`FORENSIC TOXICOLOGY

o the study and practice of the application of toxicology to the purposes of

the law;
identification & quantifying of a drug, poison or substance in human
tissue
results interpretation
o Toxicology results are correlated with medical history, the autopsy findings
and the circumstances leading up to or surrounding the death, so as to
determine whether a drug was the cause of death, a contributing factor, or
played no role.
o Poison - any substance taken into the body that interferes with normal
physiological functions.
o Poisoning - the state produced by introduction of a poison into the body.
Poisoning
Poisoning is very common, most poisonings being accidental or suicidal in
nature (homicidal is now rare)
Majority of the accidental group = children
Two main types of poisoning;
o those in the home from medicinal substances and domestic
chemicals
o those in agriculture and industry from a wide range of toxic
substances.
Types of toxic substances
Alcohols
Toxic gases
Insecticides
Metals
Analgesics
Drugs of abuse
Types of

Sedatives and
hypnotics
Stimulants
Anticholinergic
drugs

Psychedelic
drugs
Plants
Snake venoms
Herbicide

poison
target organ (liver, kidney, haematopoietic system, etc)
use (pesticide, solvent, food additive, etc.)
source (animal and plant toxin)
effects (cancer, mutation, liver injury, etc)
chemistry (aromatic amine, halogenated hydrocarbon)

Routes of Administrations
Ingestion (gastrointestinal tract)
Inhalation (lungs)
Topical (skin)
parenteral (intravenous)
Toxic agents elicit greatest effect and produce most rapid response
when given by IV
Tolerance
Definition: a state of decrease responsiveness to a toxic effect of a
chemical resulting from prior exposure to that chemical or to a
structurally related chemical.

Example: carbon tetrachloride produces tolerance to itself by

decreasing formation of the reactive metabolite that produces liver
injury.

Idiosyncrasy
Definition: a genetically determined abnormal reactivity to a chemical.
The response observed is usually similar to that observed in all
individuals (may take the form of extreme sensitivity to low doses or
extreme insensitivity to high doses of the chemical).
Example: Prolonged muscular relaxation and apnoea after a standard
dose of succinylcholine.
Drug Interactions
Mechanism of drug interaction: alterations in absorption, protein
binding and biotransformation or excretion of one or both of the
interacting drugs.
The response may be increased or decreased because of the
toxicological responses at the site of action.
Example: carbon tetrachloride and ethanol are hepatotoxic compounds,
but together they produce much more liver injury than their individual
effects on the liver.
Toxicology
Definition: study of chemical or physical agents that produce adverse
responses or effects in the biological system with which they interact.
These responses span a broad physiological spectrum ranging from minor
irritation to liver or kidney damage or permanent disabilities e.g; lund ds,
kidney failure or cancer.
Toxicologists perform 1 or both of 2 basic functions of toxicology:o To examine the nature of adverse effects produced by chemical or
physical agents
o To assess the probability of their occurrence.
Toxicologists role is to examine drugs and poisons in biological specimens
Forensic chemistry
Chemists role is to examine: Seized drugs
Accelerants/ explosive
residues
Glass/ paint fragments

Soil specimens from

footwear
Inks (questioned
documents)

Poisoning by common drugs and toxic substances

Alcohol
Paraquat
Carbon Monoxide
Organophosphate
Paracetamol
Drugs of abuse

Alcohol

Found in beer, wine & other alcoholic beverages

A clear, colourless & sweet smelling liquid
Properties: loss of equilibrium, euphoria & loss of inhibition
Drunk drivers more prone to RTA
Legal limit
o 35 microgram alcohol per 100 ml of breath
o 80 mg alcohol per 100 ml of blood (7.4 mmol/L)
o 107 mg alcohol per 100 ml urine
Pathological effects alcohol abuse
Alcohols: a group of organic liquids which have a particular chemical
grouping (OH). It is named according to the length of the carbon
backbone.
o Methanol (methyl alcohol)
o Propanol (propyl alcohol)
o Ethanol (ethyl alcohol) =
o Butanol (butyl alcohol)
"alcohol" !
o
Ethanol is by far the commonest alcohol.. Alcohol is used throughout
most societies to affect mood and to alleviate discomfort. It is an
addictive drug.
In USA the third largest health problem, is on the increase, reduces life
expectancy by 12 years.
Causes: serious problems in 1m drinkers, 500 deaths under 25.
Assoc. with: 1/2 million hospital admissions, 17 000 psychiatric
admissions, 80% fire deaths, 65% serious head injuries, 50% murders,
40% road traffic accidents, 30% fatal accidents, 30% domestic
accidents.
Contibutes to: 33% divorces, 33% child abuse cases.
o
o Complications of Excessive Alcohol Intake
Physical, psychological and social complications are not confined to
alcoholics, they can affect any individual who drinks heavily for a prolonged
period.
o
a) Physical
o GI
o Oesophageal varices a/w portal hypertension, UGIB,
T
stomach, small intestine. Impairs the nervous supply
of the bowel and absorption of many vital nutrients.
Causes oesophagitis, gastritis, duodenitis, peptic
ulcer, small bowel malabsorption acute and chronic
pancreatitis
o Liv
o fatty liver; alcoholic heptatitis; alcoholic cirrhosis with
er
micronodular lesions
o CV
o hypertension; cardiomyopathy and wet beri-beri
S
(thiamine deficiency)
o CN
o cerebral atrophy (alcoholic dementia); WernickeS
Korsakoff Syndrome due to thiamine (vitamin B
deficiency); cerebellar degeneration, central pontine
myelinosis, and peripheral neuropathy
o Me
o imbalance of metabolism of many bodily compounds
ta
including glucose, uric acid, phosphate, magnesium,
bo
potassium, fats and proteins

lic
ef
ec
ts
En
do
cri
ne
ef
ec
ts
Ot
he
rs

male impotence; female infertility

a. Severe bruising of various ages due to frequent, unprotected

clumsy falls. Typical distribution is over bony prominences of
limbs, torso & head
b. Microcytic, hypochromic anaemia
c. Infections: lobar pneumonia, bronchopneumonia

o
b) Psychological
o
Anxiety, depression, high suicide risk, dementia, pathological
jealousy, alcoholic hallucinosis, sexual dysfunction
o
c) Social
o
Marital & family problems, including domestic violence
o
Work problems, unemployment. Road accidents and crime.
o
o Cause of death in chronic alcoholics
o Fairly equal distribution between trauma, natural disease, acute
intoxication and other alcohol-related disease.
o
o 1. Trauma. The largest group (26%).
Fire deaths were the most
Road traffic accidents
common.
(pedestrians),
Drunken falls were frequently
Drowning,
followed by fatal head injury.
Railway line accidents,
Murder,
Accidental poisonings, and
Accidental hangings.

2. Incidental Natural Disease (25%).

IHD, cerebral haemorrhage, COAD & malignancy.

3. Alcohol Related Disease (22%).

- Bronchopneumonia and lobar pneumonia

- Cirrhosis of the liver

- Ruptured varices or hepatic failure. {Many of these deaths occur in

hospital and are excluded from forensic practice.}

- Alcoholic cardiomyopathy and

- pancreatitis are other rarely reported causes of death.

4. Acute Intoxication (24%).

-Simple intoxication causing respiratory depression was responsible for 72

cases
-The BAC was 261-612 mg% (average 450).
-Those with a BAC below 318 mg% had co-existing IHD, COAD or cirrhosis.
-Inhalation of vomit was the primary cause of death in 18 cases.
-The BAC was as low as 152 mg% in these cases.

Possible mechanisms of death from simple intoxication:

1. + Simple depression of the respiratory centre in lower brain stem by
alcohol itself.
2. + Inhalation of vomit due to coma.
3. + Postural asphyxia (obstruction of the upper airway by the swallowed
tongue during coma.

5.'Obscure' cause of Death

-Many cases show fatty liver only and no convincing cause of death.
-Death can be attributed in these cases to the numerous severe metabolic
and biochemical disturbances caused by alcoholism.
-ECG changes are common in alcoholics and death may be due to a
disturbance in the electrical rhythm of the heart.

Conce
ntratio
n
(mg %)
10 50

No obvious impairment
Euphoria, decreased inhibition, decrease in judgement
& control, decrease in fine motor control & start of
sensory motor impairment
Emotional instability, impaired perception & memory,
reduced visual ability, impaired balance

30
120

90
250

180
300
350
500

Common effects

Dizziness, diplopia, decreased muscular coordination,

slurred speech
Coma, anaesthesia, severely depressed reflexes,
respiratory & circulatory collapse & death

CO Poisoning
Carbon monoxide, or CO, is an odorless, colorless gas that can cause sudden
illness and death.
odorless, invisible, tasteless & non-irritating (silent killer)
CO is found in combustion fumes, such as those produced by
cars and trucks,
CO from these sources
small gasoline engines,
can build up in enclosed
stoves,
or semi-enclosed spaces.
lanterns,
People and animals in
burning charcoal and wood, and gas ranges and
these spaces can be
heating systems.
poisoned by breathing it.


Leading cause of accidental poisoning deaths in the United States
Most fatalities result from fires, malfunctioning stoves, exhaust systems,
heaters, suicide attempts (70% of deaths = suicide)
Impairs oxygen delivery and has its most lethal effects on organs requiring
high levels of oxygen, i.e. the brain and heart
toxicity: due to displacement of oxygen with resulting failure to adequately
oxygenate the tissue
Binds reversibly to hemoglobin much more avidly than oxygen (200-250
times more avidly) leading to high levels of carboxyhemoglobin/ CO = 300
times affinity for Hb
It also binds to myoglobin with an even greater affinity than to hemoglobin
symptoms= headache, nausea, vomiting, convulsions, respiratory failure,
coma and death.
Suicide : tube leading from exhaust pipe into the car passenger
compartment.
Autopsy: a cherry pink hypostasis (discoloration to the skin), cherry pink
grey matter, dark red, carboxy haemoglobin.
Populations at risk for mortality are those over the age of 75, those with
underlying cardiopulmonary disorders, neonates and the fetus in utero
Pathology in brain
White matter demyelination
Edema and necrosis bilaterally in the globus pallidus, caudate nucleus and
cerebellum
Treatment
100% oxygen
Hyperbaric oxygen treatment remains controversial

Paracetamol
Accidental and suicidal poisonings
Accidental in children
Suicidal in adults
In overdose (>150mg/kg) can cause acute centrilobular hepatic
necrosis which is often fatal
24 - 48 hours = raised PT, serum bilirubin,
raised liver enzymes
Peak hepatotoxicity : 72 - 96 hours after ingestion (vomiting, right
upper quadrant pain, lethargy, jaundice, coagulation disorders,
hypoglyvaemia, confusion and coma.
Death = 4 - 18 days (from fulminant hepatic failure occur days post
ingestion).
Treatment
o reduce absorption (gastric lavage, activated charcoal)

oral methionine (glutathione precursor)

I/v N-acetylcysteine (promotes hepatic glutathione synthesis)

Paraquat
The number of accidental cases of poisoning is small relative to instances
of suicide.
While the vast majority of poisoning cases are due to swallowing,
a small number of fatal cases of accidental paraquat poisoning via the
skin have been reported when liquid concentrates (200 g/litre) have been
applied in order to kill body lice
A few other fatal and non-fatal cases have been reported following skincontamination
most frequent route of poisoning has been ingestion.
There is no evidence of fatal poisoning as a result of inhalation.
The minimum lethal dose of paraquat is stated to be about 35 mg/kg
body weight for human beings
Toxicity results from lung injury
1-3 days = intense pain in the mouth and pharynx, with inflammation /
ulceration of the mucous membrane.
2-4 days = symptoms of renal and hepatic failure
3-14 days = paraquat is specifically taken by lung tissue. Intra-alveolar
oedema and haemorrhage followed by epithelial proliferation, focal
atelactasis and massive alveolar fibrosis.

- Treatment:

1. immediate
gastric lavage

2. Fullers earth
(300 gm in tha
stomach)

3. forced diuresis
(intravenous frusemide)
o
o

Clinical and pathomorphological data relating to fatal paraquat poisoning

Cases of fatal poisoning can be sub-divided into cases of:

(a) acute fulminant poisoning from a massive dose leading to generalized
systemic poisoning and death from a combination of acute pulmonary
oedema, oliguria, hepatocellular and adrenal failure and
biochemical disturbances (death usually occurs within 1 - 4 days);
(b) less overwhelming poisoning with slower onset of organ failure and death
from pulmonary oedema, mediastinitis, and complications of therapy
(c) late pulmonary fibrosis (death ensuing 4 days to several weeks later).

Soon after ingestion, there is

- oropharyngeal pain and swelling, followed within a few days by

- exudation,
- ulceration, and
- mucosal sloughing, sometimes with
- pseudomembrane formation, which on occasion leads to
- total sloughing of the oropharynx and oesophagus.
In severe poisoning,
-pulmonary oedema rapidly ensues with clinical and functional
deterioration until death.
Less intense, but ultimately fatal, poisoning causes progressive
- pulmonary fibrosis over days or several weeks, with gradually
increasing
- dyspnoea and
- hypoxaemic pulmonary failure.
- Pulmonary oedema may occur from fluid overload in oliguric
patients.
- Mediasteinitis and
- pneumothorax are occasionally seen
Investigation
- Pulmonary function tests reflect the underlying pathology, with
- hypoxaemia, reduction in lung volume
- high alveolar-arterial gradient
- impaired gas transfer
- Chest radiographs may show
- bilateral pulmonary oedema, coalescing consolidations
- pulmonary fibrosis (later)
Respiratory
system

Gross autopsy findings in lungs:- Lungs do not collapse properly and the pleural cavity
contains a small amount of fluid.
- In cases of lung fibrosis, the lungs are - heavy/firm/ dark
purple/ rubbery
-Consolidation and decreased aeration are found
predominantly at bases.
- Emphysema and atelectasis are often found.
Histological studies: following necropsy show
- pulmonary oedema, haemorrhages
- atelectasis due to pulmonary infiltrates,
- loss of alveolar epithelial cells and, at a later
stage,
- interstitial and intra-alveolar fibrosis
During the first 7 days of paraquat poisoning in man,
- loss of alveolar epithelial cells has been seen with
alterations
- detachment of, the type I and II cells,
- proliferation of fibroblasts and polymorphous cells,

Renal
system

Gastrointes
tinal
system,
the liver,
and the
pancreas

Cardiovasc
ular system

Central

- loss of surfactant secretion, and

- thickening of the alveolar septa by interstitial
fibrosis
later findings (2 - 3 weeks) involved
- pulmonary fibrosis and endothelial abnormalities
- Capillary permeability seemed to be enhanced either by
- vesicles forming transendothelial channels or by
- disruption of endothelial cells.
In severely poisoned patients.
- Acute oliguric renal failure is common
In less severe manifestations include impaired renal
function, which may disappear before the pulmonary
fibrosis progresses.
Other manifestations include
- proteinuria, with hyaline casts, white and red blood cells.
-Tubular damage is reflected in glycosuria, aminoaciduria,
and excessive leaking of phosphorus, sodium, and uric acid
Kidney in Autopsy
- Soft, pale, swollen kidneys with extensive tubular
necrosis, compatible with toxic injury,
- Sometimes necrosis of the proximal tubules is found
together with
- extreme dilatation of the distal tubules of the kidney
The initial symptoms after oral ingestion of paraquat are:- N/V
- upper abdominal pain
- diarrhoea
- Perforation of the oesophagus (uncommon).
The ingestion of large doses of paraquat has resulted in
- severe liver damage with
- progressive metabolic acidosis.
Liver:- - Fatty degeneration of periportal hepatocytes and
- sporadic cellular necrosis in the central region of
the liver lobules
- Cholestasis and portal inflammation may occur
- Oedematous degeneration or
- necrosis of intra-hepatic and extra- hepatic bile
ducts, gall bladder
Pancreas - stasis of the pancreatic duct, with
- increased serum amylase levels after (In severe
paraquat poisoning.)
toxic myocarditis, fibrinoidal necrosis of the small arteries
in the pancreas, kidney, and liver on days 3 - 6 following
ingestion.
The ingestion of very high doses of paraquat provoked

nervous
system

o
o
o

Adrenal
glands

- anxiety,
- convulsions,
- ataxia, and
- semi-consciousness
Autopsy findings:- Haemorrhagic leukoencephalopathy was present
throughout the CNS, involving almost exclusively the white
matter.
- Focal haemorrhage and demyelinization were present at
various stages together with haemorrhagic meningitis.
Adrenal cortical necrosis may contribute to death in severe
paraquat poisoning and the severity of the damage
appears to be dose-related

Organophosphorus Insecticides
Eg: Parathion, Malathion
Toxic effects results in accumulation of acetylcholine in nerve tissus and
effector organs (inhibition of acetylcholinesterase in the nervous system)
Clinical features:
symptoms developed within
lacrimation
12 hours
sweating, nausea, vomiting
chest tightness
& diarrhoea
(bronchoconstriction &
pupils constriction
increased bronchial
fatigue, weakness & cramps
secretions)
Death due to acute
increased salivation
respiratory failure

Treatment:
maintain patients airway
intravenous atropine
control convulsions
antidote = pralidoxime

Drugs of abuse
opiate- eg. Morphine, codeine
opioids- eg. Heroin, pethidine, methadone
narcotic analgesics
cannabis and cannabinoids eg. Tetrahydrocannabinol
cocaine eg. Crack cocaine (freebase)
hallucinogens- psychedelic or psychothropic drugs eg. LSD (lysergic acid
diethylamide), amphetamines eg. MDA, MDMA (ecstacy=E=adam), PCP
(phencyclidine, angel dust)
alcohol, cobalt, etc

Common drugs of
Routes of administration;abuse
orally
Heroin & morphine
chewing eg. Cannabis leaves
Cannabis
nasal inhalation/ snorting eg. Cocaine
Amphetamine type
intravenous eg. Heroin mainlining
stimulants
smoking (freebasing) eg. Marijuana, cocaine

Morphine & heroin

by intra-venous injection (rapid onset of action)
heroin > potent than heroin
rapidly metabolised by the liver
metabolites excreted in the urine
Heroin monoacetyl morphine (rapid conversion, so no heroin in the urine)
Therefore, morphine in the urine = either morphine or heroin abuser.
Signs & symptoms : nausea, vomiting, euphoria, analgesia, sedation &
respiratory depression.
Pinpoint pupils
acute overdose can cause death

Cannabis (marijuana , ganja)

active agent = tetrahydrocannabinol
hand-rolledcigarette
onset of drug action within few minutes
Effects:- relaxation, sense of well-being, alteration in perception and
impaired memory.
Severe intoxication:- slurred speech, loss of coordination, hallucinations,
delusions and paranoia.
Signs:- tachycardia, impotence, fine tremor, constipation, nystagmus,
bronchial irritation and hypothermia.

Amphetamine type stimulants (ecstacy)

taken orally
Raised blood pressure, low heart rate, relaxation of bronchial muscle.
fight or flightreaction:- increase blood sugar, blood flow to muscles,
respiratory & heart rate, and pupillary dilatation
Increased alertnwss, euphoria, wakefulness, decrease of apetite, increased
motor & speech activity.
Prolonged use:- tremor, restlessness, insomnia & agitation.

Severe poisoning:- intense hypertension, tachycardia, arthythmias & fever.

Convulsions may occur followed by circulatory collapse, coma & death

Pathological effects of drug abuse

Swallowed drug to conceal: known as stuffers/ loaders/ swallowers
Vegetations on heart valves
Talc/ glass + mainlining: Talc granulomatosis respiratory impairment
Injection sites of IVDU -Mainlining, causes hardened veins or
thrombophlebitis
Injection of heroin into s/c - skin popping
Immunocompromised IVDU: PTB, acute meningitis
Opportunistic infections of lung e.g; Pneumocystic carinii, Candida
albicans, Cryptococcal neoformans, fungal infx
Cocaine - intracerebral bleed, LVH decompensated HF

Cause of death in drug abuse case

Acute poisoning
APO d/t poisoning
Alcohol/ drug intoxication
Drug overdose
Drug related deaths
Retroviral infection, AIDS, HIV, septicaemia, deaths from opportunistic infx

Other poison rare (Ipoh poison)

Blowpipe, dart, ipoh tree, homicidal

The Doctors Role In Poisoning

The recognition or suspicion of the fact of poisoning
The early diagnosis, where possible, of the nature of the poison
Emergency primary treatment and admission to hospital where necessary
The identification and retention of residual poison in the house, for
transmission to the hospital to confirm the nature of the poison
Where death has occurred, full cooperation with the pathologist in
providing details of any illness, psychiatric condition and drugs recently
prescribed.

Diagnosis:
should be considered in patients with coma, convulsions, acute hepatic,
renal and bone marrow failure.
Ask patient, relatives and friends about possible poisons.
Specimens of blood, urine, vomitus and gastric aspirate should be sent
immediately for analysis.

Treatment:
Gastric lavage (avoid following ingestion of kerosene)
Minimise absorption (activated charcoal)
Enhance renal excretion (forced diuresis with saline + IV furosemide)
Supportive therapy:
maintenance of ventilation when CNS is depressed
anticonvulsants in patients with convulsions

o
o
o
o
o

cerebral oedema treated with IV corticosteroid and/or IV

hypertonic mannitol
patients should be evaluated and treated for the effects of
poisoning e.g. hypovolemia, hypotension, cardiac arrhythmias,
pulmonary oedema, hypoxia, acute renal failure,acute hepatic
failure and disturbances of fluid and electrolytes.

Postmortem Detection of Toxic Substances

History
External Examination
Internal Examination
Collection of appropriate specimens
o blood, urine, stomach contents, liver tissue, lung tissue, muscle etc.
Analysis (P.J. Chemistry Lab)

Collection of specimen (Autopsy cases)

Blood, urine, bile & vitreous should be collected if available
use new needle & syringe
use glass containers, not plastic
blood from femoral vessels (subclavian vessels, root of aorta, pulmonary
artery or superior vena cava)
seal & label specimens
tissue :- right lobe of the liver or muscle
Request form
maintain chain of custody