 1 oz

3 MODERATELY TOXIC0.5-5 g/kg BETWEEN 1 oz - 1 pt (1 lb)

2 SLIGHTLY TOXIC 5-15 g/kg BETWEEN 1 pt - 1 qt

1 PRACTICALLY NONTOXIC > 15 g/kg MORE THAN 1 qt (2.2 lb)

LETHAL DOSE - LD50

• LD50 for a substance is established by repeated experiments with animals

• substance’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 population

– toxic substance often has different effects on different species

• In 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

TOX. STUDY LIMITATIONS

• Use of animal data to predict human response

• Use of acute exposure data to infer chronic responses in some cases

• Unpredictability of D-R relationships

So Safety factors are applied to no-effect dose to determine OELs– 1/10, 1/100, or 1/000 of NOEL

– What if response is immediate?


AGENT LD50

(mg/kg)• ETHYL ALCOHOL 7060• SODIUM CHLORIDE 3000• NAPHTHALENE 1760• FERROUS SULFATE 1500• ASPIRIN 1000• FORMALDEHYDE 800• AMMONIA 350• DEXTROMETHORPHAN HYDROBROMIDE 350• CAFFEINE 192• PHENOBARBITAL 150• CHLORPHENIRAMINE MALEATE 118• DDT 100• STRYCHNINE SULFATE 2• NICOTINE 1• DIOXIN 0.0001• BOTULINUS TOXIN 0.00001

DOSE - RESPONSE 3

D-R relationship determines relative toxicity rating

Rating Term LD50 LC50single oral rat 4-hr inhalation ratmg/kg ppm

1 Super Toxic 5 or less < 10

2 Extremely Toxic 5-50 10-100

3 Highly Toxic 50-500 100-1,000

4 Moderately Toxic 500-5,000 1,000-10,000

5 Slightly Toxic 5,000-15,000 10,000-100,000

6 Nearly Non-Toxic > 15,000 > 100,000

8.1The Occupational Environment -- Its Evaluation and Control

Dose-Response Relationship

Dose (mg/kg)

% M

ort

ality

Gray Region

The dose-response relationship

(from C.D. Klaassen, Casarett and Doull’s Toxicology, 5th ed., New York: McGraw-Hill, 1996; reproduced with permission).


D-R Assumptions

• Chemical reacts with reactive site to produce effects

• Response related to concentration of agent at reactive site

• Concentration at site relates to administered dose.

ACUTE vs CHRONIC 1Acute

• Acute dose/exposure– short-term, limited duration usually high level

• Acute response/effects– immediate or nearly so

Chronic

• Chronic dose/exposure– over time, usually lower level

• Chronic response/effects– latent, delayed, long term

ACUTE vs CHRONIC 2

ACUTE DOSE CHRONIC DOSE

ACUTERESPONSE

Manure pit entry – O2deficiencyCausing death

FormaldehydeexposureCausingsensitization(allergic reaction)

CHRONICRESPONSE

Radiation exposureCausing cancer

Cigarette smokingCausing cancer,emphysema

EXPOSURE LIMITS

• Concentrations at or below which it is assumed most healthy workers will not have adverse health affects

• Some chemicals/agents may have no safe level– NIOSH position on carcinogens (NPG Appx A)

• OELs per chemical may differ--WHAT IS SAFE?

• OELs may change with more studies, info

• Different types of OELs consider different effects

• Look up your chemical’s different OELs, recording source(s)

Exposure Limits SummaryExposure Limit Acronym Agency Definition

Time WeightedAverage

TWA All Denotes an average of the total exposure over a designated period of time. Unless otherwise designated, the time is usually 8 hr.

PermissibleExposure Limit

PEL OSHA Concentration to which most workers can be exposed 8 hr/day, 40 hr/weekwithout adverse health effects. (NPG, 29CFR1910.1000 - Z tables)

Threshold LimitValue

TLV ACGIH Same as PEL for 8-hr TWA (TLV)

RecommendedExposure Limit

REL NIOSH Concentration to which most workers can be exposed 10 hr/day, 40 hr/weekwithout adverse health effects. (NPG)

Short TermExposure Limit

STEL All Concentration at which exposures should be limited to 15 min. duration normore than 4 times/day, with at least 1 hour between exposures, assuming theTWA is not exceeded. (NPG, TLV)

Ceiling C All Concentration that should never be exceeded, even instantaneously(NPG, TLV)

ImmediatelyDangerous toLife and Health

IDLH NIOSH,MSHA

Concentration likely to cause death or permanent adverse health effects orprevent escape from the environment (narcosis, irritation); worker couldescape from environment in the event of respirator failure (NPG)

Skin S All Substance can be absorbed through the skin and this route of exposure must beconsidered when assessing overall exposure potential. (NPG, TLV)

CHEMICAL INTERACTIONSCombinations of chemicals can alter the usual effect of the individual

chemicals• Additive 1 + 1 = 2

– toxic chemicals affecting the same organ/system • Synergistic 1 + 1 > 2

– toxic chemicals enhance each other’s effects• Potentiation 1 + 0 > 1

– non-toxic chemical increases the toxic effect of a toxic chemical• Antagonism 1 + 1 < 2

– chemicals hinder the toxic effect(s) of one another or both (i.e., antidote)

TOXIC EFFECTSGrouped according to target organ, action &/or other factors

• Local vs systemic effects– site of contact vs. bloodstream entry, target organ/system

• Acute vs chronic effects– now vs. later

• Reversible vs irreversible effects– may change w/ exposure duration

• Allergic and sensitization effects– antibody development; not D-R dependent

Vary with route & rate of entry, individual characteristics

REPRODUCTIVE TOXINS, EFFECTS

Teratogens

• physical defects in embryo/fetus

• mother is exposed but not necessarily affected

Mutagens

• “mutate genes”; permanent DNA changes

• inheritable changes (future generations)

• exposure to mother or father

• usually also carcinogens


Threshold Response

Non-Threshold

• NOEL No-observed effect-level – the highest dose in an experiment which did not produce an observable

effect• doesn’t mean there was no effect

• LOEL Lowest observed effect level– the lowest dose which produced an observable adverse effect


Influencing Factors

• Concentration

• Duration and frequency of exposure

• Route of entry

• Interspecies variation

• Intraspecies variation

• Environmental factors

• Chemical combinations

Intraspecies Variation

• Age and maturity

• Gender and hormonal status

• Genetic makeup

• State of health

Overt and covert factors that make us all different, individual, also can affect the way our body responds to exposure

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Concentration UnitsMass Per Volume• mg/m3 milligrams per cubic meter

• /m3 micrograms per cubic meter

• g/m3 nanograms per cubic meter

Ratio, % 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 years

• PPB- Parts of a substance per billion parts of air– (e.g.: 1 inch in 16 000 miles), 1 second in 32 years

• PPT- Parts of a substance per trillion parts of air– (e.g.: 1 inch in 16 million miles, 1 second in 320 centuries


Exposures that Reduce Life Expectancy by 8 Min.

• Smoking 1.4 cigarettes

• Living 2 months with a cigarette smoker

• Eating 100 charcoal-broiled steaks

• 1 X-Ray (in a good hospital)

• Eating 40 tablespoons of peanut butter

• Drinking 10,000 24-ounce soft drinks from banned plastic bottles

• Drinking 30 12-ounce cans of diet soda containing saccharin

• Living 20 years near a polyvinyl chloride plant

• Living 15 years within 30 miles of a nuclear-power plant

Wilson, R.: "A Rational Approach to Reducing Cancer Risk." New York Times, July 7, 1978.

TOX. SUMMARY

Toxicology continues to evolve, increase in importance

• Researching chemical effects

• Occupational

• Environmental

• Medical

• Often “educated guesswork”

• Essential to continuing health of humanity

CIRCULATORYSYSEM

RESPIRATORYSYSTEMS

HEART

STOMACH

LIVER & KIDNEY

INTESTINE

THE BRAIN

TOXINS IN OUR BODY

Forensic Sciencefor Educators

Presentation Objectives

• Forensic Science 101

• Teaching forensic science

Forensic Science

• What is it?

• Components-– Applied Science

– Legal/Courts & Testimony

– Facilities

Science and the Law

• Scientific Method

• Forensic Process

R.I.I.R.

Scope of Forensic Science

• Criminalistics

• Specialities– Medicine

– Anthropology

– Odontology

– Entomology

– Others

History of Forensic Science

• Chinese medicine-6th Century

• 1839-MJB Orfila, toxicology

• Late 1800s-Alexandre Lacassagne, ballistics and bloodstain patterns

• 1910-Edmund Locard, exchange principle

• 1924-August Vollmer, LAPD crime lab

• 1932-FBI Laboratory, fingerprints

Forensic Science in USA and china

• Federal

• State

• Local

• Private

Information from Physical Evidence

• Corpus delicti

• Modus operandi• Linkage – Locard Exchange Principle

• Disproving/Supporting Witnesses’ Statements

• Identification of suspects/victims

• Provide for investigative leads

Forensic Testing Methods• Comparison Testing

Unknown Known or Standard

Evidence “Origin or Source”

• Class Characteristics vs.

Individualizing

Characteristics

Types of Physical Evidence

• Various definitions

• “Animal, vegetable or mineral”

• Chemical, biological, or microscopic

Specific Areas of Forensic Science

• Impression Evidence– Fingerprints

– Footwear/Tires

• Trace Evidence– Hairs

– Fibers

– Paint

– Glass

• Chemical Evidence– Drugs

– Accelerants

• Biological Evidence

• Other Areas– Toxicology

– Anthropology

– Odontology

Real CSI….

• CS Investigators

• Physical Evidence

• Forensic Science

Teaching Forensic Science

• Available resources

• Specific useful resources

• Practical exercises-• Generally

• Today

Resources

• Undergraduate programs

• American Academy of Forensic Science

• Websites of Interest

• Forensic Companies

• Textbooks

• Other Educational Materials

©2004 Marilyn T. Miller

Educational Materials


Forensic Science in the Classroom

• Some states have adopted a

standards-based curriculum

• Elective course

• 11th or 12th Grade

• Job shadowing

• Post-secondary articulation


TN Course Standards

• Std 1-History• Std 2-Careers• Std 3-Legal Aspects• Std 4-Safety• Std 5-Collection, Packaging

Evidence• Std 6-Lab Capabilities• Std 7-Drug Analysis

• Std 8-DNA• Std 9-Lab Instrumentation• Std 10-Technology in the

Forensic Lab• Std 11-PE at scene• Std 12-Human features for

identification


In the Classroom

• A wide variety of sections possible with applied science topics

• Fingerprints

• Bloodstain Patterns


Conclusion

• Fun and exciting exposure to science

• Not a replacement for physical science

Thanks Thanks

forensic toxicology forensic department luyang tao

Documents

history slide

modern toxicology slide

toxicology terms

poisonous dose

effects of poisons

established toxicology

introduction toxicology

fish poisons