Toxicology is the study of the harmful effects of chemicals on living organisms, with toxicologists studying these effects and assessing the probability of their occurrence. The document outlines the key aspects of toxicology including what it entails, common toxic agents, how toxicity is classified and measured, diagnostic evaluation of potential poisoning, and general management approaches for poisoning patients. Toxicology plays an important role in various fields including public health, forensics, occupational safety and environmental protection.
2. What is ď The science of toxicology, or the
science of poisons, is the study of
toxicology? the harmful effects of chemicals on
living organisms.
⢠Is the science of poisons,
including not only their physical
and chemical effects but also
ď Scientists who study these harmful
their detection and antidotes effects and assess the probability of
their occurrence are called
⢠The branch of pharmacology toxicologists.
that deals with the nature and
effects and treatments of ď Toxicology encompasses the study of
poisons (Xenobiotics) the adverse effects of chemicals on
living organisms.
⢠Is the study of the adverse
effects of chemicals on living ď Toxicology assesses the probability
organisms. of hazards caused by such effects.
â˘Itis the study of symptoms, ď Toxicology estimates the results of
mechanisms, treatments and
these effects on animal and human
detection of poisoning,
populations.
especially the poisoning of
people.
Toxicity â is the ability of the substance to produce injury upon
reaching a susceptible site in/on the body
3. ContâŚ
⢠Toxicological studies consider ⢠The important science of
the cause, circumstances, toxicology has direct
effects and limits of safety of relevance to human health,
unintended harmful effects of the environment and major
food, food additives, drugs, sectors of the economy.
household and industrial
products or wastes. ⢠The scientific community,
governments, industry and
⢠Toxicological studies deal with the public all require
adverse effects ranging from information on the effects of
acute to long-term. potentially hazardous
substances to balance the
benefits which society
receives against the hazards
that may occur from their use
and misuse.
The term âtoxicityâ is used to describe the nature of adverse
effects produced and the conditions necessary for their
production.
4. ďMECHANISTIC ďDESCRIPTIVE
⌠Elucidate the cellular ⌠Uses results from
and biochemical animal experiments
effects of toxins. to predict the level of
⌠Provides basis of exposure harmful to
therapy designs and humans (risk
develop tests for assessment)
assessment
Four Major Disciplines of
Toxicology
5. ďFORENSIC ďCLINICAL
⌠Concerned with ⌠Study the
medicolegal interrelationships
consequences of toxin between toxin
exposures exposure and disease
⌠To establish and states
validate analytical ⌠Both diagnostics and
performance of interventions
methods used as
evidence for legal
purposes
Four Major Disciplines of
Toxicology
6. Sub-disciplines of Toxicology
â Helps to establish cause
⢠Economic toxicology
and effect relationships
â Concerned with
between exposure to a
chemicals used in drugs,
drug or chemical and the
food additives,
toxic or lethal effects
pesticides and cosmetics
that result.
⢠Forensic toxicology ⢠Clinical toxicology
â Involves the medical and
â Is concerned with
legal aspects of
diseases and illnesses
poisonous materials
associated with short
when death or severe
term or long term
injury is the result of
exposure to toxic
their use
chemicals.
The term âtoxicantâ refers to toxic substances that are
produced by or are a by product of human-made activities.
7. ContâŚ
ď Environmental â Deals with toxic
substances that enter the
toxicology waterways, such as lakes,
⌠Evaluates the synergistic streams, rivers and
effects of chemicals in oceans.
the environment
⌠Studies chemicals that
are contaminants of
Fact: Most common
food, water, soil, or the problems include
air. water-borne bacteria
and viruses, waste
heat from electrical
plants, radioactive
wastes, sewage, and
industrial pollution.
The term âtoxinâ refers to toxic substances that are produced
naturally.
8. ďIndustrial Fact: Occupational
(Occupational) diseases caused by
toxicology industrial chemicals
⌠Evaluates the effects account for an
of pollutants in the estimated 50,000 to
working environment
70,000 deaths and
⌠Protects workers from
350,000 new cases
toxic substances and
makes their work of illness each year
environment safe. in the United
States.
ContâŚ
9. ⢠Gathers data about ⢠Determines whether
poisons the substance is
hazardous or not
⢠Identifies the substance
causing poisoning ⢠Provides antidote for
every causative agent
⢠Quantifies the amount
of poisons ⢠Gives advice about
treatment
⢠Interprets laboratory
results ⢠Monitors certain
chemical substance in
⢠Controls the marketing patients
of the poisons
General functions of a toxicologist
10. ⢠Moses Maimonides ⢠A famous Jewish
(1135-1204) Philosopher,
Maimonides was born
in Spain and he was
educated at the
University of Fes.
⢠Among other things,
Maimonides wrote the
famous Treatise on
Poisons and Their
Antidotes.
Some individuals who contributed
to the field of toxicology
11. ďParacelsus ďFamous for his
(1493-1541) words "the dose
makes the poisonâ
ďâAll substances are
poisons;
there is none which
is not a poison.
The right dose
differentiates a
poison from a
remedy.â
ContâŚ
12. ⢠Francois Magendie ⢠Born in France,
(1783-1855) Magendie researched
the different motor
functions of the body
in relation to the
spine, as well as
nerves within it.
⢠In addition, he
researched the
effects of morphine,
quinine, strychnine,
and a multitude of
alkaloids.
⢠Noted as the father of
experimental
Cont⌠pharmacology.
13. ⢠Mathieu Joseph
Bonaventure
Orfila /Mateu Josep
Bonaventura Orfila
i Rotger) (April 24,
1787 â March 12,
1853) was a Spanish-
born French
toxicologist and
chemist, the founder
of the science of
toxicology.
ContâŚ
14. ďEmilFischer ďEmil Fischer
1852-1919 synthesized caffeine
and received the
nobel prize in
chemistry in 1902.
ContâŚ
15. A. Bases on its analysis
B. Based on the organ or system
considered the target site of the effect of
the chemical
C. Mechanism of toxicity
D. Manner of exposure
4 bases in in classifying poisons
16. ďHeavy Metals
ďSolvents and Vapors
ďRadiation and Radioactive Materials
ďDioxin/Furans
ďPesticides
ďPlant Toxins
ďAnimal Toxins
Classification of Toxic Agents
17. Characteristics of exposure
Measurement of toxicity
Types of exposure
related to:
ď Characteristics and 1. Acute exposure â
condition of exposure an exposure in
which the dose is
ď Route of delivered in a single
administration event and the
absorption process
ď Time and frequency is rapid
of exposure
1. Chronic exposure â
ď Dose delivered the dose is
delivered at some
ď Physical
frequency over a
and chemical period of time
form of the substance
18. A. Pulmonary - administration via the
lungs; the duration of exposure would
ordinarily long (inhalation of toxic gases)
B. GIT or oral â administration is through
the mouth in which the result is delayed
due to the absorption process and
distribution of the toxic substances to its
active sites will have the bearing on the
effects observed
Routes of Administration
20. Spectrum of Types of effects based
toxic effects on locus of action
Acute effect 1. Local effects
⢠Effects that occur or â Effects that occur at
the site of the first
develop rapidly after a contact between the
single administration biologic system and
the toxicant
Chronic effect
⢠Those that are 2. Systemic effects
manifested after the â Are effects that
require absorption
elapse of some time and distribution of
the toxicant to a site
distant from its entry
point effects are
produced (frequently
involved is the CNS)
21. Toxicity ratings Commonly used Probable human
terms lethal dose LD
6 Super-toxic < 5mg/Kg (a taste
<7gtts)
5 Extremely toxic 5-50mg/Kg (bet 7gtts
â 1tsp)
4 Very toxic 50-500mg/Kg (bet
1tsp â 1oz)
3 Moderately toxic 0.5-5g/Kg (bet 1oz â
1pint)
2 Slightly toxic 5-15g/Kg (bet 1 pint
â 1 quart)
1 Practically non-toxic 15g/kg (>1 quart)
Classification of toxicants based
on their relative toxicities
22. Cases of poisoning Diagnostic workup of a
generally fall into 3 patient who may be a
categories victim of poisoning
1. Exposure to a known 1. Complete history
poison
2. Complete physical
2. Exposure to an examination
unknown substance
which may be a 3. Appropriate
poison
laboratory
examination
3. Disease of
undetermined
etiology in which
poisoning must be
considered as part of
the differential
diagnosis
23. ⢠Poisoning
â Defined as an overdose of drugs, medicaments,
chemicals and biological substances
⢠Self-Poisoning/Parasuicide
â Used to refer to the deliberate ingestion of more than
the therapeutic dose of a drug or a substance not
intended for consumption, usually by an adult in a
moment of distress; dose who die are classed as suicides
rather then parasuicides regardless of whether or not
this was the intended outcome
⢠Accidental Poisoning
â Non-intentional ingestion overdose or exposure to drugs,
medicaments or poisonous substances
General measures in the
management of poisoning
24. I. Emergency V. Administration of
stabilization antidotes
II. Clinical Evaluation VI. Supportive
III. Elimination of the therapy and
poison observation
IV. Excretion of VII. Disposition
absorbed
substances
The general approach to the
poisoning patient may be divided
into:
25. ďABCDE
⌠Airway obstruction
⌠Breathing difficulties
⌠Circulatory inadequacies
⌠Drug-induced CNS depression
⌠Electrolyte or metabolic abnormalities
The greatest contributor to death from drug
overdose is loss of airway protective reflexes
with subsequent airway protection by flaccid
tongue, pulmonary aspiration of gastric
contents or respiratory arrest.
Emergency Stabilization
26. SNIFFING POSITION
⌠The neck is flexed forward and the head
extended
⌠Should not be used if there is any suspicion of
neck injury
Techniques to clear airway
27. CHIN-LIFT
1. The fingers of one hand are placed
under the mandible, which is gently
lifted upward to bring the chin
anterior.
2. The thumb of the same hand
depresses the lower lip to open the
mouth.
3. The thumb may also be laced
behind the lower incisors and,
simultaneously, the chin is gently
lifted. ContâŚ
28. JAW THRUST
⌠Technique to open the
airway by placing the
fingers behind the
angle of the jaw and
bringing the jaw
forward; used when a
patient may have a
cervical spine injury
⌠To create forward
movement of the
tongue without flexing
or extending the neck
ContâŚ
29. HEAD-DOWN LEFT SIDED POSITION
⌠Allows the tongue to fall forward and secretions
or vomitus to drain out of the mouth
ContâŚ
30. Intubation Contraindications
ď OROTRACHEAL 1. Severe airway trauma or
Indications obstruction that does not
1. Inadequate oxygenation permit safe passage of an
(decreased arterial PO2, etc.) endotracheal tube.
that is not corrected by Emergency
supplemental oxygen supplied cricothyrotomy is
by mask or nasal prongs. indicated in such cases.
2. Inadequate ventilation 2. Cervical spine injury, in
(increased arterial PCO2). which the need for
3. Need to control and remove complete immobilization
pulmonary secretions (bronchial of the cervical spine
toilet). makes endotracheal
intubation difficult.
4. Need to provide airway
protection in an obtunded
patient or a patient with a
depressed gag reflex (for
example during a general
anesthesia).
31. ContâŚ
Preparing the The inability to ventilate a
Procedure patient is bad. Also a
mnemonic SALT source of O2 with a
Suction. This is extremely delivery mechanism
important. Often (ambu-bag and mask)
patients will have must be available.
material in the pharynx, Laryngoscope. This
making visualization of lighted tool is vital to
the vocal cords difficult. placing an endotracheal
Pulmonary Aspiration tube.
should be avoided. Tube. Endotracheal tubes
Airway. the oral airway is come in many sizes. In
a device that lifts the the average adult a size
tongue off the posterior 7.0 or 8.0 oral
pharynx, often making it endotracheal tube will
easier to mask ventilate work just fine.
a patient.
32. Advantages Disadvantages
1.Performed under 1.Frequently requires
direct vision neuromuscular
2.Insignificant risk of paralysis
bleeding 2.Requires neck
3.Patient need not be manipulation
breathing
spontaneously
4.Higher success rate
Cont⌠Orotracheal Intubation
34. Advantages Disadvantages
⌠May be performed ⌠Perforation of the
in a conscious nasal mucosa with
patient without epistaxis
requiring ⌠Stimulation of
neuromuscular vomiting in an
paralysis obtunded patient
⌠Better tolerated ⌠Patient must be
once placed breathing
spontaneously
⌠Difficult in infants
anatomically because
of anterior epiglottis
ContâŚ
35. B. Physical
A. History examination
1. Time of exposure HYPOTHERMIA
2. Mode of exposure ⌠A condition in which the
3. Intake of other patient has a rectal
substances temperature of < 30oC
4. Circumstances prior ⌠May be due to overdose
of :
to poisoning ď Alcohol
5. Current medication ď CO
6. Past medical history ď Opioids
7. Any home remedy ď Sedative-hypnotics
taken ď Barbiturates
Clinical Evaluation
36. HYPERTHERMIA HYPOGLYCEMIA
⌠A condition when the ⌠An abnormally
rectal temperature is diminished content of
> 40oC glucose in the blood
⌠May be due to ⌠A common finding in
overdose of: alcohol intoxication
ď Antihistamines and salicylates
ď Amphetamines toxicity
ď Cocaine
ď Anticholinergic HYPOCALCEMIA â reduction of blood
ď Isoniazid calcium below normal; commonly seen in
dancing firecrackers, jatropa seed
ingestion, complications of severe animal
bites and stings
Cont⌠Physical Examination
37. 1. Evaluate general
status of patient
ď Tachycardia â CO, HCN, 2. Examine patient skin
organophosphates, ď Needle tracks, bruises and
ethanol lacerations
ď Bradycardia â digitalis ď Cutaneous bullae â
ď Hypertension â cocaine, Barbiturates and CO poisoning
caffeine, ď Diaphoresis -
amphetamines, nicotine organophosphates, salicylates
ď Hypotension â and amphetamine toxicity
ď Jaundice â
antidepressant, acetaminophen/hepatotoxic
heroine, opiates, agents
sedative-hypnotics ď Dry skin and hyperpyrexia -
atropine and anticholinergic
agents
ď Flushing â alcohol, CN and CO
Physical Examination
39. 5. Listen to patientâs heart
6. Check the abdomen
7. Do a complete neurologic examination
⌠Using the Glasgow Coma Scale
⌠The scale comprises three tests: eye, verbal and motor responses. The
three values separately as well as their sum are considered. The lowest
possible GCS (the sum) is 3 (deep coma or death), while the highest is
15 (fully awake person).
ContâŚ
40. Glasgow Coma Scale
1 2 3 4 5 6
Opens eyes in Opens eyes
Does not Opens eyes
Eyes response to painful in response N/A N/A
open eyes spontaneously
stimuli to voice
Utters Oriented,
Makes no Incomprehensible Confused,
Verbal inappropriate converses N/A
sounds sounds disoriented
words normally
Abnormal
Flexion / Localizes Obeys
Makes no Extension to painful flexion to
Motor Withdrawal to painful Comman
movements stimuli painful
painful stimuli stimuli ds
stimuli
41. Elimination of Poisons
A. External decontamination
⌠Discard patientâs clothing
⌠Bathe or shower the patient
⌠Copious irrigation with water in eye
contamination
A. Empty the stomach â emesis and gastric
lavage
B. Limit Gastrointestinal Absorption â activated
charcoal lavage
C. Dialysis and Hemoperfusion
D. Whole bowel irrigation
Differences in response to toxicant in a population
due to:
Genetics; Gender; Age; Nutritional Status; Health
Condition; Previous or concurrent exposure to other
substances
42. Absorption Distribution
ď Intravenous â 100% ď Translocate throughout
bioavailable (no limiting the body
factors)
ď Inhalation â must ď Blood carries to and
penetrate alveolar sacs of from its sites of action
lungs, then into the ď Stored/deposited
capillary bed
ď Ingestion â requires
(adipose tissues, bones
absorption through the â lead and fluoride
GIT ď Organs
ď Dermal/topical â requires biotransformation
absorption through the ď Elimination
skin
EXCRETION: Absorption,
Distribution and Metabolism
43. ContâŚ
Metabolism
ď Parent compound are Excretion
modified by the ď Urinary â water
organism via the soluble products are
enzymes filtered out of the
ď Primary objective is to blood
make chemical agents ď Exhalation â volatile
more soluble to water compounds
for easier excretion ď Biliary excretion via
fecal excretion â liver
ď biotransformed ď
bileď small intestine
Biotransformation ď feces
occur: liver; lungs;
kidneys and intestines
45. CARBON MONOXIDE
- colorless, tasteless, odorless and non-irritating gas
- a by-product of incomplete combustion
- 0.1ppm is the average concentration of CO in the atmosphere
- in heavy traffic the concentration may exceed 100ppm
- the brain and heart are the organs mostly affected
Sources Mechanism of toxicity
ď Smoke inhalation in fires ď CO binds to
ď Automobile exhaust
hemoglobin with an
fumes
ď Faulty or poorly
affinity 210 â 250
ventilated charcoal. times that of O2 ď
Kerosene and gas stoves reduced
ď Cigarette smoke oxyhemoglobin
ď Methylene chloride â a
saturation and
-Inhibits cytochrome oxidase,
solvent in paint further disrupting cellularO -
decreased blood function
removers in metabolized 2
- known to bind to myoglobin ď
to CO carrying capacity
impaired myocardial contractility
46. Net effects ď Once CO is discontinued,
1. Tissue hypoxia dissociation of the
2. Anaerobic hemoglobin-CO complex
metabolism occurs and CO is excreted
through the lungs
3. Lactic acidosis
ď At room air the CO half-
-A normal non- life is 4 to 6 hours
smoking adult has ď Half-life decreases to 40
COHb level of < 1% to 80 minutes when
saturation breathing 100% O2
- Smokers will ď Half-life is 15 to 30 mins
exhibit 5 â 10%
with hyperbaric O2 therapy
saturation
depending on the
habit
47. 1. Psychomotor impairment
2. Headache and tightness in the temporal
area
3. Confusion and loss of visual acuity
4. Tachycardia, tachypnea, syncope and
coma
5. Deep coma, convulsion, shock and
respiratory failure
Principal Signs of CO intoxication:
HYPOXIA
48. Estimated CO COHb % Symptoms
concentration
Less than 35ppm 5 None, or mild
(cigarette smoking headache
0.005% (50ppm) 10 Slight headache,
dyspnea on vigorous
exertion
0.01% (100ppm) 20 Throbbing headache,
dyspnea with
moderate exertion
0.02% (200ppm) 30 Severe headache,
irritability, fatigue,
dimness of vision
0.03%-0.05% (300- 40-50 Headache,
500ppm) tachycardia,
confusion, lethargy,
collapse
0.08%-0.12% (800- 60-70 Coma, convulsions
1200ppm)
0.19% (1900ppm) 80 Rapidly fatal
49. Toxic dose Diagnosis
ď Permissible exposure ď History of exposure
limit (PEL) is 35ppm as (locked garage
an 8-hour time weighted
ď Cherry red skin
average
ď Immediate dangerous to coloration or bright
life or death (IDLH) is red venous blood
1500ppm or 0.15% ď Measurement of COHb
ď Several exposure to
1000ppm or 0.1% may
result in 50% saturation
of COHb and fatal
poisoning
50. Treatment Decontamination
ď Emergency ď Remove patient from
and
supportive measures exposure and give
ď Specific drug and supplemental O2
ď Rescuers should wear
antidote: Administer
OXYGEN in the self-contained
highest possible breathing apparatus
concentration
Enhance Elimination: HYPERBARIC OXYGEN
which provides 100% oxygen under 2-3 atm
pressure
51. HYDROGEN CYANIDE
- A colorles, very volatile gas or liquid and resembling an
odor that of bitter almonds
- Lighter than air ď rises and diffuses rapidly
- By-product of burnt plastics, wood and many natural and
synthetic materials
Synonyms:
ď CYCLON ď CN binds avidly to iron
ď Formonitrile in the ferric forming
ď Hydridonitridocarbon cyanoferric complex ď
ď Hydrocyanic acid inactivation of iron
(prussic) containing enzymes
52. Mechanism of toxicity Clinical Presentation
ď CN produces tissue and ď Initially (tachypnea)
cellular hypoxia by ď Respiratory
reversibly binding into depression and
cytochrome A and by cyanosis
inhibiting re-oxidation ď Hypotension
ď Inhibits electron ď Convulsion
transport; prevent ď Coma
cellular respiration and ď Death will occur in
decrease ATP production minutes at significant
ď Produce severe amount because it is a
metabolic acidosis fast acting poison
ď Cyanohemoglobin which
cannot transport oxygen
53. Treatment
1. Amyl nitrite (inhalation) and Sodium nitrite
(IV)
⌠To pull the CN-ions away from cytochrome A ď
CNmethHb is converted to MethHb by using
specific oxidants
⌠MethHb indirectly competes with ferri-cytochrome
A to form a methHb-CN complex (non-toxic)
2. Sodium thiosulfate (IV) is given which reacts
with CNMethHb to form thiocyanate which is
harmless and is easily excreted in the urine
3. Hydroxycobalamine (orally) â which binds to CN to form
cyanocobalamine (non-toxic)
54. Formaldehyde
ďPungent odor ďUse as disinfectant
ďPreset in fabrics, in hemodialyzers
paper and ďSporocidal
construction ďPreparation of
materials vaccines
ďFormalin â 37%- ďPreservative
40% as disinfectant (embalming)
and tissue fixative ďIrritant (carcinogen)
which may contain
6-15% methanol as
stabilizer
55. Mechanism of toxicity Metabolism
ď Causes precipitation of ď Produces formic acid
proteins and will cause and may accumulate
coagulation necrosis of
exposed tissues and will result to
ď Gas is highly soluble in metabolic acidosis
liquids and when inhaled
produces immediate
local irritation of the
upper respiratory tract Toxic Dose: PEL of
and has been reported 1ppm; IDLH of 2ppm
to cause spasm and It has been reported
edema of the larynx that as little as 30 mL
of 37% formalin will
result to death
56. ď Gas exposure will produce irritations of the eyes
and inhalation can produce cough, wheezing
sounds and pulmonary edema
ď Ingestion may cause severe corrosive esophageal
and gastric injury, depending on the
concentration
⌠Metabolic acidosis may be cause by formic acid
accumulation from metabolism of formaldyhyde or
methanol
ď Hemolysis has occurred when formalin was
accidentally introduced into the blood through
contaminated hemodialysis equipment
Clinical Presentation
57. ďMethanol containing solutions â
administer ethanol and folic acid
ďFormate intoxication due to formaldehyde
alone be given folic acid
Treatment
58. ďWhen inhaled: remove patient from
exposure and give supplemental O2
ďSkin and eye: remove exposed clothing
and wash with running water and soap or
irrigate exposed eyes with copious normal
saline
ďIngestion: check and assess for gastric
injury ď perform gastric lavage; do not
force emesis
⌠Administer activated charcoal
Decontamination