TOXICOLOGY

It is the study of substances that are toxic to the

body.
Absorption of toxins in the GIT is by diffusion
this process requires that the substance cross
cellular barriers.
Toxins that are not absorbed from the GIT do not
produce systemic effects but may produce local
effects diarrhea, bleeding and malabsorption of
nutrients.
 In cases of drug overdose, CBC, serum
electrolytes, BUN, glucose, U/A and
blood gas must be determined.
Common substances causing toxicity
alcohol, acetaminophen, salicylate,
abuse substances and carbon
monoxide.
Routes of exposure ingestion,
inhalation, and transdermal absorption
 TERMINOLOGIES
ACUTE TOXICITY
- single, short term exposure to a substance
CHRONIC TOXICITY
- repeated exposure for extended period of time.
TD50
- the dose that would be predicted to produce a toxic
response in 50% of the population.
LD50
- the dose that would predict death in 50% of the population
ED50
- the dose that would be predicted to be effective or have a
therapeutic benefit in 50% of the population.
 ALCOHOLS
The are commonly CNS depressants
It causes disorientation, euphoria, confusion and
may progress to unconsciousness, paralysis and
even death.
Symptoms of alcohol intoxication begin when the
concentration is > 0.05% w/v (>50mg/dL blood
alcohol)
ETHYL ALCOHOL (ETHANOL)
Also known as the grain alcohol
Most common drug abused
Most ethanol is converted to acetic acid
Increased in GGT,AST,AST/ALT ratio (>2.0), HDL and MCV.
Ethanol abuse causes acidosis through accumulation of
ketones and lactate and also through direct generation of
hydrogen ions as alcohol is oxidized, it also adds to
osmolality of blood.
Serum, Plasma and Whole blood are acceptable specimens
(the venipuncture site should be cleaned with alcohol free
antiseptic benzalkonium chloride)
The specimen must be capped all the time to avoid
evaporation of alcohol.
 The body eliminates alcohol at a range of
0.015%/hr.
It is also found in a variety of colognes,
perfumes and after shaves, some rubbing
alcohols, food flavourings and pharmaceutical
preparation.
In addition to ethanol content, most beverages
contain congeners (small amount of ethers,
aldehydes, ketones and essential oils)
Basically it is a CNS depressant not a stimulant,
acting similarly to that of general anaesthetics.
 Major metabolic pathway: conversion to acetaldehyde by
alcohol dehydrogenase (AD)
Methods for testing: enzymatic (AD) GLC and osmometry.
Detection limit:
12 hours
Fatal dose:
300 400 mL of pure alcohol consumed in less than one
hour
Toxic blood levels:
250 400mg/dL
Diagnosis:
Based on the history of ingestion, characteristics smell of fresh
alcohol, of fetid color of acetaldehyde and the presence of
nystagmus, ataxia and altered mental status.
 SPECIFIC LEVELS: BLOOD ALCOHOL VALUES
LESS THAN 0.05% - not under the influence of
drug.
0.05 0.10% - evidence with outward physical
symptoms
0.10 0.25% - the subject is under the
influence of alcohol
0.25 0.40% - the subject is markedly
intoxicated
0.40 above comatose levels which may lead
to death
TREATMENT:
1. Acute intoxication: Treatment is supportive
Airway
Glucose , thiamine.
Patient usually recover 4 6 hours.
2. Alcohol withdrawal: Benzodiazepines
(diazepam, 2 10mg)
3. Decontamination: Gastric lavage is usually
not indicated because alcohol is rapidly
absorbed.
 METHYL ALCOHOL (METHANOL, WOOD
ALCOHOL)
Commonly used solvent and a contaminant of
homemade liquors.
It is common ingredient in many solvents,
windshield washing solutions, duplicating fluids,
paints and varnishes and paint removers.
Used as a substitute by alcoholics
Fatal dose: 60 250 mL
Converted first to formaldehyde to formic acid in
the liver. (blindness)
 ISOPROPANOL (RUBBING ALCOHOL)
Used as a solvent, antiseptic and disinfectant
70% rubbing alcohol
Fatal dose: 250 mL

ETHYLENE GLYCOL (1,2 ETHANODIOL)

It is a common constituent of hydraulic fluids and
antifreeze.
It is converted to oxalic acid and glycolic acid.
Production of final products leads to deposition of
calcium oxalate crystals in renal tubules
Fatal dose : 100 grams
SEATWORK
CARBON MONOXIDE (CO)
It is a colorless, odorless, tasteless gas; very toxic
substance.
It is produced by incomplete combustion of carbon
containing substances like gasoline engines,
improperly ventilated furnaces and wood or plastic
fires.
Toxic effects are manifested by binding with heme
proteins (cytochromes, myoglobin and
hemoglobin.)
It has higher affinity for hemoglobin than does
oxygen impairs oxygen transport by binding to
hemoglobin producing carboxyhemoglobin
 It inhibits cellular respiration and
electron transport.
Net effect: tissue hypoxia
Toxic levels: 20% CO
Indicator of toxicity: cherry red color
of the face
Sample for testing: EDTA whole blood
Method for testing: co oximetry
(carboxyhemoglobin measurement)
CYANIDE
Super toxic
Exist as a gas, solid or liquid
Use in many industrial processes
Component of some insecticide and rodenticide;
common suicide agent
Produced as a pyrolysis (decomposition of organic
material without the participation of oxygen)
Expresses toxicity by binding heme iron.
It inhibits cellular respiration, electron transport and
ATP formation.
It has characteristics odor of bitter almonds
Toxic levels: >2 g/mL
 PESTICIDES Organophosphates and
Carbamates
Organophosphates are synthetic derivatives of
carbamic acid
It inhibits the enzyme acetyl cholinesterase (AchE)
S/S: parasympathetic manifestation such as SLUD
Salivation, Lacrimation, Urination and Defecation.,
papillary constriction, bradycardia and
bronchoconstriction.
Treatment: respiratory support, gastric lavage or
emesis.
METALS
ARSENIC
Component of ant poison, rodenticides, paints
and metal alloys.
It is a common homicide or suicide agent;
common agent of heavy metal poisoning.
It inhibits sulfhydryl enzymes throughout the
body
It expresses the toxicity by high affinity binding to
the thiol groups in proteins.
Exist in both naturally occuring and manmade
substances
 It has a characteristics of odor of garlic
and metallic taste
The used of hair and nails (mees lines) as
specimens are important in the evaluation
of long term (chronic) exposure ion
emission spectroscopy.
Blood and urine specimens for short
term (acute exposure)
Acute fatal dose: 120mg
Methods for testing: Reinsch test, AAS
 CADMIUM
It is utilized in electroplating and galvanizing
It is a significant environmental pollutant
pigment in paints and plastics.
Poisoning can result from ingestion of acidic
foods stored or prepared in metal
containers made up of cadmium.
It may also accumulate in renal tubules
causing tubular damage.
Toxic renal indicator: (+) GGT in urine
sample
LEAD
It is a component of household paints and a
potent enzyme inhibitor
Exposure to this metal results to encephalopathy,
birth defects and compromised immunity.
Low level exposure may cause behavioral changes
hyperactivity and attentional deficit disorder,
and also affect intelligence qoutient scores.
Vitamin D and heme synthesis pathway are
affected lead blocks delta aminolevulinic acid
(ALA) synthetace, producing anemia.
 It has a characteristics wrist drop or foot
drop manifestation.
EDTA and dimercaptosuccinic acid (DMA) are
used for treatment as therapeutic chelaters
to remove lead from soft tissues and bone.
Toxicity dose: >0.5 mg/day
Fatal dose: 0.5g
CDC cutoff for normal lead in children: <
10g/dL
Toxic blood levels: > 70 g/dL (definitive lead
poisoning)
METHODS:
SAMPLES: whole blood, urine and hair
Whole blood is the sample of choice for
quantitative testing and it will produce the
greatest sensitivity (long time exposure)
Urine is used for the assessment of recent lead
exposure.
Testing for the diagnosis of lead poisoning shpuld
include analysis of morning urine for delta ALA.
Indicator of Lead Toxicity: increase urinary ALA,
Free RBC porphyrin and presence of basophilic
stipplings in RBC.
 TESTS:
Graphic furnace AAS (children), inductively
coupled emission spectrophotometry
(ICPES, anodic stripping voltammetry)
Zinc protoporphyrin or free RBC
protoporphyrin test is useful to assess blood
concentration of lead.
 MERCURY
Binds with proteins and also an enzyme inhibitor.
It has the ability to amalgamate mix or merge
with other substances.
Exist in three forms: elemental (liquid), inorganic
salts (solid) and components of organic
compounds.
Small drops of mercury on benchtops and floors
can poison the environment in a poorly ventilated
room.
The presence of this substance in blood may
result to loss of glomerular integrity.
 if inhaled or absorbed through the skin it
can pass through the blood brain
barrier, and can accumulate in the CNS.
Samples for testing: whole blood (organic
mercury) and urine (inorganic mercury)
Methods for testing: Reinsch test
TOXICOLOGY OF THERAPEUTIC DRUGS
SALICYLATES
ASPIRIN (acetylsalicylic acid) commonly
used as analgesic, antipyretic, anti
inflammatory drug, antiplatelet/anticlotting
Decreases thromboxane and prostaglandins
formation
Direct stimulators of respiratory center
Inhibits the Krebs cycle.
TOXICOLOGY OF THERAPEUTIC DRUGS
ACETAMINOPHEN
Paracetamol causes spontaneous
abortion , it can destroy liver
Solely or combination with other
compounds
Use as analgesic drug.