PH 123.

1
Toxicology Laboratory | Prelim

HISTORY
Smith Papyrus (1600 B.C) Toxicity - decribes to the degree to which a
it cites the use of "charms against snake poisons". susbtance is poisonous ot can cause injury depends
on a variety of factors: dose, duration and route of
Mithridates VI King of Pontus exposure
credited to be the first to have developed antidotes.
took mixture of 36 ingredients as protection against Selective toxicity - means that a chemical will
assassination. produce injury to one kind of living matter without
survived each and any poisoning attempts. harming another form of life, even though the two
may exist close together.
Hippocrates
introduced clinical toxicology principles Safety - the probability that harm will not occur
bioavailability and overdose under specified conditions.

Dioscorides Adverse effects - are those that are damaging to

greek pharmacist who made the first attempt to classify
poisons (plants, animals and minerals)
de materia medica (5 volumes) with systematic description of
approximatelt 600 different plants and different medications.
Socrates
poison victim
executed by poison hemlock (active princple: coniine)
Philippus Aureolus Bombastus Theophrastus von Hohenheim
"Paracelsus"
All substances known to man are poison, there is none which is
not a poison and only the dose determines the effect"
Mathieu Joseph Bonaventure Orfila
Father of Modern Toxicology
used autopsy material and chemical analysis as proof of
poisoning
either the survival or normal function of the
individual
Hazard - likelihood that kinjury will occur in a given
situation or setting
Risk - expected frequency of the occurence of an
undesirable effect arising from exposure to a
chemical or physical agent.
Toxidromes - a group of signs, symptomes, and
laboratory findings that suggest a specific ingestion
LD50 - medial lethal dose
ED50 -median effective dose
Therapeutic Index = TD50/ED50

TOXICOLOGY LC 50 (Medial Lethal Concentration) - smallest

concentration that kills 50% of the population's
poisons administered through inhalation, aquatic
science of poisons
exposure.
defined as the branch of science that deals with poisons
"the study of the detection, occurence, properties, effects and
TLV (Threshold Limit Value) - maximum amount of
regulation of toxic substance"
drug considered safe; the lower the TLV, the more
study of the effect mechanism & treatment of poisons
danegous the substance

DEFINITION OF TERMS
Poison - any agent that may cause damage/injury/ death when
applied or developed inside the body

Toxins - a poisonous substance produced within living cells or

organisms.

Toxicant - a poison that is made by humans or that is put into the

enviroment by human activies. Example: Pesticides

Xenobiotic - any foreign substance not formally found in the

body

Poisoning - A clinical toxicity secondary to accidental exposure

Overdose - An intentional exposure with the intent of causing

self-injury or death.

Intoxication - Toxicity associated with any chemical substance JISON, Ana Barbara M | 3BSPH1
 PH 123.1
Toxicology Laboratory | Prelim

BRANCHES OF EFFECTS OF POISONS

TOXICOLOGY Local - effects can be seen at the site of application
Ex. Phenol - Corrosive, Irritants such as acids - inflammation
Clinical Toxicology
Remote - effects of poisons is distributed from point of entry
"Medical toxicology"
Ex. Atropine - eyes = mydriasis
deals w/the diagnosis & treatment of poisoning
observation of the signs & symptoms of poisoning
Systemic - the effects of poison is distributed from the point of
focuses on the effects of subtances in patients caused by
entry to systemic circulation
accidental poisonings or intentional overdoses of
medications, drug of abuse, household pridcts, ot various
Combination - the effects of poisons is distributed from the
other chemicals
point of entry to the systematic circulation.
Experimental Toxicology
FACTORS AFFECTING POISONING
Observation of toxic effects after adminstration to a
biological system.
A. POISON RELATED
Enviroment Toxicology
Concentration - the higher the concentration, the greater the
Deals with the identification or removal of toxicants from
toxic effect
the environment.

Solubility - the higher the lipophiicity, the higher the toxication

Regulatory Toxicology
Concern with safety testing of products to provide
Route of administration - intravenous: 100% F
information for regulatory compliance.
Concerned with the formulation of laws and regulations
B. PATIENT RELATED
authorized by laws, are intended to minimize the effect of
toxic chemicals on human health and the environment.
1. Age
Pediatrics
Mechanistic Toxicology
is not yet fully developed which may cause the
Deals with the mechanism of action pf the poisons
accumulation of drugs even when given at normal doses.
Under developed phase II metabolism (conjugation)
Descriptive Toxicology
developed phase I metabolism
Concerned with toxicity testing, which provides necessary
information for safety evaluation & regulatory requirement.
- Geriatrics
have slower metabolizing rates as compared to adults aged
Forensic Toxicology
20-40
Concerned with the medico-legal aspects of the harmful
effects of chemical on humans & animals
2. Habits
Smoking Cigarettes - Enzyme induction
Chemical Toxicology
Alcohol: Acute - Enzyme Inhibitor
Scientific discipline involving the study of structure and
Chronic - Enzyme inducer
mechanism related to toxic effects of chemical agents, and
encompasses technology advances in research related to
3. Tolerance
chemical aspects of toxicology.
receptors becomes "Desensitize"
reduction physical response
Occupational Toxicology
higher dose & frequency : cause an increase of toxic effect
Deals with the chemicals found in the workplace.
Industrial and agricultural workers (Ex.Handles pesticides)
4. Idiosyncrasy
usually affected
genetically determined
Industrial setting: Major route of poisoning (through
inhalation)
hemolytic Anemia - G6DP deficiency
determined by Coomb's tetst
POISONS
any agent that may cause serious damage/disease/injury/
death when applied or developed inside the body -
Paracelsus

JISON, Ana Barbara M | 3BSPH1

 PH 123.1
Toxicology Laboratory | Prelim

EVIDENCES OF
POISONING
Circumstantial Local vs. Systemic
from the event & site of poisoning
not reliable, not a strong evidence Local Effect
occurs at the site of first contact
Post-mortem "after death" bases - liquefactve necrosis
Corpus delecti Gases (chrlorine gas) - lung tissue
fathered after an autopsy is performed (examination of
tissues, organs, body fluids after death) Systematic Effect
reliable evidence fatal since the poison is absorbed and distributed in the
body
Experimental evidences
Done by administering the suspected substance to
some living animal to note the effects or symptom that
is very similar to the effects and symptoms of the poison.
POISONING EFFECTS
Acute
Chemical Evidence
prompt & there is marked disturbances of function or
Acquired by extracting body fluids from the patient &
death within a short perios of time
tested w/ specific reagent or chemical
high amount in short period of time

Symptomatic Evidence
Chronic
comparison of the established signs/symptoms with
gradual & there is progressive deterioration of the
that of the patient.
functioning of tissues
usually produced by talking small dose for a protracted
perios of time
SPECTRUM OF
Cumulative = toxic effects manifest when a certain limit
UNDESIRABLE is reached

EFFECTS Combined : Acute + Chronic

Phosphorus : Local effect: Cutaneous burns
Systemic effect: Hepatic and renal failure
Allergic Reactions
Chemical allergy: immunologically mediated adverse
reaction to a chemical
Resulting from previous sensitization to a chemical
Hypersensitivity: allergic state

Idiosyncratic Reactions
refers to a genetically determined abnormal reactivity to
a chemical
oversensitivity to the smallest dose or no effect even at
high doses.

Immediate vs, Delayed Toxicity

Immediate Toxicity
- toxicity within 24 hrs
- example: anaphylactic shock: worst form of allergy

Delayed Toxicity
- effect after a long period of time

Reversible vs. Irreversible

Reversible
- affected organ undergoes repair

Irreversible
- affected organ does not undergo repair JISON, Ana Barbara M | 3BSPH1
 PH 123.1
Toxicology Laboratory | Prelim

SPECIFIC EFFECTS

JISON, Ana Barbara M | 3BSPH1