Forensic Toxicology dr Paweł Szpot - PowerPoint Presentation

Slide1

Forensic Toxicology

dr Paweł Szpot

Chair and

Department

of

Forensic

Medicine

Wroclaw

Medical

University

Slide2

Introduction:

Forensic toxicology encompasses the analysis

of

drugs and chemicals including the

most common drugs of abuse and also focuses on the interpretation, that is, the understanding

and appreciation of the results of this testing in a medical–legal context.

The results of toxicology testing are often presented to courts

for the adjudication of an issue but are very often misunderstood.

We need to remember that a test is not a test. A test result is only as good as the

question it is asked to answer. Toxicology test results must, therefore, be introduced

by qualified toxicologists.

The traditional specimens used in testing include blood or its component parts, that is, plasma or serum, and urine. This is in part because these are the easiest to collect. In addition, in the case of blood, or its components, it represents the dynamic state of drug distribution in the body with the best relation to the state of the individual’s pharmacologic condition (therapeutic, impairment, and death). In the case of urine, we have a static fluid that generally does not correlate with the pharmacological effects in an individual, rather it represents high concentrations of drugs and metabolites and demonstrates prior use. Thus, the ready accessibility and knowledge of the pharmacokinetics and distribution of drugs caused toxicologists to focus on these specimens

.

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Topics:

Biological

evidence

possible

to

preserve

and

use

in

toxicological

analyses

.

Toxic

substances

classification

for the

forensic

purposes

.

Toxic

metals

and

their

characteristics

.

Toxic

gases

and

easily

evaporating

substances

,

toxic

organic

solvents

.

Toxic

non-

narcotic

substances

derived

from

plants

.

Narcotics

substances

intoxications

–

characteristics

,

ways

od

administering

,

mechanisms

of

action

,

possibilities

of

detection

in

organic

materials.

Carbon

monoxide

intoxication

–

sources

,

characteristics

,

mechanism

of

action

,

possibilities

of

detection

in

organic

materials.

Forensic

interpretation

of

state

after

consuming

ethanol

,

drunk

state

and

state

after

consuming

narcotic

substances

.

Possibilities

of

calculating

ethanol

level

at

a

given

time

in the past

using

results

of

toxicological

tests

performed

.

Slide4

Biological

evidence

possible

to

preserve

and use in toxicological analyses.

Material should include: Place of xenobiotic penetration into the body Blood which distributes xenobiotic to the organs Place of xenobiotic eliminationPlace of a possible xenobiotic accumulation To the untargeted study we take: stomachgastric buffers the small intestinethe content of the small intestinebloodliverbilekidneyurine

It’s

recommended by the Polish Society of Forensic Medicine and Criminology

to

take

50 g

of

tissue

and 30 ml of tissue fluids

Slide5

Packing for storing the

taken

material for

toxicological studies

has

to be: Chemically pure and inert H

ermetically sealed The material should be properly described. The description should include information such as: Name of deceasedAge (if known) or date of birthType of materialDate of SectionName of person performing the autopsyThe registration number of books autopsy

Slide6

From:

A Simplified Guide to Forensic

Toxicology

Slide7

Material

type and quantity

-

special

cases

-

Slide8

Signs

of

injection

Cut about 1-2 cm2 of skin, subcutaneous tissue and the superficial layer of muscle from place which shows signs of injection. This section is inserted into the plastic tube. In comparison, to the other tube you have to cut out the same size piece of skin, but from place which does not contain a trace of

injection.

The fragment with a trace of injection will have higher concentration of xenobiotic that has entered the body by injection

Slide9

Suspected

carbon

monoxide

poisoning

In the case of carbon monoxide poisoning collect blood from the right and left ventricle to compare the concentration of carboxyhemoglobin in the blood. If someone died in an atmosphere containing carbon monoxide

, there will be higher concentration of carboxyhemoglobin in the left ventricle (coming from lungs).

Slide10

Hair and

nails

Hair and nails are a new trend in

forensic

toxicology. They may be taken for toxicological studies

from bodies in which any of soft tissues have survived (e. g. in the exhumation of the old corpses).

Slide11

Toxic substances

classification

for the

forensic

purposes.

The degree of toxicity Lethal dose for an adult humanextremely toxic a few dropshighly toxicteaspoonmedium toxic30 or 30 cm3a little toxic250-500 g

practically

nontoxic

1 dm3

or

1 kg

practically

harmless

o

ver 1 kg or 1 dm3

Classification

by Prof. S.

Raszeja

„Medycyna sądowa”

Slide12

Another classification

due to changes in the body

:

The poisons that cause distinct

changes:

1. locally acting - acids, alkalis, bromine, iodine - if they come into contact with body tissue

they cause

necrosis and denaturation of proteins2. parenchymal - metals, salts of heavy metals, fungi –damaging the kidneys, liver, heartThe poisons that may not result in significant changes (but not necessarily):1. The volatile - act mainly on the central nervous system - the solvents, alcohols, hydrocarbons2. The blood - carbon monoxide, cyanides, phenols, benzene, medicines, drugs, pesticides3. Acting on a functional way - without causing any apparent damage visible at autopsy – drugs and pesticides.

Slide13

Basic effects of possible multiple interactions concerning the main toxic and/or essential metals and m

e

talloids

in mammals

Toxic

metal

or

metalloidBasic effects of the interaction with other metal or metalloidArsenic (As)Affects the distribution of Cu (an increase of Cu in the kidney, and a decrease of Cu in the liver, serum and urine).Impairs the metabolism of Fe (an increase of Fe in the liver with concomitant decrease in haematocrit).Zn decreases the absorption rate of inorganic As and decreases the toxicity of As.Se decreases the toxicity of As and vice versa.Arsenic toxicity is a global health problem affecting millions of people. Contamination is caused by arsenic from natural geological sources leaking into aquifers, contaminating drinking water and may also occur from mining and other industrial processes. Arsenic is present as a contaminant in many traditional remedies. Arsenic trioxide is now used to treat acute promyelocytic leukaemia. Absorption occurs predominantly from ingestion from the small intestine, though minimal absorption occurs from skin contact and inhalation. Arsenic exerts its toxicity by inactivating up to 200 enzymes, especially those involved in cellular energy pathways and DNA synthesis and repair. Acute arsenic poisoning is associated initially with nausea, vomiting, abdominal pain, and severe diarrhoea. Encephalopathy and peripheral neuropathy are reported. Chronic arsenic toxicity results in multisystem disease. Arsenic is a well documented human carcinogen affecting numerous organs.

Slide14

Basic effects of possible multiple interactions concerning the main toxic and/or essential metals and m

e

talloids

in mammals

Toxic

metal

or

metalloidBasic effects of the interaction with other metal or metalloidMercury (Hg)Affects the distribution of Cu (an increase of Cu in the liver).Zn decreases the absorption rate of inorganic Hg and decreases the toxicity of Hg.Se decreases the toxicity of Hg.Cd increases the concentration of Hg in the kidney, but at the same time decreases the toxicity of Hg in the kidney (the influence of the Cd-induced metallothionein synthesis).

Slide15

Basic effects of possible multiple interactions concerning the main toxic and/or essential metals and m

e

talloids

in mammals

Toxic

metal

or

metalloidBasic effects of the interaction with other metal or metalloidLead (Pb)Impairs the metabolism of Ca; deficient dietary Ca increases the absorption rate of inorganic Pb and increases the toxicity of Pb.Impairs the metabolism of Fe; deficient dietary Fe increases the toxicity of Pb, whereas its influence on the absorption rate of Pb is equivocal.Impairs the metabolism of Zn and increases urinary excretion of Zn; deficient dietary Zn, increases the absorption rate of inorganic Pb and increases the toxicity of Pb.Se decreases the toxicity of Pb.Data on interactions with Cu and Mg are equivocal (i.e., the possible role of Zn, or another metal, as a mediator).

Slide16

Toxic

gases

and

easily

evaporating substances, toxic organic solvents.

Toxic methanol, ethylene glycol, isopropyl alcohol Methyl alcohol - colorless liquid with a slightly sweet, strong aroma, properties very similar to ethyl alcohol therefore, in industries where it is used, there are cases of mistaken consumption of alcohol instead of ethyl. Absorbed through the skin, lungs (vapors), the poisoning occurs mostly via the oral route. In the body breaks down into formaldehyde and then to formic acid, which are very toxic and lead to metabolic acidosisLethal dose is 30 to 150 ml

Slide17

Methanol

loss of consciousness, impaired

breathing,

impaired

liver function and damage to

the optic nerve and retina causing blurred vision, blindness

, may cause swelling of the brain, kidney failure

Slide18

Isopropyl alcohol

Isopropyl alcohol (

2-propanol)

colorless

, volatile liquid with a

bitter characteristic smell. Application:component of

window cleaning fluidscomponent of antifreeze fluid for coolinghospitals (liquids to decontaminate the surface)For a healthy human adult (weighingapproximately 80 kg) lethal dose byingestion of 2-propanol is about 240 ml

Slide19

Isopropanol

Isopropanol

vapor

act

locally, irritating the eyes,

mucous membranes of the nose and throatAfter ingestion causes nausea, abdominal pain, vomiting Just as ethanol affects the central nervous system,causing agitation, blurred visionHigh concentrations of isopropanol:convulsions, coma, respiratory distress

respiratory

paralysis

Abnormal

heart

rate

,

blood

pressure

,

blood

clotting disorders, liver

damage

and

kidney

Slide20

Ethylene

glicol

colorless, odorless, oily and sweet liquid,

soluble in water and ethanolToxic dose of 30-50 ml,

Lethal dose of 100-150 mlApplication:solvent for inkscomponent of antifreeze fluid for cooling automotive engines, a component of brake fluidpoisoning occurs by mistaken or suicidal drinking liquid containing ethylene glycol

Slide21

Ethylene glicol

morphological changes:

The organs and tissues states the following:

swelling,

bleedings,

Degenerative changes of the heart muscle, liver and kidney,

The precipitated calcium oxalate

crystals in renal tubular light -histological marker

Slide22

Carbon monoxide

poisoning

Determination

of

carboxyhemoglobin

(

CoHb

) in the bloodAbout 75% of all poisonings are caused by a suicide from carbon monoxideCarbon monoxide is a toxic gas, colorless, odorless, it is very difficult for detectionCarbon monoxide is a product of incomplete combustion of organic matter due to insufficient oxygen supply to enable complete oxidation to carbon dioxide (CO2)

Slide23

Toxicity

mechanism

of

carbon

monoxideCarbon monoxide connects

with hemoglobin to carboxyhemoglobin (HbCO) in the human blood. This prevents oxygen binding to hemoglobin, reducing the oxygen-carrying capacity of the blood and leading to hypoxia

Slide24

Carbon monoxide is absorbed into the body

from the respiratory tract (very rapidly

absorbed by the alveoli), the skin

Carbon monoxide binds to hemoglobin (

Hb

),

ferritin, and myoglobin 200 - 300 times faster

than oxygenProlonged exposure can lead to brain damage and even death.

medical opinion is based on the results of

an autopsy or examination and the determination of carboxyhemoglobin in the blood of the deceased

o

n the basis of determination of blood carboxyhemoglobin obtain information about the cause of the poisoning or death

Slide25

Clinical Signs & Symptoms associated with CO

Poisoning and correlated

COHb

levels

The severity of hypoxia and shock carbon monoxide

CoHb concentrationSigns & SymptomsMild<15 - 20%Headache, Nausea, Vomiting, Dizziness, Blurred Vision

Moderate

21 - 40%*

Confusion, Syncope, Chest Pain,

Dyspnea

, Weakness, Tachycardia,

Tachypnea

Severe

41 - 59%*

Palpitations,

Dysrhythmias

, Hypotension, Myocardial ischemia, Cardiac

arrest, Respiratory arrest, Pulmonary edema, Seizures

Fatal

60+%

sometimes

>50%

Death

,

Slide26

Toxic non-narcotic substances derived from plants

The

European

Yew

(

Taxus baccata, family: Taxaceae) is a

coniferous, evergreen poisonous shrub or tree commonly used for ornamental landscaping (e.g., parks, gardens, and churchyards) or for pharmaceutical purposes. The toxic nature of the yew plant has been known for more than 2000 years. The lethal dose for an adult is reported to be 50 g of yew needles equal to 250 mg taxine alkaloids or approximately 3 mg taxine per kilogram body weight.

Taxus

baccata

contains

a

complex

mixture

characterized

by the

taxane

ring system skeleton, including non-alkaloidal diterpenoids (e.g., 10-deactetylbaccatin III), alkaloidal diterpenoids [e.g., paclitaxel (taxol

A),

taxine

B],

or

phenolic

constituents

(

e.g

., 3,5-dimethoxyphenol),

flavonoids

(

e.g

.,

myricetin

), and

biflavonoids

(

e.g

.,

bilobetin

),

among

others

.

Slide27

Toxic non-

narcotic

substances

derived

from plantsAmanita phalloides

, commonly known as the death cap, is a deadly poisonous basidiomycete fungus, one of many in the genus Amanita. Widely distributed across Europe, A. phalloides forms ectomycorrhizas with various broadleaved trees. In some cases, the death cap has been introduced to new regions with the cultivation of non-native species of oak, chestnut, and pine. The large fruiting bodies (mushrooms) appear in summer and autumn; the caps are generally greenish in color, with a white stipe and gills.These toxic mushrooms resemble several edible species (most notably caesar's mushroom and the straw mushroom) commonly consumed by humans, increasing the risk of accidental poisoning. A. phalloides is one of the most poisonous of all known toadstools. It has been involved in the majority of human deaths from mushroom poisoning, possibly including the deaths of Roman Emperor Claudius in AD 54 and Holy Roman Emperor Charles VI in 1740. It has been the subject of much research, and many of its biologically active agents have been isolated. The principal toxic constituent is α-amanitin, which damages the liver and kidneys, often fatally.As the common name suggests, the fungus is highly toxic, and is responsible for the majority of fatal mushroom poisonings worldwide. Its biochemistry has been researched intensively for decades, and 30 grams (1 oz), or half a cap, of this mushroom is estimated to be enough to kill a human. In 2006, a family of three in Poland was poisoned, resulting in one death and the two survivors requiring liver transplants. Some authorities strongly advise against putting suspected death caps in the same basket with fungi collected for the table and to avoid touching them. Furthermore, the toxicity is not reduced by cooking, freezing, or drying.

Slide28

Digitalis

A group of medicines extracted from foxglove plants are called

digitalin

. The use of D.

purpurea

extract containing cardiac glycosides for the treatment of heart conditions was first described in the English-speaking medical literature by William Withering, in

1785, which is considered the beginning of modern therapeutics

.Digitalis toxicity (Digitalis intoxication) results from an overdose of digitalis and causes nausea, vomiting and diarrhoea, as well as sometimes resulting in xanthopsia (jaundiced or yellow vision) and the appearance of blurred outlines (halos), drooling, abnormal heart rate, cardiac arrhythmias, weakness, collapse, dilated pupils, tremors, seizures, and even death. Bradycardia also occurs. Because a frequent side effect of digitalis is reduction of appetite, some individuals have used the drug as a weight-loss aid.

Slide29

Artemisia

absinthium

Artemisia

absinthium

(

absinthium

, absinthe wormwood, wormwood, common wormwood, green ginger or grand wormwood) is a species of Artemisia, native to temperate regions of Eurasia and Northern Africa and widely naturalized in Canada and the northern United States.

It is grown as an ornamental plant and is used as an ingredient in the spirit absinthe as well as some other alcoholic drinks.Artemisia absinthium contains thujone, a GABAA receptor antagonist that can cause epileptic-like convulsions and kidney failure when ingested in large amounts.Edgar Degas Dans un café ”l'Absinthe” 1873

Slide30

Tansy

Tansy (

Tanacetum

vulgare

) is a perennial, herbaceous flowering plant of the aster family, native to temperate Europe and Asia

.

Tansy was used to treat intestinal worms, rheumatism, digestive problems, fevers, sores, and to “bring out” 

measles. During the Middle Ages and later, high doses were used to induce abortions.

Slide31

Mycotoxin

The term 'mycotoxin' is usually reserved for the toxic chemical products produced by fungi that readily colonize crops

.

One mold species may produce many different mycotoxins, and the same mycotoxin may be produced by several species

.

Aflatoxins

. The aflatoxins were isolated and characterized after the death of more than 100,000 turkey

poults (turkey X disease) was traced to the consumption of a mold-contaminated peanut meal. The four major aflatoxins are called B1, B2, G1, and G2 based on their fluorescence under UV light (blue or green) and relative chromatographic mobility during thin-layer chromatography. Aflatoxin B1 is the most potent natural carcinogen known and is usually the major aflatoxin produced by toxigenic strains.

Slide32

Forensic Toxicology

of

Ethyl Alcohol

According to statistics of the National Highway Traffic Safety

Administration, 17 126 persons were killed in alcohol-related accidents in

1996. This constitutes 40.9% of all people killed in traffic accidents that year. If one counts only those deaths in which one or more persons had a blood alcohol content above the legal limit of 0.1% at the time of the accident, the figure of alcohol-related deaths is reduced to 13,395, or approximately 32% of all fatal crashes. In comparison, approximately 15% of total road deaths in Great Britain involve accidents in which one or more people have a blood alcohol content (BAC) over the legal limit of 0.08.

Slide33

The ethanol concentration exceeds 1‰ in 50% of drivers responsible for accidents; in about 30-40% of them the ethanol level exceeds 1.5 ‰

Slide34

The insobriety condition at the moment of accident may be demonstrated using blood or respiratory air tests

Evidence

methods

to

determinate of the ethanol in blood :head-space gas chromatogrphyStationary analyzers with spectrophotometric detector IR

Alkometr

A2.0

Slide35

dr hab. G. Buszewicz (Lublin)

Slide36

Alcohol has been a global companion for many hundred of years

One important thing to remember about alcohol is that it is a drug, and people get addicted to it.

It's

known as

alcoholism

and people who suffer from it are called

alcoholics. The truth is, alcoholism is a disease, and it can be very, very hard for alcoholics to stop drinking. So why do people start drinking to begin with?

Slide37

1)

"Drinking helps me deal with my problems.„

2

)

"Drinking helps me have a good time

.„

3)

"Drinking makes me high and happy.„4) "Drinking is cool.„5) "Drinking keeps me warm when it's cold out.„6)”I can't have a drinking problem, because I only drink beer and wine, not hard liquor.„7)"I only drink because all my friends drink too."

Slide38

Slide39

State after

consuming

ethanol

occurs when the alcohol content in the body is or leads to:1) blood alcohol content from 0.2 to 0.5 ‰

or 2) from 0.1 mg to 0.25 mg of alcohol in 1 dm3 of breathDrunk state occurs when the alcohol concentration in the body is or leads to: blood alcohol content above 0.5 ‰ of alcohol or the presence of exhaled above 0.25 mg of alcohol in 1 dm3

Slide40

Erik M. P. Widmark

(1889-1945) was among the first researchers to study in a systematic way the absorption, distribution, and elimination of ethanol in the body; in addition, he formulated his results in mathematical terms.

Widmark's

research during the first decades of

last

century paved the way for innovative traffic safety legislation that stipulated punishable limits of alcohol in the blood of a person driving a car.

Slide41

ex-post

‰

t

0

t

C-max

(ok. 30 – 60 min)

C

max

A = c

0

·

W

·

r

β

60

= 0,07 – 0,28 (0,1-0,2) ‰/h

[g]

[kg]

[

‰

]

c

0

=

C

t

+

β

60

x

t



~ 0,55 (0,47÷0,64)

distribution

coefficient



~ 0,68 (0,51÷0,85)

Widmark

equation

coefficient of alcohol elimination from the body

Slide42

Retrospective calculations can be performed in cases which meet the

the

following conditions:

1) the concentration of alcohol in the blood (or breath) during the first study

must

be

higher than 0.4 ‰,2) the duration of the event to the first study can not be longer than 5-6 hours3) At the time the event suspect must be in the elimination

phase of alcohol,4) the suspect should not consume alcohol between the event and studies of concentration of alcohol.

Slide43