Chapter 9 – Toxicology
Metabolism (biotransformation) – This occurs in the liver. As a drug reaches
the liver it is broken down into metabolites. The first breakdown produces the
primary metabolite, which then may be further broken down. Heroin’s primary
metabolite is morphine. Metabolism breaks down substances into less harmful
products which are easier to eliminate in urine, such as ionic salt forms.
Metabolism may be so quick that toxicologists often look for evidence of known
metabolites rather than the original drug form.
Elimination – This can happen through breathing (volatile chemicals), sweating
(water soluble drugs) but most typically through a person’s urine.
Finding toxins in sufficient quantities requires specialized tests and during autopsies.
Samples are often collected from places where toxins are more likely to accumulate.
These include the tissue around an injection site, the liver, stomach, blood and urine.
1. Blood – drugs and metabolites accumulate in blood and blood levels give an
indication of lethality and toxicity.
2. Urine – Most often used in workplace drug testing. Many drugs accumulate in
the kidneys, as they are located close to the liver. Urine levels do not correlate
as well as blood levels, as they are influenced by how much water is drunk and
how much urine is produced.
3. Stomach contents – These can be pumped out of survivors, or removed during
autopsy. This is typically done if a death is thought to be due to ingestion of a
toxin, but stomach levels will not correlate as well as blood levels.
4. Liver – This is the body’s main site for toxin metabolism, so toxins can
accumulate here. The liver also produces bile, which can also be tested for
toxins, especially opiates. The liver shows what may have been in the blood
hours before, whereas the bile retains evidence of toxins for several days.
5. Vitreous humor – the liquid/jelly filled part of the eye. It is resistant to
putrefaction and water-soluble substances dissolve in it. Levels in the vitreous
humor are balanced with the blood, but there is a time delay of 1-2 hours, so
quantities found here reflect what was in the blood 1-2 hours earlier.
6. Hair – Can be used to create a timeline for drugs and heavy metals which are
trapped within the hair shaft.
7. Insects – as insects feed on the dead tissues they accumulate toxins within
their own tissues, so they may also be tested.
Based on test results a toxicologist can identify the drug, the route of entry and
determine if the concentrations present are significant. Concentrations are usually
highest at the point of administration:
Ingested toxins highest in the stomach.
Inhaled toxins highest in the lungs
Injected toxins highest in the tissue at the injection site
IV drugs enter directly into the blood and are quickly dispersed but are
usually at low levels in the liver and stomach.
Blood level of a toxin is categorized as:
Normal – found in the general population
Therapeutic – level bringing about the most beneficial effect, typically for
Toxic – may cause harm, nausea, vomiting, death
Lethal – at this level the drug will consistently cause death. The LD50 test
determines the level at which a drug will cause death (Lethal Dose) in 50% of
the people taking it at that dose.
These levels are open to interpretation and individuals react differently based on
their overall health, age, sex and tolerance levels brought about by previous
Poisoning can be either acute or chronic. Acute poisoning is quick and intense,
whereas chronic poisoning can have been occurring at low levels over a long period of
time. Some heavy metal poisons and certain drugs can accumulate in the hair. Hair
follicle cells are eventually incorporated into the growing hair shaft, which grows
around ½ inch per month. A level of poison in hair of different lengths gives a
timeline for the poisoning.
Sometimes a person may die due to a combination of drugs. Often each drug on its
own is not at a lethal level, but the combined effect is lethal. This is known as
synergism - when someone exhibits magnified effects from a combination of drugs
(the whole is greater than the sum of the parts). With so many legal and illicit drugs
on the market it is very important to look at the synergistic effects of drug
combinations when determining cause and manner of death.
Tolerance to a drug occurs when increasing doses are required to keep the same
level of effect on a person. It is very common in people who continually abuse the
same drug. Initially someone may get high from a 10mg dose of methamphetamine,
but after several days they may find they need to take 20mg to achieve the same
effect, and several days later this may increase to 30mg and so on. This becomes an
issue when someone tries to withdraw from the drug and for some drugs, such as
barbiturates withdrawal must be done slowly as sudden withdrawal can be fatal.
Because tolerance means an individual can take ever increasing quantities of a drug
without having a dangerous reaction a person’s drug history needs to be examined if
they have died from drug usage. High levels of a drug do not necessarily means that
the drug was the cause of death.
Some drugs show phenomena known as reverse tolerance. Marijuana users often
state that they get a more heightened effect from the same level of usage over
time. This may be due to the fact that THC (tetrachydrocannibinol) accumulates in
the body over time (does not metabolize), so regular use actually increases the
concentration in the body.
Addiction – This is a physical process. Not all drugs are addictive. Those that are
cause a biochemical change in the body as a means of tolerating the drug. These
biochemical changes mean that the body now requires the drug on a regular basis and
without it an extreme craving sets is. This craving takes over and becomes the focus
of a person’s life. Personal hygiene may be neglected, crime is often committed to
fund the purchase of the drugs and without them withdrawal symptoms develop.
These may include sleeplessness, nausea, hallucinations, headaches and joint pain.
Withdrawal can last days or weeks.
Dependence – This is a psychological phenomenon. There are no biochemical changes;
however users can still develop drug cravings. The biggest difference is that failure
to take the drug does not produce withdrawal.
Some drugs can cause either addiction or dependence, depending on the dosage
Alcohol is probably the most commonly abused and socially acceptable drug. It leads
to loss of coordination and lack of judgment.
Ethyl alcohol, or ethanol (CH3OH) is distilled from a variety of foodstuffs and is a
product of fermentation. Ethanol is the active ingredient in all liquor, wine and beer.
Alcohol concentrations are measured in proof, which is 2x the volume % of alcohol.
100 proof liquor is 50% alcohol by volume. In beer and wine alcohol is measured in
volume percent. Wine is around 12% and beer around 5%.
Alcohol is a central nervous system depressant and acts as a mild tranquilizer. It is
also a neurotoxin, so it kills nerve cells. Around 1 ounce of alcohol is estimated to kill
around 10,000 nerve cells.
During the prohibition era the federal government attempted to ban alcohol, leading
people to seek alternatives such as methanol or isopropyl alcohol, both of which
destroy optic nerves and cause blindness.
Because of the depressant properties of alcohol there are federal and state laws
governing the amount of alcohol a person may drink before they are considered
legally drunk and incapable of operating a motor vehicle. Because the levels of alcohol
in the brain cannot be measured toxicologists use blood alcohol levels to infer relative
levels in the brain. These levels are referred to as blood alcohol concentration or
BAC, or breath alcohol concentration or BrAC. Most breathalyzers measure BrAC,
which is then converted to BAC.
BAC is measured in weight/volume percent, or the number of grams of alcohol
present in 100ml of blood.
0.03% = 1 beer. This produces little effect on motor skills, but may produce a “buzz”
0.03-0.08% - coordination, judgment and reaction time all impaired.
>0.12% - nausea and vomiting
0.15% - balance is seriously compromised. This is equivalent to ½ pint of liquor in the
0.25% - coma
0.3-0.4% - deep coma and death
The legal limit is usually 0.08%, except for commercial drivers, whose legal limit is
0.04%. Sweden has one of the lowest legal limits at 0.02% and many other countries
set their limit at 0.05%.
Operating a vehicle means “implied consent”, which in turn means that if stopped you
must submit to a breathalyzer or alcohol test or lose your license (6 months – 1 year).
This law was challenged in the case of Schmerber vs California. Schmerber had
blood samples removed against his will by a physician following a motor vehicle
accident. His case argued that his 5th amendment rights against self incrimination had
been violated, however the Supreme Court ruled against him, as they said the law only
applied to testimonial evidence, not physical evidence. ++++
The concentration of blood alcohol depends upon the rate of absorption and
elimination by the body. Alcohol is absorbed in both the stomach and small intestines.
The rate of absorption depends on the concentration of the drink and the contents
of the stomach, as well as a person’s weight, age, sex and overall health. Food in the
stomach competes with alcohol for absorption and foods high in carbohydrates slow
the absorption of alcohol the most, because their rate of absorption is also slow.
Beer is absorbed more slowly because it is high in carbohydrates. Alcohol will
accumulate in all parts of the body, but levels are greater in more watery areas and
less in areas of bone, fat or hair.
Alcohol taken on an empty stomach is absorbed quicker and has a greater effect.
Alcohol appears in the blood within minutes of consumption. It eventually reaches the
brain where it acts on the outer surfaces that affect motor coordination. If the
levels are high enough it will penetrate to the inner brain and affect seeing, talking,
balance, judgment and inhibitions. If it continues more deeply into the brain tissue it
then affects the autonomic nervous system which includes involuntary functions such
as breathing and heart rate. Toxicologists frequently have to determine blood alcohol
concentrations for autopsy purposes and if there is insufficient blood available they
may use fluids from the spinal column, vitreous humor or urine to obtain BAC
Alcohol is metabolized by the liver into acetaldehyde and then acetic acid by a series
of oxidation reactions controlled by the enzyme alcohol dehydrogenase. The acetic
acid is eventually broken down into H2O and CO2. Alcohol can also be eliminated via
the breath as it is a volatile chemical and it passes easily from the blood stream into
Field Sobriety Test – the first test given when stopped for DUI. It is designed to
test the effects of alcohol on the balance centers of the brain. In states that
recognize the field sobriety test it is admissible in court as evidence. Similar results
can be obtained from someone under the influence of drugs, so if a breath test
indicates a subject wasn’t drinking then the field sobriety test can be used as
evidence of impairment by other means.
A drug is defined as a substance designed to have a specific physical and/or
emotional effect on a person or animal. Drugs produced by pharmaceutical
companies for a particular disease or disorder are called licit drugs and legally must
have a recognized medical use as defined by the US Food and Drug Administration
(FDA). Illicit drugs, or controlled substances, or abused drugs, may be licit drugs
taken for purposes other than those for which they were originally developed. An
example of this would be methamphetamine, which was originally legitimately
marketed as a stimulant to counter depression. Steroids are other licit drugs that
are used fraudulently or inappropriately by athletes. Other illicit drugs have no
recognized medical purpose, such as synthetic PCP, cocaine or heroin.
It is illegal to possess, grow or sell illicit drugs with no medical purpose. Federal law
regulates illicit drugs as part of the Federal code, Title 21, Chapter 13 (The
Controlled Substances Act). Illicit drugs are termed controlled substances and are
put into one of five schedules or categories. Drugs in the same schedule have the
same penalties for possession or distribution. Penalties may increase as the amount of
the drug increases.
Congress passes all federal laws and so the House and Senate decide which illicit
drugs will be controlled (scheduled) and to which schedule they will be placed. To do
this they must answer 2 questions:
1. Does the drug have a legitimate medical use in the USA?
2. What is its potential for abuse?
The first question is guided by the FDA. For the second question considerations such
as addictiveness, physical and psychological dependency, cost and availability must be
taken into account.
Schedule I – high potential for abuse, no medical use. Heroin; marijuana; LSD
Schedule II – high potential for use, medical use with severe restrictions, potential
for physical & psychological dependence – opium, cocaine, methadone, PCP,
Schedule III – less potential for abuse, currently accepted medical use, low physical
dependence – steroids; codeine preps.
Schedule IV – as for schedule III, except risks are lower – phenobarbitol; diazepam;
Schedule V – low abuse potential. Includes some OTC cough preparations containing
These were probably the most popular illicit drugs in the 1960’s and 70’s, with
barbiturates being the most popular. Alcohol is a depressant as it suppresses the
CNS. Opiates and tranquilizers are also depressants/downers.
Barbiturates – come from barbituric acid and are used as hypnotics/sleeping
pills. The only barbiturate in common use today is Phenobarbital, which is
widely used as an anti-seizure medication in epileptics. When combined with
alcohol they are particularly dangerous and may lead to coma and death. The
Dilli-Kopani test is used to test for barbiturates. Pentobarbitol and
penththiobarbitol are very powerful depressants and are used for euthanasia
and lethal injection. They are highly addictive and sudden withdrawal or “cold
turkey” can lead to death. Janis Joplin and Jimi Hendrix both died from
overdoses of barbiturates.
Narcotics – these are powerful sleep inducing CNS depressants and
analgesics (pain relievers) and usually refer to opiate substances derived from
the opium poppy (Papaver somniferum). They produce euphoria, lethargy, coma
and death from respiratory asphyxia. All are highly addictive. Opiates depress
the respiratory center of the brain and can lead to a user slipping into a coma
and stopping breathing.
Morphine & codeine are natural opiates, whereas heroin is di-
acetlymorphine and is produced synthetically by combining morphine with
acetic anhydride or acetyl chloride. Heroin is ten times stronger than the same
dose of morphine. In living subjects the Marquis test is used to detect
opiates. Heroin is rapidly broken down into mono-acetylmorphine and eventually
morphine, so it is not always possible to tell if someone took heroin or just
morphine. Fluid from the vitreous humor often provides a better indication due
to the time lag. Heroin sold on the streets is a white or brown powder between
3-10% pure mixed or “cut” with substances such as sugar. It is then mixed with
water, heated and filtered then injected intravenously. Someone who dies from
heroin abuse typically shows evidence of pulmonary edema (water in the lungs)
as talc crystals and cotton fibers accumulate in the lungs, as both of these are
used to “cut and filter” the heroin. Methadone is a synthetic heroin substitute
used for people trying to withdraw from heroin abuse. Oxycontin is also a
The most common are amphetamines and cocaine. They increase alertness, lessen
fatigue and suppress appetite. Continuous use leads to paranoia, aggression,
irritability, fatigue and depression. They also cause strong psychological dependence.
Continued use leads to tachyphylaxis, which means that the body becomes used to
them and higher doses are needed to induce the same effect. Tachyphylaxis leads to
overproduction of the enzymes needed to metabolize the drugs, so as the drug is
consumed it is broken down quicker.
Amphetamines and methamphetamine are widely abused and easily produced.
Both drugs have legitimate medical uses as stimulants to relieve lethargy and
depression, but because of their abuse potential they are rarely produced for licit
purposes and are made in clandestine “meth labs”. Meth was also known as “speed” and
high doses are fatal. Methamphetamine is usually made using the OTC cold
preparation pseudoephedrine, ammonia and lithium, extracted from batteries.
Cocaine is a naturally occurring substance from the Erythoxylon coca plant, not the
same as the cocoa plant from which chocolate is derived. It is found predominantly in
the Andes Mountains of South America and the center for cocaine production is
Columbia. It has anesthetic properties similar to novacaine (used in dental
procedures) and benzocaine (used to treat sunburn). It was originally chewed by
Andean farmers as a stimulant during arduous farming. In the early 20th century it
was the main ingredient in “elixirs” sold as miracle cures by traveling salesmen in
wagons, but once it was banned it was replaced by caffeine in many of these
preparations. Cola drinks originally contained cocaine but now contain caffeine as the
Cocaine is extracted from the leaves by dissolving them in hot alkaline water then a
second solvent containing hydrochloric acid is added to precipitate the cocaine
powder in to a fine “snow” like substance. It is then cut with an inert powder to
around 20-50% purity. It can be ingested by snorting, which is less effective, but in
the 1980’s crack cocaine appeared, which is a rock form which is smoked and is highly
physically addictive and typically carries much more severe penalties than the flake
form. Cocaine is metabolized to methylecgonine and benzolecgonine. These are
detectable in urine tests for up to 3 days after the last use and are found by
immunoassay or the Scott color test.
These alter perception and mood and cause delusions and hallucinations. Delusions are
false beliefs and hallucinations are sensory experiences that can be visual, auditory,
olfactory, tactile or taste. The most common hallucinogens are either natural plants
such as marijuana, peyote or mushrooms, or lab made such as LSD, PCP.
Marijuana – a cannaboid, from the plant Cannabis sativa, and the active ingredient is
THC (tetrahydrocannabinol). Levels of THC in marijuana (dried leaves & flowering
parts) are from 2-6% compared to levels of 12% in hashish oil, the oily resin extract
from the flowering parts. Hashish is made by mixing marijuana with a solvent. Once
the solvent evaporates the semi-solid cake or hashish is left which is smoked in a
pipe. The roots, stems and seeds do not contain appreciable levels of THC. Although
not a true hallucinogen compared to LSD and mushrooms it is classified as one
because it doesn’t fit into any of the other categories.
THC metabolizes in to 9-carboxy-THC which is detectable in urine up to 2 months
after the last use. The Duquenois-Levine test shows a purple color change in the
presence of cannaboids. Confirmatory testing is by mass spectrometry and gas
chromatography gives a quantitative reading, unlike the qualitative color test.
In recent years marijuana has been reported to have some medical uses for the
treatment of glaucoma and helping with the side effects of chemotherapy in cancer
patients. It does not have FDA approval however people may apply to courts for an
order to obtain medical marijuana in the form of tablets containing marijuana
Peyote is a Mexican cactus with the active ingredient mescaline, which is an alkaloid
hallucinogen. The outer leaves are covered in bumps called peyote buttons, which are
peeled to reveal cotton like tufts. The buttons are eaten but are hard to digest and
can cause nausea.
Mushrooms are not illegal as of this writing, unlike peyote and marijuana. The active
ingredient in hallucinogenic mushrooms is psilocin or psilocybin, and these are
detected by the color change test, Van Urk’s reagent (turns purple) or Fast Blue B
LSD – lysergic acid diethylamide is probably the most potent hallucinogen. As little as
25micrograms produces effects lasting 12 hours. The most common form is called
blotter acid, where the LSD is diluted with solvent and dripped onto blotter paper
and cut into tiny squares or microdots. It has also been found in body decals and is
easily absorbed through the skin. Hallucinations are vivid and can alter perception
leading to harm. It is screened for using the Van Urk test.
PCP – phencyclidine (angel dust). A powerful hallucinogen which is often mixed with
marijuana and smoked. It remains in the urine up to 1 week after the last use.
GHB – gamma-hydroxybutyrate (depressant)
Rohypnol – flunitrazepam (depressant)
Ecstasy – 3,4-Methylenedioxymethamphetamine (hallucinogen)
Ketamine – ketamine hydrochloride (depressant & hallucinogen)
All cause compliance, lack of judgment, sedation and amnesia while under the
influence, leading to their use as date rape drugs.
Recreational use is a lottery due to variable quality and purity from cutting with talc
or other drugs. This means that users really don’t know what they are ingesting and in
Ecstasy is an amphetamine and is detectable during routine drug screening. The
others can be detected by GC/MS.
This includes sniffing or “huffing” of volatile chemicals such as glue, gasoline,
naphthalene (mothballs), toluene (paint thinner, nail polish, dry cleaning fluids),
trichloroethylene (correction fluids).
Inhalation leads to giddiness, euphoria, dizziness, headache, slurred speech, vomiting.
Permanent damage to the brain, kidneys, liver and heart is not uncommon. The
gases themselves are hard to detect by toxicology as they break down quickly so
signs are usually looked for in organ damage.
These are hormones that are found naturally in the body in small amounts. In larger
doses they cause muscle growth, increased strength and improved reflexes, and as
such their abuse amongst athletes is becoming epidemic. However, they also cause
hair loss, impotence, liver damage and aggression.
Cyanide – metabolic poison, damages cellular processes.. Causes blood to appear
bright, cherry red in color.
Strychnine – derived from plants and used in some rat poisons. Very bitter taste,
hard to disguise. Causes severe convulsions – opisthotonos - only head & heels touch
floor and back is arched, leading to asphyxia.
Death Cap/Death Angel mushrooms – contain amantin and phalloidin toxins. Only one
needed to cause death. Severely damages liver tissue.
Ethylene Glycol – Antifreeze. Often drunk by alcoholics who cannot get
ethanol/drinking alcohol. Breaks down in to oxalic acid leading to oxalate crystal
formation in the brain and kidneys, causing death.
Oxalic acid – found in raw rhubarb. It is an irritant in the GI tract. The oxalic acid is
absorbed in to the blood and reacts with calcium to form calcium oxalate leading to
cardiac arrest and kidney damage.
Heavy Metals – includes arsenic, mercury, lead, antimony, thallium. All cause
gastrointestinal injury and damage to kidneys, liver, brain and nerves.
Insulin – Large doses dramatically drop blood sugar levels, causing brain damage and
Succinyl choline – injectable muscle paralyzer, leads to asphyxia. Is one of 3 drugs
used in lethal injections.
Corrosive Chemicals – such as lye, hydrochloric acid, sulfuric acid. Cause burning of
mouth, esophagus and stomach, leading to bleeding, shock and agonizing death.
Carbon Monoxide – attaches to hemoglobin, forming carboxyhemoglobin, which blocks
the uptake of oxygen. Typical signs are bright red blood. A saturation in excess of
50% is usually fatal. Fire victims should have CO in their blood if they were alive
when the fire started and breathed in the combustion fumes.
Chemical Analysis Methods
The initial tests done are presumptive, and a positive result is then followed up with a
confirmatory test. Common presumptive tests include:
Color tests – used for classes of chemicals. Reagent is added to blood, urine or tissue
that produces a color change.
Immunoassays- uses antigen/antibody binding. Reagent is the antibody that will react
only with a specific antigen being sought. Used in urine analysis to detect acid
compounds such as barbiturates and aspirin, and also to detect opiates, cocaine and
Thin Layer Chromatography (TLC) – separates compounds based on their movement
through an absorbent material combined with a solvent. Compounds are then checked
against known standards.
Gas Chromatography – separates based on a compounds ability to move through an
inert gas. It rapidly separates mixtures. The mixture is injected into one end of a
column, heated and vaporized. It then flows with the gas to a detector. Different
compounds reach the detector at different times based on their size and speed. A
visual chromatograph is produced. Used to detect alcohols and as an alkaline screen,
i.e. substances that dissolve in alkaline solutions such as tranquilizers and
UV Spectroscopy – different compounds absorb or reflect light in differing amounts
and wavelengths. Compounds are exposed to UV light at different wavelengths and
the degree of absorption is measured and checked against standards.
Confirmatory tests should be sensitive and specific so as to exclude any other
possible chemicals. The most common confirmatory tests are:
Mass Spectrometry – the compound is bombarded with high-energy electrons that
break up the compound. The fragments pass through a magnetic field and are
separated according to mass, producing a visual fragmentation pattern, which can be
checked against known standards. MS is often used together with GC, with the GC
test coming first and the gaseous compounds it separates are fed directly into the
Infrared Spectroscopy is similar to MS but used infrared instead of electrons.