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TOXICOLOGY AGE OF ENLIGHTMENT: Magendie (1783-1885),
History
MIDDLE AGES:
The writings of Maimonides (Moses ben Maimon A.D.
1135- 1204) included a treatise on the treatment of
poisonings from insects, snakes and mad dogs.
→ Maimonides → a significant individual, has several
writings which includes a treatise on the treatment of
poisoning coming from insects, snakes, and mad dogs
• He was the first one to introduce the concept of
bioavailability in which based on the forms of
o toxicants → the kind of substances
which once eat or drinks before
ingestion. This particular chemical can
be made more or less readily available
in the body, he conceptualized that
there are several substances which may
delay intestinal absorption such as
milk, butter, and cream, and he also
conceptualized that a full stomach may
also be responsible for delaying
absorption of a toxicants
RENAISSANCE PERIOD:
Philippus Aureolus Theophrastus Bombastus von
Hohenheim Paracelsus (1493- 1541) a physician-
alchemist, formulated many revolutionary views that
remain integral to the structure of toxicology,
pharmacology, and therapeutics today.
• More commonly known as Paracelsus
o He was responsible for many famous
sayings in toxicology
Quoted: “All substances are poisons; there is none
that is not a poison. The right dose differentiates a
poison from remedy”
→ This particular quote or sayings is now one of the
major foundations of to those response relationship in
toxicology
→ Paracelsus focus on the importance of what he calls
as:
• Toxicon → this is a particular toxic agent, and it
has a single chemical entity
Orfila (1787-1853), Bernard (1813- 1878) laid the
groundwork for pharmacology, experimental
therapeutics, and occupational toxicology.
➢ Orfila, a Spanish physician in the French
court, used autopsy material and chemical
analysis systematically as a legal proof of
poisoning.
o commonly known as the founder of
toxicology
➢ Magendie, a physician and experimental
physiologist, studied the mechanisms of
action of emetine (antiprotozoal that induces
vomiting) and strychnine (Antagonizes
glycine action causing loss of impulse
contractility in the spinal cord and brainstem).
o He detailed the absorption and
distribution of various compounds in the
body
➢ Bernard → responsible for studying the
pancreas as well as the liver and at the same
time he studies the physiological actions of
poisons specifically curare and carbon monoxide
gas
What is toxicology?
• the study of the effect of poisons on the
function of living systems
• Refers to the study of an adverse effect of
chemical, physical, or biological agents on living
organisms and the ecosystem including the
prevention as well as amelioration or treatment
of such adverse effect.
• Study of substances toxic to the body
• Common substances causing acute toxicity:
alcohol, acetaminophen, salicylate, abuse
substance and carbon monoxide
• Routes of exposure: ingestion, inhalation, and
transdermal absorption
Toxicologist- is trained to examine the nature of
those effects.
What is toxicity?
• The word “toxicity” describes the degree to
which a substance is poisonous or can
cause injury.
• The toxicity depends on a variety of
factors:
o Dose
o duration and route of exposure
o shape and structure of the chemical
itself
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o individual human factors
Fields of toxicology
→ Bishop enumerates the major 3 disciplines
→ Three major disciplines:
• mechanistic toxicology
• descriptive toxicology
• regulatory toxicology
→ And then the rest of the different fields enumerated
are considered to be different specialties within
toxicology
• Environmental Toxicology
• Occupational (Industrial) Toxicology
• Regulatory Toxicology
• Food Toxicology
• Clinical Toxicology
• Descriptive Toxicology
• Forensic Toxicology
• Analytical toxicology
• Mechanistic Toxicology
• Reproductive Toxicology
• Developmental toxicology
Environmental Toxicology
→ This includes the evaluation of environmental
chemical pollutants and its effect on the human health.
• Is concerned with the study of chemicals that
contaminate food water, soil, or the
atmosphere.
• It also deals with toxic substances that enter
bodies of waters such as lakes, streams,
rivers and oceans.
• This sub-discipline addresses the question of
how various plants, animals, and humans are
affected by exposure to toxic substances.
→ Currently, because of what is happening in our
surroundings, this is now a growing area of concern as
we further learn the different action of this chemicals.
→ Goal of the environmental toxicology, is to monitor the
different occupational health issues, like for example
before the miners they were given very minimal personal
protective equipment mostly focusing on the possible
physical injuries, but currently it is now more improved,
and they are much strict on the requirements on such
because they are more exposed and their line of work
exposed system to several compound which are toxic to
the body.
→ What we are studying about the toxicity of different
compound helps in increasing public health
biomonitoring effort.
• This helps us to identify what may be present in
the environment which are considered to be
toxic in order for us to at least pass a law or to
create guidelines on how we could properly
utilize and to avoid significant impacts of this
toxic compounds to the society.
Occupational (Industrial) Toxicology
• Is concerned with health effects from
exposure to chemicals in the workplace.
→ Here in the Philippines, one of the significant offices
which is responsible for ensuring the safe and healthy
work environment would be OSHA (occupational safety
and health administration).
OSHA
• responsible for creating guidelines on how to
ensure that there is a safe work environment on
the different fields or different types of
occupation here in the Philippines.
• They are the one responsible for training safety
officers for them to identify what are the possible
risks, possible hazards present in their line of
work, and to create a particular control measure
and action plan if there would be any exposure
to such hazardous compounds.
• This field grew out of a need to protect
workers from toxic substances and to make
their work environment safe.
Regulatory Toxicology
→ Uses combined data from the mechanistic and
descriptive, in which they used the data to establish a
standard which will define the level of safe exposure.
• Gathers and evaluates existing toxicological
information to establish concentration-based
standards of “safe” exposure.
• The standard is the level of a chemical that a
person can be exposed to without any
harmful health effects.
→ Typically, those who are working as a regulator
toxicologist they work in conjunction with the regulatory
body in a particular country, they may be here in the
Philippines, they may be the one working our food and
drug administration (FDA) who’s responsible for
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regulating and for providing approval for the utilization
and control of consumption of different foods and drugs.
→ They are the one responsible in ensuring that
everything that we utilize everything we are eating,
taking should not pose a risk to public health and safety.
Food Toxicology
→ specific for ensuring the safety in terms of the food we
ingest would be the food toxicology.
• Is involved in delivering a safe and edible
supply of food to the consumer.
→ Usually everything we eat, the process one may be
containing several substances to make it look, taste, and
smell better.
• MAIN FOCUS OF FOOD TOXICOLOGY → During
processing, a number of substances may be
added to food to make it look, taste, or smell
better. Fats, oils, sugars, starches and other
substances may be added to change the
texture and taste of food. All of these
additives are studied to determine if what
amount, they may produce adverse effects.
• A second area of interest includes food
allergies. For example, many people have
trouble digesting milk, and are lactose
intolerant.
→ We now have a part of the regulation in the food
industry is to ensure that consumers are made aware of
what are the possible food allergen to the food we are
eaten. There would be a warning always on the label of
the different food products on what are the possible
allergens content of that particular product.
• Toxic substances such as pesticides may
be applied to a food crop in the field, while
lead, arsenic, and cadmium are naturally
present in soil and water, and may be
absorbed by plants. Toxicologists must
determine the acceptable daily intake level
for those substances.
→ to know on how much, they will put in the pesticide up
until in what particular number of weeks prior to harvest
or when is the time that the plants will have no exposure
to the pesticide
Clinical Toxicology
→ Focuses on the relationship between xenobiotics and
disease states.
• Concerned with diseases and illnesses
associated with both (acute and chronic)
short term or long-term exposure to toxic
chemicals.
• Clinical toxicologists include emergency
room physicians who must be familiar with
the symptoms associated with exposure to a
wide variety of toxic substances in order to
administer the appropriate treatment.
→ Involves medical personnel specifically physicians and
toxicologist who are familiar with the different symptoms
associated with exposure to a variety of toxic substances
in order to administer the appropriate treatment
→ Toxicologist do have 2 significant focus:
• how to determine using diagnostic testing
• how to determine what type of toxic compound
has been ingested by the patient as well as
therapeutic interventions.
→ For example: we have several cases of accidental
poisoning or deliberate poisoning or a suicide attempts
which involves the used of a chemical compound so they
are the one responsible for responding,
• first what would be the first aid which given to
the patient if suspected to have had poisoning
and then eventually to perform laboratory test to
determine what particular type of compound has
been the cause of toxicity for them to determine
or to be able to identify what must be the correct
therapeutic intervention.
Descriptive Toxicology
• Is concerned with gathering toxicological
information from animal experimentation.
→ Coming from research studies using test animals, they
used the results from the animal experiment to predict
what level of exposure would be considered as harmful
for humans
➢ they relate that whatever were the result of the
test using animals they will use this data to
determine what may be the possible level of
exposure which could be posing a risk or threat
for human.
o This particular process is known as
“RISK ASSESSMENT”
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• These types of experiments are used to
establish how much of a chemical would
cause illness or death.
→ How much is the dose is to cause harmful effect to
humans.
Forensic Toxicology
• Is used to help establish cause and effect
relationships between exposure to a drug
or chemical and the toxic or lethal effects
that result from that exposure.
→ Primarily concern both with the medical and legal
aspects or consequences of exposure to chemicals or
drugs.
➢ uses if there have been cases of possible
poisoning, deliberate poisoning, this is being
studied to determine how to be able to
differentiate the accidental one from those which
might be premeditated type murder.
→ MAJOR FOCUS: establish and validate the different
performance of the different analytic methods for us to be
able to generate possible evidence.
→ This may be use for a legal situation which would be
including the cause of death of the victim.
Analytical Toxicology
→ The one where our laboratory testing would be
focusing into
→ Concern with the identification of toxicant based on
the analysis of the different body fluids such as (blood,
urine) as well as other compounds such as stomach
content, excrement, or skin.
• Identifies the toxicant through analysis of
body fluids, stomach content, excrement, or
skin.
Mechanistic Toxicology
• Makes observations on how toxic
substances cause their effects.
→ This elucidates the cellular, molecular, and the
biochemical effects of our xenobiotics within the context
of the dose-response relationship → this would be
focusing on the xenobiotic itself and its adverse effects
Data gathered in the mechanistic toxicology → provides a
basis for the rational therapy design to know how much
particular treatment will give to the particular individual
who is been exposed to toxic compounds as well as the
development of laboratory tests to assess the degree of
exposure or what we called dosage of an individual.
• The effects of exposure can depend on a
number of factors based on the
characteristic of the toxicants or the
xenobiotics, including the size of the
molecule, the specific tissue type or cellular
components affected, whether the
substance is easily dissolved in water or
fatty tissues, all of which are important when
trying to determine the way a toxic
substance causes harm, and whether
effects seen in animals can be expected in
humans.
What is Toxic?
• This term relates to poisonous or deadly
effects on the body by inhalation
(breathing), ingestion (eating), or
absorption, or by direct contact with a
chemical.
TOXICANT
• A toxicant is any chemical that can injure
or kill humans, animals, or plants, a
poison.
• The term “toxicant” is used when talking
about toxic substances that are produced by
or are a by-product of human-made
activities.
▪ Generated by humans
Toxin
• The term “toxin” usually is used when talking
about toxic substances produced naturally.
According to Bishop, there are 3 different terms
which are being used interchangeably in
toxicology:
• Xenobiotic – chemicals and drugs not
normally found or produced in the body
exogenous agents (xeno means “outside”
and bio means “life”)
▪ can have adverse effects on
living organism
▪ this term is more often used
to describe environmental
exposure to different
chemicals and drugs such as
antibiotics,
antidepressants, and some
compounds such as
perfluorinated and
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brominated compounds
(xenobiotic agents)
• Bishop: “Toxicology is a study of adverse
effects of xenobiotics in humans
• Poison – harmful effects to the body
o exogenous agents that have an
adverse effect on a biological
system.
o directly from an animal, plant,
mineral or gas. (e.g., venom from
poisonous snakes or other
poisonous animals, plants such as
hemlock)
• Toxins – endogenous substance = they
are created inside, or they are biologically
synthesized in a living cell or a
microorganism such as botulinum toxin
(from clostridium botulinum), as well as
other toxins produced by different bacteria,
mycotoxins from fungi. - hemotoxins
produced from venomous snakes
ADVERSE EFFECT
• those that are damaging to either the
survival or normal function of the
individual.
• dependent upon the concentration/ dosage of
active compound at the target site for a
sufficient time (exposure)
Tolerance → responsiveness
• The more tolerant a person is for a particular
chemical there is a state of decreased
responsiveness to a toxic effect of a
chemical resulting from a prior exposure to
that chemical or structurally related
chemical.
• Example: Alcohol tolerance – different
individuals would have different levels of
tolerance. (Low or high depending on their
body function)
Target Organs: adverse effect is dependent upon
the concentration of active compound at the target
site for enough time
• One of the significant focus
• Distribution is not equal of toxic compounds
in the different cells or tissues in the body
• There are compounds which would be
concentrated more on a particular organ.
• There are organs which are readily absorbed
coming from different routes of exposure.
• Not all organs are affected equally
o greater susceptibility of the target
organ - where it will mostly
accumulate – drastic impact of
chemical on that organ.
o higher concentration of active
compound
• 2 major organs which are considered to
be mostly the target organs: → mostly
processed this compound
o Liver
o Kidney
• Liver → high blood flow, oxidative reactions
o First pass – everything you have
ingested or absorbed would be first
passing through the liver.
o First to filter before it goes towards
the blood circulation.
o Liver is exposed to high oxidative
reactions.
o where xenobiotic
biotransformation occurs
xenobiotic biotransformation – pertains to the
transformation occurring in a chemical caused by the
activity/capability of hepatocytes specifically through
the action of cytochrome P450 isoenzyme to induce
different chemical processes.
➢ Example: converting compounds from a
hydrophobic into a hydrophilic compound
(lipid loving – may only be absorbed or bind
itself with lipid containing products,
substances, organic compounds, organic
solvents in the blood)
▪ Upon transformation, it is
converted to a hydrophilic =
non-polar compound to
polar compound
▪ It could be readily mix with
the blood in order to be more
excretable.
▪ The more capable the
compound to be joining the
blood circulation (since it is a
polar compound and already
miscible with water), the
body becomes more capable
to excrete compounds
through urination.
• Kidney → high blood flow, concentrates
chemicals
o Filters out toxic compounds for the
excretion through urine.
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• Lung--high blood flow, site of exposure
o Several chemicals which may be
absorbed in the lungs
o Through exhalation = byproducts are
removed
• Other tissues affected:
o Cardiac muscle
o bone marrow
o neurons
• Neurons--oxygen dependent, irreversible
damage
• Myocardium--oxygen dependent
• Bone marrow, intestinal mucosa--rapid
divide
Target Sites: Mechanisms of Action
• Adverse effects can occur at the level of the
molecule (molecular level), cell (cytotoxic),
organ, or organism
• Molecularly, chemical can interact with:
o Proteins
o Lipids
o DNA
• Cellularly, chemical can
o interference with receptor-ligand
binding
o interference with membrane function
o interfere with cellular energy
production
o bind to biomolecules
o perturb / disturb homeostasis (Ca)
Dose
• The amount of chemical entering the body
• This is usually given as mg of chemical/kg
of body weight = mg/kg (mass of the
substance per kilogram of the body weight)
• The dose is dependent upon
o The environmental concentration
(presence of xenobiotic compound
from the source)
o The properties of the toxicant
o The frequency of exposure
o The length of exposure
o The exposure pathway (route of
exposure)
What is a Response? The degree and spectra of
responses depend upon the dose and the organism
→ describe exposure conditions with description of
dose
• Change from normal state
o could be on the molecular, cellular,
organ, or organism level--the
symptoms
• Local vs. Systemic (general)
o Local – e.g., discoloration of the skin
o Systemic – e.g., fever
• Reversible vs. Irreversible
o Reversible – goes back to normal
state
o Irreversible – does not go back in its
normal state
• Immediate vs. Delayed
• Graded vs. Quantal
o degrees of the same damage vs. all
or none
o Graded – increasing response and
increasing dose and the changes
happening in each increase in terms
of response and dose. (e.g., blood
pressure, temperature)
o Quantal – all or nothing, a dose that
is considered lethal or fatal to an
individual.
▪ Quantal dose response –
shows a specific response at
a progressively increasing
dose.
Dose-Response Relationship: As the dose of a
toxicant increases, so does the response.
• The higher the dosage, effect is more
prominent and adverse.
• Dose determines the biological response.
RESPONSE
0-1 NOAEL (No Observed Adverse Effect Level) –
low dose, low response
- As the number goes up, as the dose
increases, the response would also
increase.
2-3 Linear Range – consistent increase
4 Maximum Response – peak
- Further exposure or for the increasing of
dose would no longer have significant
effect if it already kills the living organism
- Response would stop if the organism
dies.
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ng/mL Normally expressed as nanograms of
substance per liter of air or water (or as ppm)

Exposure: Pathways

Routes and Sites of Exposure

• Ingestion (Gastrointestinal Tract)

• Inhalation (Lungs)
DOSE DETERMINES THE BIOLOGICAL • Dermal/Topical (Skin)
RESPONSE • Injection
o Intravenous (direct to blood vessels),
Measures of Toxicity: The Toxic Dose intramuscular, intraperitoneal
• Typical Effectiveness of Route of
Toxic dose – pertains to the amount of a compound
Exposure: iv > inhale > ip > im > ingest >
which would be eliciting or producing a toxic
topical
response or toxicity
o IV (Intravenous) – most effective
TD50 The amount (dose) of a chemical which o Inhalation
produces toxic response in 50% of a population of o Intraperitoneal
test animals to which it is administered by any of a o Intramuscular
variety of methods o Ingestion
o Topical – least effective
mg/kg Normally expressed as milligrams of • Effectiveness varies according to how a
substance per kilogram of animal body weight certain compound could easily affect the
body of the living organism exposed to such
Measures of Toxicity: The Median Lethal Dose -
compounds.
level which may be causing death, lethal or fatal to
test animal The easier it is to enter the blood circulation is
more effective.
LD50 The amount (dose) of a chemical which
produces death in 50% of a population of test • Skin contact – have certain barriers and we
animals to which it is administered by any of a variety have more defense mechanisms inside the
of methods body.
mg/kg Normally expressed as milligrams of o The more defense mechanisms
substance per kilogram of animal body weight present, the least effectiveness.

Measures of Toxicity: The Median Lethal Duration of Exposure – how long is the living
Concentration - pertains to the concentration of a organism exposed to toxic compounds
chemical in an environment which could produce Three terms are commonly used to describe the
death in 50% of exposed population duration of dose(s)
LC50 The concentration of a chemical in an • Acute
environment (generally air or water) which produces • Chronic
death in 50% of an exposed population of test
• Subchronic
animals in a specified time frame
Duration of Exposure: pertains to how long should
mg/L Normally expressed as milligrams of substance
the exposure be before toxic symptoms would exhibit
per liter of air or water (or as ppm part per million) -
in the body of the organism exposed to the toxic
depending on the route of administration
compound.
Measures of Toxicity: The Effective Dose
Acute Exposure
ED50 The amount (dose) of a chemical that would be
• Acute - immediate
predicted to be effective or have a therapeutic benefit
• Application of a single or short-term
in 50% of a population of test animals to which it is
(generally less than a day) dosing by a
administered by any of a variety of methods
chemical
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• If toxic symptoms are expressed, they are
referred to as symptoms of “acute toxicity”
o E.g., allergic to peanut – few
minutes after eating (automatically
the symptoms will appear - difficulty
in breathing)
Chronic Exposure
• There must be a repeated exposure.
• A single dose would not be sufficient enough
to elicit for the toxic symptoms to occur.
• Time frame as to when the toxic symptoms
occur= significant
• Expression of toxic symptoms only after
repeated exposure to a chemical in doses
regularly applied to the organism for a time
greater than half of its life-expectancy
• If toxic symptoms are expressed, they are
referred to as symptoms of “chronic
toxicity”
Subchronic Exposure
• SIMILARITY WITH CHRONINC: Together
with chronic exposure, they both require
multiple exposure prior to appearance of the
symptoms.
• In between of acute and chronic exposure.
• DIFFERENCE: Toxic symptoms are
expressed after repeated applications for a
timeframe less than half the life
expectancy of the organism – but more
often than a single dose or multiple doses
applied for only a short time
• If toxic symptoms are expressed, they are
referred to as symptoms of “subchronic
toxicity”
Exposure: Duration
• Acute = < 24 hours = usually 1 / single
exposure
o Appearance of the toxic symptoms
would occur immediately
o A single exposure would suffice
o If the signs and symptoms occur
within a day, we consider it as acute
toxicity.
• Subacute = 1 month = repeated doses
o Not within a day but not that long to
be considered chronic or subchronic.
o Require repeated dose like chronic
or subchronic
o About a month for the signs and
symptoms to appear.
• Subchronic = 1-3 months = repeated doses
• Chronic = > 3 months = repeated doses
• Subacute, subchronic, and chronic = all
require multiple dosage or repeated
exposure
• Acute = single exposure
• In terms of duration:
o Acute – within a day
o Subacute – more than a day but
less than a month or within the
month
o Subchronic – 1 to 3 months
o Chronic - more than 3 months
• In terms of exposure: vary depending on
the coping mechanism of the body
Over time, the amount of chemical in the body can
build up (common in lipophilic compounds – not
readily excretable by the body), it can redistribute, or
it can overwhelm repair and removal mechanisms
• Lipophilic – lipid loving, non-polar
compounds and tend to accumulate in
tissues which has the capability to take up fat
and binds in fat tissues that could cause
build-up.
• Once cells and tissues, organs are
overwhelmed, toxic symptoms would appear.
ADME: Absorption, Distribution, Metabolism, and
Excretion
• Once a living organism has been exposed to
a toxicant, the compound must get into the
body and to its target site in an active
form in order to cause an adverse effect.
• The body has defenses:
o Membrane barriers (skin, hair)
▪ Membrane barriers- does
not only include the external
barriers but would also be
pertaining to internal barriers
or present in the cells,
different tissues, and organs.
o Skin being intact would prevent
immediate exposure to several toxic
compounds.
o The absorption of cells would also be
dependent upon how this would be
transported, on whether your cells
could readily take up these
compounds through:
▪ passive and facilitated
diffusion, active transport
(carrier compound)
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o Biotransformation enzymes,
antioxidants
▪ Biotransformation –
capability to convert
compounds to less
hazardous ones (P450
isoenzyme) so it could
undergo different chemical
reactions or it could undergo
changes (e.g., lipophilic to
hydrophilic)
▪ Antioxidants – prevents
further damage in the cells
o Elimination mechanisms
▪ Elimination/excretion
mechanism
▪ The need for you to excrete
a particular compound
through saliva, tears, urine
(common), and fecal
elimination.
▪ Our body is also capable not
only in causing or accepting
adverse effects but also to
excrete
unnecessary/unwanted
compounds in the body.
Absorption: ability of a chemical to enter the blood
(blood is in equilibrium with tissues)
• Effectivity vary depending on the route of
exposure.
• Inhalation-- readily absorb gases into the
blood stream via the alveoli. (Large alveolar
surface, high blood flow, and proximity of
blood to alveolar air) – the more exposed it is
to blood circulation, the easier it is to enter
the target organ.
o Most potent ones are obtained
through inhalation
o Most potent of entry is through the
circulatory system
o Gases = Lungs = alveoli = blood
circulation
• Ingestion-- absorption through GI tract
stomach (acids), small intestine (long contact
time, large surface area--villi; bases and
transporters for others)
o 1st Pass Effect (liver can modify) –
states that all compounds which are
absorbed by the GI tract through the
microvilli of the small intestine would
first pass through the liver and from
the liver it could further detoxify
compound.
o Liver – first to filter compounds
absorbed by the body through
ingestion
• Dermal--absorption through epidermis
(stratum corneum), then dermis; site and
condition of skin
o Least effective
o If the skin is intact, it is less likely to
enter blood circulation because
compounds will not readily pass
through but if there are breakage and
open wounds that would be a good
area/point of entry for toxic
compounds.
Distribution: the process in which a chemical agent
translocated throughout the body
• Distribution – how a particular compound is
being capable of moving from the route of
exposure towards the blood circulation and
towards the target site.
• Blood – most potent carrier
o Blood carries the agent to and from
its site of action, storage depots,
organs of transformation/metabolism,
and organs of elimination
• Blood elimination through kidney
• Rate of distribution (rapid) dependent
upon:
o blood flow
o characteristics of toxicant (affinity for
the tissue, and the partition
coefficient)
▪ Partition coefficient –
pertains to the property of a
particular compound or
chemical substance to
distribute itself between two
immiscible phases.
• Distribution may change over time
o Depends upon bodily reactions or
your body’s defense mechanism.
DISTRIBUTION: STORAGE AND BINDING
• Storage in Adipose tissue-- Very lipophilic
compounds (DDT) will store in fat. Rapid
mobilization of the fat (starvation) can rapidly
increase blood concentration
o e.g., pesticides
o immiscible in water (lipophilic) –
since it is lipophilic it is also
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hydrophobic and not immediately
eliminated
o starvation – our body would tend to
undergo gluconeogenesis in which it
would induce or one of the
mechanisms would be lipolysis or
would be getting energy coming from
fat sources – content inside will be
mobilized and redistributed
• Storage in Bone-- Chemicals analogous to
Calcium-- Fluoride, Lead, Strontium
• Binding to Plasma proteins-- can displace
endogenous compounds. Only the free
plasma proteins would be made available for
adverse effects or excretion
o Usually compounds which would be
requiring carrier proteins.
o Competition among endogenous
compounds and in terms of toxic
compounds which may be also
requiring this carrier proteins.
Metabolism: adverse effect depends on the
concentration of active compound at the target site
over time
→ This is where modification of the toxic compound
could occur, usually this occurs through different
chemical and enzymatic reaction.
• The process by which the administered
chemical (parent compounds) are modified
by the organism by enzymatic reactions.
• Primary objective-- make chemical agents
more water soluble and easier to excrete
→ From hydrophobic into a hydrophilic
compound, and the purpose of that is to
make it readily more excretable
o decrease lipid solubility -->
decrease amount at target
→ Most of all if the target site is, so this is a
lipophilic compound in which the target site is
tissue cells would also be containing the
compounds where it mostly binds, so if it is
already converted to a hydrophilic one then it
will not further accumulate
o increase ionization --> increase
excretion rate --> decrease toxicity
→ Increase in ionization and changed
in the polarity or change in the solubility
of that particular compound making it
more miscible with water making our
body easier or making our kidneys more
effective in excreting this compound
→ The more easier for our body it is to excrete this
compound, there would also be a decrease in the toxicity.
• Bioactivation-- Biotransformation can result
in the formation of reactive metabolites
→ This is a biotransformation which could result in the
formation of reactive metabolites as a product of the
biotransformation
→ The only problem with this bioactivation as an end
product after biotransformation is that its bioactivation
could result into a formation of a harmful or a highly
reactive metabolic compound.
→ Other term used in bioactivation is toxication.
Excretion: Toxicants are eliminated from the body by
several routes
→ Elimination could be through different mechanisms
• Urinary excretion → Primary method of
elimination/ excretion → most common
o water soluble products are filtered
out of the blood by the kidney and
excreted into the urine
→ But the first to be damaged if the kidney is acting too
much is the glomerular function of the kidney.
→ The kidney would filter out unwanted compounds and
further excreted in the urine
• Exhalation
o Volatile compounds are exhaled by
breathing
→ Some compounds can be eliminated through
exhalation, usually the involve here would be
volatile compound such as alcohol.
→ They are readily exhaled by breathing
• Biliary Excretion via Fecal Excretion
o Compounds can be extracted by the
liver and excreted into the bile. The
bile drains into the small intestine
and is eliminated in the feces.
→ Compound, which is extracted by the
liver, the one that take up and transform by
the liver would be further excreted through
bile, and this bile would be drain in the
small intestine and would proceed in the
duodenum of the intestine and would further
eliminated (because the content of the small
intestine would proceed to the large
11 | C C 2 L E C 1 4 I N T R O T O T O X I - E T H A N O L
intestine) which would now responsible for
the formation of the stool or feces.
• Milk, Sweat, Saliva
→ would also be excreted for mothers who are
currently breastfeeding, if the mother is exposed to a
toxic compound like for example there is a too much
fluoride in the water they’re drinking or to those
water supply. A compound which may be very small
usually the trace elements, they could readily pass
through or can be excreted through the milk.
→ Some may also be eliminated through sweat as
well as saliva
Biotransformation
→ One of the metabolic processes which occurs inside
the body whenever toxic compounds is present
• Key organs in biotransformation
o LIVER (high) → Primary organ involve
because it is present in the liver and
one the primary responsibility or
function of the hepatocytes, remember
the biochemical hepatocytic system,
reticuloendothelial system which are
primarily responsible for the
metabolizing and detoxification of
blood.
→ Liver also is the first pass, so everything we ingest,
everything that may be harmful before it is transfer to the
blood circulation, the GIT will first put this towards in the
liver through the portal fin.
o Lung, Kidney, Intestine (medium)
→ Basically, this also the one involved in ADME
(Absorption, Distribution, Metabolism, and Excretion) so
it depends if first where is the point of entry, so
sometimes in the point of entry we already have defense
mechanisms
o Others (low)
• Biotransformation Pathways
o Phase I-- make the toxicant more
water soluble
▪ transformation of a
hydrophobic compound into a
hydrophilic compound to make
it more excretable
o Phase II-- Links with a soluble
endogenous agent (conjugation)
→ If it needs further requirement to have a
compound that will help in eliminating
compounds which are harmful to the body,
we link it or bind it with an endogenous
agent so it would bind itself together like for
example the toxic compounds which will
bind with the bile which would further be
eliminated through fecal elimination. So, it
depends upon the characteristics and where
does it undergo transformation. Either the
compound itself or with the need of other
endogenous compound present in the body.
Biotransformation (Metabolism)
• Can drastically affect the rate of clearance of
compounds
→ The more capable our body is in converting a
particular compound into a more excretable form, the
easier it is for our tissues and organ to eliminate this
compound
• Can occur at any point during the
compound’s journey within the body starting
from absorption to excretion
Compound Without With
Metabolism Metabolism
Ethanol 4 weeks 10mL/hr
Phenobarbital 5 months 8hrs
DDT- (dichloro- infinity Days to weeks
diphenyl-
trichloroethane)
→ Shows example of compounds, the differentiation in
terms of how long it will stay in the body with or without
metabolism
→ Ethanol – which would stay in the body supposedly for
about 4 weeks if metabolism doesn’t normally occur but if
metabolism occur, the body will eliminate ethanol at a
rate of 10 mL/hr
→ Phenobarbital – it could stay in the blood or its in the
body for about 5 months but due to metabolism it would
only stay, or it could be eliminated after 8 hrs
→ DDT (dichloro-diphenyl-trichloroethane) pesticide –
could remain since it is a lipophilic compound could
remain in the different cells in the body containing high
amount of fats, until that particular organism dies, it’s for
infinity but due to the capability of the body to metabolize
this compound it could only last for up to days or weeks
12 | C C 2 L E C 1 4 I N T R O T O T O X I - E T H A N O L
Individual Susceptibility --there can be 10-30-fold
difference in response to a toxicant in a population
→ Other factor which may affect toxicity in a living
organism would be the individual susceptibility. Although
we do have identified certain duration in terms of
adsorption, distribution, metabolism, and elimination of
compound there would still be difference there can be
about 10-30-fold in response to a particular toxicant in a
population.
What may be causing this variation?
→ Genetics-species – for example if you would be
comparing our metabolism of alcoholic drinks here in the
Philippines, if you would be comparing Filipinos to
Germans or to those countries who are drinking alcohol
on a daily basis as part of their daily intake then of course
we do have different number of hours in terms of
metabolism or mechanism in terms of the ADME
characteristic for ethanol
→ Strain variation – of a particular group of organisms
→ Interindividual variation among living organisms
• Genetics-species, strain variation,
interindividual variations (yet still can
extrapolate between mammals--similar
biological mechanisms)
• Gender (gasoline nephrotoxic in male mice
only)
→ Another difference is the gender, for example between
males and females they have different metabolism rate of
metabolism of alcoholic drink
• Age - young (old too)
o underdeveloped excretory
mechanisms
o underdeveloped biotransformation
enzymes
o underdeveloped blood-brain barrier
→ There would also be a difference between the age
group then, for example the younger groups their ADME
characteristic might be different due to underdeveloped
mechanisms in the body so underdeveloped excretory,
biotransformation enzyme, as well as underdeveloped
blood-brain-barrier.
→ If you would be comparing the metabolism as
compared to adults.
→ TAKE NOTE: the individual susceptibility doesn’t only
focus on the susceptibility, but all throughout the process
starting from the absorption to elimination
Individual Susceptibility
• Age- old
o changes in excretion and metabolism
rates, body fat
• Nutritional status → because this could also
affect the different mechanisms including also
the defense mechanism of the body as well as
the general health condition of an individual
• Health conditions → For example if you
would be comparing the capability of the liver to
do a biotransformation between an individual
who still does have a normally functioning and
healthy liver as compared to somebody who do
already have a fatty liver due to chronic
alcoholism, they would of course has a
difference
• Previous or Concurrent Exposures
o Additive- antagonistic
o synergistic
→ Some compound may become an additive, so it can
adds up to the adverse effect of the particular toxic
compound it could be synergistic or the reason why you
have that particular effect because of the presence of a
particular compound or may be antagonistic it might not
be occurred, or the particular effect doesn’t manifest due
to the presence of antagonist.
EFFECTS
→ There would also a variation in terms of effects. There
would be differences in terms of when effects would
manifest will this be immediately present, or the effects
would occur or manifest after few years.
• Acute Effects: rapidly developing, reaching
a maximum with severe symptoms.
o Example: exposure to high doses of
CN- will kill within a few minutes
→ The same with toxicity, acute are those effects of
exposure to toxicants or toxic compounds which is
xenobiotic in which the effects were rapid developing
such as is this would be immediately lethal after a few
minutes of exposure or would this elicit immediately
gastrointestinal symptoms after intake for example
ingestion of our route of exposure so if the effect is
immediate that is what we called acute effect
• Subacute Effects: symptoms generally not
as severe, but toxic effects often same as
acute.
→ This would take longer periods of time before the
effect would occur, but again the symptoms might not be
13 | C C 2 L E C 1 4 I N T R O T O T O X I - E T H A N O L
generally a severe, but the symptoms would have toxic
effect the same with the acute
• Chronic Effects: progresses at a slow and
varying rate; may be mistaken for other
diseases. Often difficult to determine cause-
and-effect unless in laboratory....
o Example: asbestos-caused cancer
may be delayed 20-30 years.
▪ NOTE: acute exposure may
result in either acute or
chronic effects.
→ It would take months or actually years before the
effects would manifest so it progresses at a slow and
varying rate, and sometimes the problem would be that
this might be mistaken for other disease.
✓ For example, those who is exposed to mining
industry they may eventually developed a lung
cancer after some time, even the community
living on areas which are consuming
contaminated bodies of water and products /
food and other dietary intake which may also be
contaminated, the effects of it might not be
generally appear immediately but it would run
through several generation.
→ We have been able to distinguish between acute
exposure and the effects itself, take note that there might
be an acute exposure that can result to further immediate
sign and symptoms but aside from the immediate toxic
symptoms there might be a chronic effect, so it
sometimes happens. In a single exposure there might be
a particular toxic symptom but after few years you can
have another condition which was initially or the one
initiate it would be the acute exposure. That is why for
those individuals working who’s exposed to radiation, we
are typically keeping their records for about 30 years in
incase they might be develop a disease such as cancer
which are correlated with their line of work, they might be
compensate for such.
• Accumulative Effects: occurs two ways...
accumulation of toxin: exposure to heavy
metals (lead, mercury) that have long half-
lives result in disease due to metal
accumulation OR accumulation of effect:
low level exposure to organophosphate
pesticides depresses acetylcholine esterase
to a point where symptoms occur.
→ In accumulative effects either the compound is
accumulating which might be causing the adverse effect
such as accumulation of toxins.
✓ For example, you are exposed to a particular
chemical that you are mostly getting due to
ingestion like for example somebody is
contaminating your food or your water is might
be exposed and contaminated with excess
amount of fluoride so the continuous exposure
might cause accumulation of that toxins so the
toxin itself will accumulate. The symptoms can
also be the one to accumulate the effects such
as you’ve only had low level of exposure to
pesticide containing organophosphate (this
would affect our acetylcholine, esterase) and
eventually even if you have a single dose
exposure but the effects are put layer by layer
eventually that would be led to manifestation of
toxic symptoms
• Delayed Effects: effect may occur only
after long exposure; agent cannot be found
in blood or tissues. Damage to system
already done
o Example: radiation sickness
→ Effects could be delayed so effects which occur just
like chronic, effects should occur after a long exposure
where in intime the agent could no longer be found in
blood or tissues but there is already damage to the
system. So maybe you already stop to that exposure from
those particular toxicants, but continuously your system
is or the damage is continuous as a delayed effect of that
exposure such as again the radiation sickness
CLASSIFICATION OF TOXIC AGENT
→ There are several classifications. This toxic agent
could be classified according to
Classification by....
• Use: pesticides (atrazine), solvents
(benzene), food additives (nutra sweet)
→ Maybe it depends on the exposure we have on how do
we utilize compounds or how do we utilize this toxicants,
could either be group of toxic compounds falling under
pesticides, solvents, food additives, or maybe they are
classified according to their effects which of this
particular toxic agents are considered to be carcinogen,
the one who can cause cancer or mutagen which would
possibly be eliciting mutations in the DNA sequence in
the cell or who is targeting liver our hepatotoxicants or
the one who has damaging effect to the hepatocytes
• Effects: carcinogen (benzo-a-pyrene),
mutagen (methylnitrosamine),
hepatotoxicant (CHCl3 - chloroform)
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• Physical state: oxidant (ozone), gas (CO2 → For alcoholic drinks in ethanol, our threshold
– carbon dioxide), dust (Fe2O3 – iron oxide),
liquid (H2O- water)
→ Could also be based on the characteristic or the
physical state of the compound itself. Is it the oxidant, is
it in the form of gas, liquid, or dust?
• Chemistry: aromatic amine (aniline),
halogenated hydrocarbon (methylene
chloride)
→ Could also be in the chemical group or chemical
characteristic according to chemistry, so we have groups
of toxic agents which are falling under aromatic amine of
those halogenated hydrocarbon, and this could also be
classified according to mechanism of action which among
the toxic agents are affecting the cholinesterase who is
the methemoglobin producer and so on and so forth.
• Mechanism: cholinesterase inhibitor
(malathion), methemoglobin producer
(nitrite)
→ Take note that the terms of our classification in terms
to those classification we are using, our groupings would
be based on what is the particular classification
according to the type of compound.
TOXICOLOGY OF SPECIFIC AGENTS
TOXIC AGENTS / CHEMICAL AGENTS
A. ALCOHOLS
→ other forms of alcohol which may have significant toxic
effects to living organisms or more specifically for
humans
• Are common central nervous system
(CNS) depressants → That is why for
example if you would take an alcoholic drink,
you would have, when you reach a certain level,
you will be having an urge to sleep and even a
toxic level it can lead to loss of consciousness
• Toxic effects are both general and
specific. → systemic/ local
• Alcohol could cause disorientation,
euphoria, confusion, and toxic symptoms
may progress to unconsciousness, paralysis
and even death.
• Symptoms of alcohol intoxication begins
when you go beyond the threshold limit in which
at this particular level it is having a significant
symptom → concentration of 0.05% w/v
(>50 mg/dL blood alcohol)
consumption or actually it is not totally the limit of an
individual but rather in terms of legal aspect of
statutory limit our level is .05% (equivalent to a
concentration of 50mg/dL of blood alcohol level)
because at this particular level, beyond this it will be
having a significant effect to an individual
→ The symptoms even if it is light, it would automatically
begin at a particular level.
→ .05% (equivalent to a concentration of 50mg/dL of
blood alcohol level) uses currently as basis for the legal
aspects for the drunk driving.
→ The .05% is not what we used in general, this is just
an example for ethanol, there are different specific limit
each where that particular level would cause appearance
of symptoms, so it varies according to the different type
of alcohol
→ Generally, the reaction involving the metabolism of
alcohol would be involving the ff:
✓ Alcohol as catalyzed by the enzyme alcohol
dehydrogenase would undergo oxidation into in
an aldehyde compound so this is general
meaning the aldehyde would be dependent on
what type of alcohol is the primary source. So,
this will further explain how alcohol metabolized
✓ Alcohol to aldehyde and then aldehyde it will
further oxidized into its acid end product or as
the reaction is being catalyzed by the aldehyde
dehydrogenase. The acid end product will also
be dependent on the type of aldehyde based on
the specific source of alcohol
SPECIFIC TYPE OF ALCOHOL
ETHANOL → alcoholic drinks → alcoholic content of
the alcohol drinks
• Most common abused drug: a CNS
depressant
• Most ethanol is converted to acetic acid →
ethanol would be converted into acetaldehyde as
catalyzed by the enzyme alcohol dehydrogenase
and this would be further converted or oxidized
into acetic acid (so this is the acid end product)
as catalyze by the enzyme aldehyde
dehydrogenase (METABOLISM OF ETHANOL)
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→ Aside from acetic acid, its other end product is
ACETYL COENZYME A (COA) → reaction involving the
metabolism of ethanol.
• ETHANOL CAUSES: An increase in GGT, AST,
AST/ALT ratio (more than 2.0), HDL and
MCV- mean cell volume
• SAMPLE USE: Serum, plasma and whole
blood are acceptable specimen (the
venipuncture site should be cleaned with
alcohol-free disinfectant- Benzalkonium
chloride)
→ We may use a sample depending on what we would try
to measure
→ it’s not that sensitive or not that strict in terms of
sample being use. But do remember that it depends on
the test kit we will be using or based on the reference of
that test kit that we will be using.
REMEMBER!!!!
• We are not allowed to use alcohol as the
disinfectant because it is important to use
alcohol free in the blood extraction to avoid
contamination of the sample with the alcohol
present from the ethyl alcohol or isopropyl
alcohol that we would be using for disinfecting
the skin
→ Generally, ethanol causes diuresis because it affects
the production of antidiuretic hormone or the AVP
➢ Ethanol affects the electrolyte balance so, it
disrupt the water balance
o if you notice after drinking alcoholic
drink the tendency is that you go often
to the cr to urinate and that is the
indicator of its diuretic effect
• Causes diuresis by inhibiting ADH
→ Chemical formula of ethanol
→ Generally, what are the things we should remember
about ethanol:
• Induces “Hangover symptoms” → blurred
visions, and headache.
o this hangover symptoms are caused by
the production of acetaldehyde and
further production of the acetic acid
• Specimen: serum, plasma & whole blood
• Major metabolic pathway: Conversion to
acetaldehyde by alcohol dehydrogenase →
ethanol oxidized into acetaldehyde and further
oxidize into acetic acid as catalyzed by the
enzyme alcohol dehydrogenase and acetyl
dehydrogenase
• Methods of testing: Enzymatic, GLC (gas-
liquid chromatography), Osmometry
• Detection limit: 12 hours → could be further
exposure after drinking within 12 hours after the
intake of ethanol
• Fatal dose: 300- 400 mL → the fatal dose is
applicable if you are drinking ethanol in its
purest form the 100% concentrated,
→ Ex. You drink 500 mL of redhorse is
it automatically fatal? – NO, this
alcoholic drink would only be containing
certain percentage, so we have 10% so
the certain proof of alcohol is not 100%
alcohol so its not automatically what we
are drinking. The effects of it are
different in terms of the type of alcohol
according to how high its alcoholic
content is
• Toxic Blood Levels: 250-400 mg/dL → At
this particular level we will be having an
appearance or there is already a presence of the
toxic type of symptoms, meaning there is
already a significant effect to the body, although
at 50 mL there is already an effect, but we don’t
consider it to be toxic already.
→ So, this is the significant volume that we need to see
because further reaching this dosage most of all the fetal
dose as the name itself that is already be fetal to the
patient
THE PATH OF ALCOHOL IN THE BODY
1. Mouth: alcohol enters the body.
→ most common primary exposure would be
through the ingestion or through drinking of the
alcohol. Through the mouth, alcohol would enter
the body.
2. Stomach: some alcohol gets into the
bloodstream in the stomach, but most goes
on to the small intestine.
o Within the different points of the
gastrointestinal tract there would be
absorption which would occur, some
16 | C C 2 L E C 1 4 I N T R O T O T O X I - E T H A N O L
alcohol would get into the bloodstream
through the stomach, but it is very
minimal
3. Small Intestine: alcohol enters the
bloodstream through the walls of the small
intestine.
o majority of alcohol would be absorbed
in the small intestine specifically the
activity of microvilli of the small
intestine
4. Heart: pumps alcohol throughout the body.
o responsible for regulating the activity of
the circulatory system
o responsible for pumping the alcohol
containing blood throughout the body
▪ whether you like it or not a
portion of alcohol would
automatically reach the brain
because alcohol is a small
compound it could readily
cross the placenta
▪ there is a saying that if you
drink alcohol you should put it
in your stomach not in your
brain, which ever amount or
type of alcohol you take a small
portion of it will readily go to
the brain
5. Brain: alcohol reaches the brain.
6. Liver: alcohol is oxidized by the liver at a rate
of about 0.5 oz per hour
o One of the most significant organs every
time you take or every time, we drink
alcoholic drink would be the liver.
o Why is it significant? It is because liver
is the primary one which filtered out the
blood so basically all the contents of the
alcohol that the small intestine
absorbed would first pass (because we
have what we called first pass) so it
would first pass through the liver and
primarily majority of the metabolic
processes would occur and that is why
the first organ to be damage if a patient
is taking too much alcohol or they take
alcohol on a daily basis, so it is chronic
alcoholism already so the first that
would be affected is the liver
→ Acetyl coenzyme A- as a glucose metabolic
pathway it is one of the starting compounds to
produce energy for ATP production, from acetyl
coenzyme A it will now enter the Kreb’s cycle.
Alcohol is just like this, since it has an end
product of acetyl coenzyme A it also causes
production of water carbon dioxide and energy,
but it is not necessary mean that it is a good
source or it can be a good production of energy
remember there is also a significant effect on the
certain level of alcohol so in other words it is the
other product of it except from the acetic acid,
so this is not a significant replacement for
glucose.
ABSORPTION
• ETHANOL Rapidly absorbed from stomach,
small intestine, and colon → primary source on
how alcohol would be entering the blood
circulation
• Maximal blood concentration could be reach
within 30 to 90 minutes
o range at such time which is from the
initial intake this will the starting point
where our different organs will absorb
alcohol and that would be the
o start where significant concentration
would have certain effects on the
different organ. So, you will be having
possible symptoms after such time
• Can be absorbed through the lungs
→ the general or systemic effect and some of the local or
specific effect would be cause by its presence once it
enters the circulatory system
→ Upon reaching the blood circulation and specifically
the lungs, when the alcohol haves a contact present from
the blood in the alveoli cells of the lungs, this alveoli
cells of the lungs would be able to absorb also alcohol,
so remember
• one of the primary characteristics of alcohol in
general is their volatility they are volatile they
will evaporate in air. So, the alcohol molecules
passing through the alveoli would be absorb and
it would be transferred and converted into, or it
would be evaporated, and it would be
transferred out through the body to breath
→ So, the alcohol leaves at an average rate of about
➢ 0.015 g/100 mL/ hr → this is the rate of
clearance.
o In a way this means that our body is
also one of the mechanisms of
elimination although it is not that
significant amount, still it can eliminate
17 | C C 2 L E C 1 4 I N T R O T O T O X I - E T H A N O L
through exhalation so that is also why
one of the method we use for testing for
the present of alcohol would be the use
of breath analyzer, after sometime when
the alcohol is in our blood circulation
automatically a portion of it would be
exhaled through breath so it is easy to
know that the patient has an alcohol
intake.
DISTRIBUTION
→ has no specific organ where it is accumulated
• Uniformly distributed throughout tissues
and body fluids → That is the reason why the
effect is systemic.
→ You’ll become red, or you will be having a
symptoms or it will see in you that you were
intoxicated. Physically you can have a changes
in the appearance of an individual there is a
flushing of the skin, redness, of course there is
an effect inside the body in which it will be
inducing diuresis so you would urinate more and
so on and so forth.
→ Remember!!!!
• Readily crosses placenta, to exposure
fetus → that is why for pregnant mothers who
are still drinking alcohol during the period of
pregnancy or during the conception of growth
and development of the baby in the womb so it
could have a significant effect to the baby, that
is why it is strictly that a pregnant woman is not
allowed to take any alcoholic drink no matter
how small the amount it is, the alcohol content
of it could still cross the placenta.
ELIMINATION
• Urinary, Excretion, Exhalation
→ Primary would be through urinary execration
and a portion of it would be eliminated through
exhalation
GENDER DIFFERENCES
→ In terms of individual differences specifically in terms
of gender there is a difference between male and female
population because of the rate of metabolism the
characteristic metabolism among the different gender
• Females have higher blood alcohol levels
than males → they can take the same volume,
but it is possible that there is a certain
difference in their blood alcohol level because it
varies according to the absorption as well as
metabolism
• Males have higher stomach metabolism of
alcohol than females → so if you notice the
male has a higher tolerance in alcohol compared
to female
EFFECTS ON THE BODY
→ Alcohol has a significant effect on the different organs
in the body.
• Central Nervous System
o Accelerates the loss of brain cells,
contributing to cognitive deficits. →
Significant for developing fetuses and
embryos because alcohol can cause
shrinkage of brain so for the mothers
who continuously drinking alcohol
expect that their child could have
cognitive deficits, not necessarily that
they have mental problem they may be
born as a normal individual but
academically possibly these children
may have low IQ level.
o Chronic use can lead to brain
damage.
→ too much intake of alcohol is not a good practice,
occasional drinking could do but for us as a Filipino
genetically the limit of our body is low compared to the
population of other countries which is drinking alcohol
there is stable, genetically their body has a higher
tolerance compared to us. So, it means that we easily
reach the toxic level, so it has already as significant
effect to those different organs in our body
✓ Example: if we are going to compare Filipinos to
German where they include drinking alcohol for
their everyday lives, so if we compare the
tolerance the German has a high tolerance
compared to Filipinos.
• Liver → have the most significant effect
o Long-term excessive drinking can
cause hepatitis (inflammation and
destruction of liver cells) and
cirrhosis (scarring and shrinkage of
the liver)
o Alcoholism could lead to fatty liver or
may cause toxic hepatitis or
unfortunately it may lead to cirrhosis.
18 | C C 2 L E C 1 4 I N T R O T O T O X I - E T H A N O L
pressure and the one taking
maintenance for diabetes

→ Take note this people who take amlodipine and

So, what would be the difference?
metformin is strictly prohibited in drinking alcohol
→ Fatty liver and hepatitis this are condition in which it especially when they are doing it in a daily basis
still reversible wherein when it is control, manage, and o Alcohol use can also worsen high
treated the liver could still revert back somehow to its blood pressure and diabetes, two
normal function risk factors for heart disease.
→ Cirrhosis which is happen to an individual this would EFFECTS ON LIVER
be involving scarring and shrinkage of the liver so the
hepatocytes are being replaced or it is converted into
fibrous and scar tissues which are no longer functional so
it is already diminished and the function of the liver is
decreasing until such time that it may lead to liver failure

→ The common concern about the effects of the liver is

that sometimes the sign and symptoms is disregarded by
the patient that is why sometimes when they go for
→ This picture shows the characteristics effects of
checkup, and the symptoms is very distinct already
chronic alcoholism in the liver
sometimes they are finding out that the condition is
already cirrhosis. → If it is hepatitis and fatty liver somehow a portion of
the hepatocyte can still be back into its normal function
➢ Due to poor health seeking behavior, hindi agad
but when it is cirrhosis there will be no improvement
naagapan when it is just in the fatty liver or
further or it will not be back to its normal state.
hepatitis
EFFECTS ON KIDNEYS AND BRAIN
→ Alcohol induces or it causes diuresis
• Kidneys
o Impairs their ability to regulate the
volume → it affects the balance; it
affects the electrolyte balance and
composition of fluid and electrolytes
in the body.
o It is very significant for example after Kidney – fatty accumulation, changes in the
drinking alcohol aside from diuresis it structural component/characteristic.
can also have vomiting so make sure to Brain – neonates (mother taking alcohol while
replenish yourself with this electrolyte pregnant
to prevent further electrolyte imbalance
- If there is such exposure on alcohol,
→ This is not a medication for hangover, or it will not there will be very significant effects.
prevent the further effect of alcohol rather electrolytes
would only primarily replace or replenish when the ETHANOL OVERDOSE - excessive
electrolyte present in the body is decreasing. • Stupor/ coma – comatose, loss of
consciousness
➢ the Gatorade is not a medication to hangover it
• Hypothermia /hyperthermia
just for replenishment
• Respiratory depression
• Respiratory acidosis
• Heart
o Chronic, heavy alcohol use
increases the risk of heart disease.
o Mostly the tandem conditions the one
who take maintenance for high blood
19 | C C 2 L E C 1 4 I N T R O T O T O X I - E T H A N O L
ACUTE EFFECTS OF ALCOHOL INTOXICATION – ▪ if it goes beyond 1% and
depends on the amount of alcohol intake, tolerance, above = legal
and metabolism. implications/liability because
it goes beyond the limit (not
- the higher the amount of alcohol in the blood acceptable even for private,
circulation, the more significant/distinct it becomes public vehicles and
• CNS Depressant motorcycle drivers) = even
traces are not acceptable
• Depression of inhibitory control
▪ caught driving a PUV
• Vasodilation, warm, flushed, reddish skin
(public utility vehicle) = has
• Emotional outbursts
no range, caught
• Decreased memory & concentration
automatically, subject to
• Poor judgment investigation for drunk
• Decreased reflexes driving.
• Decreased sexual response
INFLUENCE OF ACUTE ETHANOL INGESTION
LONG TERM ADVERSE EFFECTS – repeated ON ETHANOL LEVELS AND BEHAVIOR
intake of alcohol
- expressed both in conventional and in SI unit.
- Adverse/toxic effects would occur if an individual is
taking roughly 50 g of ethanol per day on a daily OUNCES BLOOD INFLUENCE
basis in a period of about 10 years. = Accumulated CONCENTRATION
effect – amount of alcohol
in the blood
• Obvious 1–2 10–50 mg/dL (2.2– None to mild
o Alcoholism, death, cancer (oral 10.9 mmol/L) or euphoria
cavity, esophagus, liver (progression 0.01 – 0.05%
to cirrhosis)), fetal effects – children 3–4 50–100 mg/dL Mild influence
born to mothers with chronic (10.9–21.7 mmol/L on
alcoholism (FAS) or greater = stereoscopic
statutory limit in the vision and dark
• Alcoholism
Philippines adaptation
o Cirrhosis of liver, appetite loss, poor
3-4 100 mg/dL (21.7 Legally
judgment mmol/L) = varies intoxicated
according to the
• Subtle – not too noticeable, individuals who statutory limit on
are drinking too much on a daily basis for a your country.
long period of time may have: In general, 100 is
o Lost productivity, impaired the upper limit =
performance, motor impairment, cost Beyond 100 -
to society (drunk driving and could significant
cause accidents) symptoms that can
▪ In the Philippines, we have affect activity in
terms of driving.
anti-drunk driving law which
4–6 100–150 mg/dL Euphoria;
states that we have a
(21.7–32.6 mmol/L) disappearance
statutory limit of 0.05% or of inhibition;
50 mg/dL (acceptable) prolonged
▪ The statutory limit varies reaction time
depending because in other - Sobriety test
countries, the limit is 100 for drunk
mg/dL for it to be considered driving = one
as legally intoxicated. of the initial
▪ If not above than 0.05% - tests would be
acceptable because it will to see if you
not impair their capability can follow the
to drive. light/pen of a
police officer. =
those who are
20 | C C 2 L E C 1 4 I N T R O T O T O X I - E T H A N O L
considered to • Increases in
be drunk have AST – aspartate serum activity
slow reaction aminotransferase can occur in
time. many non-
- Could stand ethanol related
on one foot. liver disease
If not • not solely specific
performed, • A ratio of greater
subjected to AST/ ALT ratio – than 2.0 is highly
breath Alanine specific for
analyzer. transaminase ethanol related
6–7 Moderately liver disorder
150–200 mg/dL severe • If it goes beyond
(32.6–43.4 mmol/L) poisoning; 2.0 – considered
reaction time to be
greatly characteristic in
prolonged: loss studies.
of inhibition • Individually, if you
and slight would be looking
disturbances in to their
equilibrium and concentration, it
coordination is increased in
8–9 200–250 mg/dL Severe degree chronic
(43.4–54.3 mmol/L) of disturbances alcoholism, but it
- toxic level of equilibrium is not specific for
and chronic
coordination; alcoholism only
retardation of • High serum HDL
the thought HDL- high density is specific for
processes and lipoprotein ethanol related
clouding of liver disease
consciousness
• Increased
10–15 250–400 mg/dL Deep, possibly erythrocytes MCV
(54.3–86.8 mmol/L) fatal coma is commonly
400 = fatal dose MCV – mean cell seen with
volume excessive
COMMON INDICATORS OF ETHANOL ABUSE/ ethanol
consumption.
LABORATORY RESULT – not immediately seen in
• Increases are
an individual but rather seen in chronic alcoholism
not related to
NOTE: For enzymes, their concentration should not folate or
be directly correlated solely to chronic alcoholism vitamins B12
deficiency
because there are other conditions which may also
• No folate of
be the source of increase of these particular
vitamin B12
compounds/enzymes.
deficiency but
TEST COMMENTS have increased
MCV = possible
GGT – Gamma- • Increases can be
glutamyl transferase reason is due to
seen before the
chronic
→ Marker for chronic onset of
alcoholism
alcoholism pathologic
consequences.
• Increases in
serum activity
can occur in
many non-
ethanol related
condition
21 | C C 2 L E C 1 4 I N T R O T O T O X I - E T H A N O L
FETAL ALCOHOL SYNDROME (FAS) Fetal Alcohol Syndrome (1st pic)

• Most common preventable cause of adverse ➢ low nasal bridge

CNS development – choice of the mother if ➢ minor ear abnormalities
she will take alcoholic drinks during ➢ indistinct philtrum
pregnancy or not. = not sensationalized/ ➢ micrognathia
common in the Philippines ➢ epicanthal folds
• Mothers drinking alcohol while pregnant ➢ short palpebral tissues
o 4,000-12,000 infants per year in US ➢ flat midface and short nose
➢ thin upper lip
CHARACTERISTICS OF FAS
(2nd pic)
• Low birth weight
• small head circumference – shrinkage of ➢ small head
the brain, not the same with normal brain ➢ epicanthal folds
• failure to thrive – can survive to adulthood ➢ flat midface
but still have significant effect ➢ smooth philtrum
• developmental delay – delayed ➢ underdeveloped jaw
communication or motor skills ➢ low nasal bridge
• organ dysfunction – depending on the organ ➢ small eye openings
that have significant effect ➢ short nose
➢ thin upper lip
• facial abnormalities, including smaller eye
openings, flattened cheekbones, and ALCOHOL & CANCER
indistinct philtrum
• epilepsy – prone to epilepsy • Cancer – chronic adverse side effect
• poor coordination/fine motor skills • Ethanol consumption increases risk of
• poor socialization skills, such as difficulty cancer:
building and maintaining friendships and o Oral Cavity
relating to groups o Pharynx and Larynx
• lack of imagination or curiosity o Esophagus
• learning difficulties, including poor memory, o Liver
inability to understand concepts such as time ALCOHOLISM – ALCOHOL DEPENDENCE
and money, poor language comprehension,
poor problem-solving skills Characterized by the following:
• behavioral problems (patay na bata),
including hyperactivity, inability to • Craving: A strong need, or compulsion, to
concentrate, social withdrawal, drink.
stubbornness, impulsiveness, and anxiety – • Loss of control: The inability to limit one’s
common among those babies who were born drinking on any given occasion.
to mothers who are still drinking alcohol • Physical dependence: Withdrawal
during pregnancy. symptoms, such as nausea, sweating,
shakiness, and anxiety, occur when alcohol
EFFECTS OF PRENATAL ALCOHOL use is stopped after a period of heavy
drinking.
• Tolerance: The need to drink greater
amounts of alcohol in order to “get high.”
- It would take large amount of alcohol
before having significant symptoms
• Their idea: they really need alcohol for them
to function properly, if not they will have
withdrawal symptoms.
22 | C C 2 L E C 1 4 I N T R O T O T O X I - E T H A N O L
ALCOHOL WITHDRAWAL EFFECTS - have to
undergo rehabilitation and need professional help
• Tremor
• Nausea
• Irritability
• Agitation
• Tachycardia
• Hypertension
• Seizures
• Hallucinations
DETERMINATION OF ALCOHOL
• Serum, plasma and whole blood specimen
of choice.
• Do not use disinfectant with alcohol, replace
it non-alcohol containing disinfectants such
as benzalkonium chloride.
• Alcohol in blood samples may be analyzed
even after moment of delay provided the
samples in tubes remained sealed.
o Volatility of alcohol – prevent
opening and closing of the specimen
o Evaporation of significant portion of
alcohol.
o The best way to maintain or keep the
sample would be through sealing
the container. Separate a certain
amount needed for the sample, seal
it and keep it. Do not get it from the
primary source that you will use for
other tests because it will be
exposed to air.
• Sealed specimen can be refrigerated or
stored for 14 days without loss of ethanol
at a temperature of 2-8°C.
ENZYMATIC TEST
• Commonly used for enzyme determination
based on the changes of its cofactor.
• Oxidation reduction between NAD
(nicotinamide adenine dinucleotide) and
NADH (nicotinamide adenine dinucleotide
hydrogen) or the reduced NAD = measured
at 340 nm (same with enzyme testing)
• Alcohol dehydrogenase – significant
compound involved.
• Alcohol is measured from blood using
alcohol dehydrogenase as reagent
CHROMATOGRAPHIC METHODS
• Involving measurement of gas.
• Possible methods: It could be GLC or Gas
Chromatography only or Gas
Chromatography in tandem with Mass
Spectrometry.
• GLC (Gas Liquid Chromatography) -
Legally accepted method for ethanol
testing
• For preference, Gas chromatography is
commonly used but the Gas Liquid
Chromatography is the one which is legally
accepted.
o The primary reason is due to its
characteristic of being volatile.
o Presence of gas
BREATH ETHANOL – use of breath analyzer
• growing clinical interest in the determination
of breath alcohol at the point-of-care.
o At the point of contact, you can get
the level of alcohol based on blood
alcohol concentration according to
the amount of the alcohol obtained
from the breath analyzer.
o Correlates with a certain ratio
• fundamental principle: for use of breath
analysis is that ethanol in capillary alveolar
blood rapidly equilibrates with alveolar air
in a ratio of approximately 2100: 1 (blood:
breath).
o For every 2100 parts of alcohol in the
blood, 1 part of alcohol present in the
breath.
o We have a significant amount
excreted through exhalation per mL
of blood per hour.
o Correlate to blood alcohol
concentration.
o Ensure that the attachment is newly
opened (yung kinakabit daw sa
breath analyzer)
o Use different analyzers for several
individuals.
• Before breath analysis, a waiting period of 15
minutes is required to allow for clearance of
any residual alcohol that may have been
present in the mouth (e.g., very recent
drinking, the use of alcohol-containing
mouthwash, or vomiting alcohol-rich gastric
fluid).
• Several commercial evidential breath alcohol
measurement devices are available.
• These devices use:
23 | C C 2 L E C 1 4 I N T R O T O T O X I - E T H A N O L
o (1) infrared absorption
spectrometry (most common) –
commonly used instrument for
breath analyzer
o (2) dichromate-sulfuric acid
oxidation-reduction (photometric
method)
o (3) GC -Gas Chromatography (flame
ionization or thermal conductivity
detection),
o (4) electrochemical oxidation (fuel
cell), or
o (5) metal-oxide semiconductor
sensors
SALIVA ETHANOL
• Non-invasively collected – you may simply
ask the individual to collect saliva in a
container
• Saliva is absorbed onto a swab, which is
then inserted into the test cartridge. Ethanol
measurement is based on an ADH reaction
coupled with a diaphorase-mediated color
indicator reaction, which provides for visual
end-point detection on a thermometer-like
scale after 2-minute incubation
o Strip just like a pregnancy test kit
o It could be in the form of cartridge
device or test strip.
o The reaction is mostly based on the
changes in color due to the presence
of dye or color indicator.
o Qualitative determination of the
presence of alcohol.
• A test card device for the qualitative
measurement of ethanol in saliva or urine is
also based on an ADH-diaphorase- coupled
detection scheme. This test card is designed
to produce a positive response for ethanol
concentrations greater than 0.02 g/dL.
• device consists of a plastic test strip suitable
for insertion under the subject's tongue or
into collected saliva. After saturation of the
reaction pad with saliva and a 2-minute
incubation period, an ADH-diaphorase
coupled indicator color bar becomes visible if
the ethanol concentration is 0.02 g/dL or
greater.
o It could be in the form of cartridge
device or test strip.
2. METHANOL (Wood Alcohol)
• Also known as the “wood alcohol”
• Is a commonly used solvent and contaminant
of homemade liquors.
o Lambanog – most common source
of toxicity of methanol
o A few years ago, there had been
several cases of groups of
individuals who are rushed to the
hospital and there was even a fatality
in which they have had methanol
poisoning because of a poorly
prepared and wrongly produced
lambanog.
o People in this industry should be
made aware if the process is wrong
that could readily result to production
of a toxic compound.
• It is converted first to formaldehyde, then
finally to formic acid by hepatic ALDH.
o Catalyzed by alcohol
dehydrogenase and aldehyde
dehydrogenase respectively.
▪ These byproducts would be
responsible for the toxic
effects = death and
blindness
• Formic Acid -optic neuropathy - blindness
• CHARACTERISTIC: Methanol is rapidly
absorbed from gastric mucosa.
o Signs and symptoms may
immediately appear after the
ingestion of toxic preparation of
alcohol/methanol.
• Fatal dose: 60-250 mL
Symptoms
• Highly more toxic as compared to ethanol
• Vomiting, abdominal pain, visual problems,
blurry vision, blindness, confusion, lethargy,
seizure, comatose, low blood pressure,
death.
Tests
• A history and physical exam will be
performed. An alcohol screen and serum
osmolality can be used to identify the
toxic ingestion. Other tests will be done to
establish the severity of the disorder.
o non-specific and not solely used for
methanol = general test to determine
what may have been the effect of
methanol.
24 | C C 2 L E C 1 4 I N T R O T O T O X I - E T H A N O L
• Standard Workup CBC – to determine the
effects in the formed elements.
• Chem 12 – composed of several routine
tests done in clinical chemistry such as:
profile determination of glucose level,
determination of proteins, etc.
o If tested, you are notsuspected of
having poisoning but rather just to
determine the affected analytes and
biomolecules in the body.
o Can be included as part of a typical
check-up
• X-Ray
METHANOL
Treatment
• The administration of ethanol or preferably
fomepizole to inhibit the metabolism of
methanol in order to further avoid the toxic
effects/adverse effects due to the products of
metabolism.
• Sodium bicarbonate therapy to help
alleviate the metabolic acidosis
• Folate administration to enhance folate-
mediated metabolism of formate (end
product)
o To make the end product of the
metabolism less adverse or less
serious.
• The use of hemodialysis to enhance
clearance of methanol and formate.
o Aside from the capability of the body
to eliminate, it might be taking too
long, the presence of metabolic end
products can have a significant effect
in the body.
o It is better to make the elimination
faster = undergo hemodialysis
3. ISOPROPANOL (Rubbing Alcohol)
• Rubbing alcohol
• Isopropyl alcohol – readily available in the
market
• It is a colorless, flammable chemical
compound with a strong odor. - additive
• It is the simplest example of a secondary
alcohol
• It is metabolized to hepatic ADH to acetone
• Production of acetone = end product of
metabolism of isopropanol
• Fatal dose: 250 ml chemical compound -
pertaining to pure or 100% isopropyl alcohol.
o Fatality would typically occur if you
would have direct exposure to 100%
or concentrated isopropanol which
would readily enter blood circulation.
o If only applied to skin – not fatal
o It will only become fatal if (e.g., self-
made alcoholic drink made with
isopropyl alcohol) = possible to
cause toxicity
• Isopropyl alcohol is oxidized by the liver
into acetone by alcohol dehydrogenase.
• Symptoms of isopropyl alcohol poisoning
include:
o Flushing
o Headache
o Dizziness
o CNS depression
o Nausea
o Vomiting
o coma.
• Poisoning can occur from (possible
routes of exposure): ingestion, inhalation,
or absorption; therefore, well-ventilated areas
and protective gloves are recommended.
o Ingestion – most potent exposure
(e.g., drinking isopropyl alcohol from
the market if they are deprived of
alcoholic drinks)
o Inhalation – exposed to steam of
water that have alcohol content (e.g.,
if you would be doing bed bath on
bedridden individuals and you would
be doing it frequently, it is better to
use ethyl alcohol)
▪ Ethyl alcohol is preferred to
use as disinfectant as
compared to isopropyl.
o Histopath section – do not enclose
yourself when doing dilution of
alcohol. Ensure that it is well-
ventilated. In histopath, you would be
25 | C C 2 L E C 1 4 I N T R O T O T O X I - E T H A N O L
using several chemicals which are
harmful for the body. (e.g., xylene)
▪ Minimize exposure by
ensuring that the laboratory
is properly set-up and well-
ventilated.
4. ETHYLENE GLYCOL (1,2 ethanediol)
• It is a common constituent of hydraulic fluid
antifreeze.
• Known as an active composition or
constituent of the anti-freeze
• Considered as one of the significant
alcohols in terms of toxicity or poisoning
since there have been several cases before
of antifreeze poisoning.
• Ingestion by children is common because
of its sweet taste.
• Neon green is usually the color =
modification
• It is converted to oxalic and glycolic acid
• Production of final products leads to
deposition of calcium oxalate crystals in
renal tubules.
o In the urine sample of an individual
with ethylene glycol poisoning – you
would see calcium oxalate crystals or
the diamond shaped crystals.
• Specimen collection: used an alcohol-free
disinfectant.
• Fatal dose: 100 grams of antifreeze
B. CARBON MONOXIDE
• It is a colorless, odorless, tasteless gas, very
toxic substance.
• It is of great clinical significance because
there have been several cases of carbon
monoxide poisoning and formula cannot be
changed to make it identifiable.
• Common causes of carbon monoxide
poisoning:
o exposure to the exhaust of cars
because carbon monoxide is a
product of the combustion of carbon-
containing substances.
o People found dead in the garage of
their homes simply because of
carbon monoxide poisoning because
no proper air circulation without them
knowing that they are already
exposed.
o Some of the cases of poisoning
happens while an individual is
sleeping (sleeping in cars, enclosed
parking spaces) = readily causes
death
• Rapidly absorbed into blood from inspired air.
• Produced by incomplete combustion of
carbon –containing substances. (Such as
petroleum products)
• Toxic effects are manifested by binding with
divalent iron with heme protein
(cytochromes, myoglobin and
hemoglobin)
o Hemoglobin (which would be
carrying oxygen) – converted to a
carboxyhemoglobin which is doesn’t
have the same normal characteristic
of normal hemoglobin carrying
oxygen. = no exchanges in the
cells and lungs as well as the
different tissues in the body.
o Carboxyhemoglobin – stays within
the blood circulation hemoglobin is
unable to further carry oxygen –
diminishes oxygen carrying capacity
which would also result to inability of
your hemoglobin to deliver sufficient
amount of oxygen towards the
different cells and organs of the
body.
• The only treatment for carbon monoxide
poisoning is:
o 100% oxygen therapy
• It inhibits cellular respiration and electron
transport. (effects)
o Eventually, this may also lead to
acidosis and cell death.
o Lethal/fatal effect to the victim or
patient
• Source of plastic fire: gasoline engines,
wood
o Emits exhaust caused by combustion
of oxygen such as fires such as
plastic fires, gasoline.
o Exhaust of cars contains significant
amounts of carbon monoxide.
• Effect: hypoxia
• Indicator of toxicity: cherry red color of the
face
o Close to arterial blood appearance
o Not because of oxygen but because
of carboxyhemoglobin
• Aspiration is usually associated with
pulmonary edema and shock--- death.
o Inhalation – most common route of
exposure since it is a gas.
26 | C C 2 L E C 1 4 I N T R O T O T O X I - E T H A N O L
SYMPTOMS OF CARBOXYHEMOGLOBINEMIA → 60-70% there would already be possibility on
unconsciousness, respiratory failure, and eventually
→ depending on the level of carboxyhemoglobin in the
death
blood circulation
→ At 80% carboxyhemoglobinemia is already considered
COHB (%) SYMPTOMS AND to be fatal because there would be no distribution of
COMMENTS
oxygen in the different organs of the body so of course
0.5 Typical in nonsmokers
oxygen is needed by the cell for it to function properly, so
5-15 Range of values seen in
if there is no oxygen source this may eventually lead to
smokers
10 Shortness of breath with death.
vigorous exercise CARBON MONOXIDE SIGNS & SYMPTOMS
20 Shortness of breath with
moderate exercise • Flu-like symptoms (without fever or runny
• Significant level nose) including:
30 Severe headaches, fatigue, o Headache
impairment of judgement o Fatigue/sleepiness
40-50 Confusion, fainting on o Shortness of breath
exertion o Nausea
60-70 Unconsciousness, o Dizziness
respiratory failure, death o Confusion or disorientation
with continuous exposure → if you see these symptoms in a group
80 Immediately fetal of individuals whose working in an
→ We are not totally free from carbon monoxide, since it enclosed garage then please have them
is typically seen in the air because it is the product of check because that may be carbon
combustion of gasolin it is expected that we do have it in monoxide poisoning
our blood circulation but in a small amount only, • SUSCEPTIBLE GROUP:
o Young children
→ Roughly about 0.5% for nonsmokers,
o Elderly
→ Roughly about 5-15 because it mostly bind to a target o household pets are usually affected
cell tissue or target cell compound for those who are first
smokers so they have a higher percentage. → especially if they do not have a capability in
going away from that situation, that’s why they
• As the level of percentage goes up then there are the most potent
would be a significant effect on the individual. → It is very crucial, so we shouldn’t leave our
children inside the car even if the aircon is on
→ 10%, patient may be experiencing shortness of breath
they are still prone to carbon monoxide
but during with vigorous exercise because it means that
poisoning especially if you have in a parking
the gas exchange is not that efficient, or the oxygen
space inside a building which is close, take note
distribution is not that efficient already.
that the aircon has a setting in which it has an
→ At 20% there is a shortness but not necessarily access outside so the carbon monoxide is still
vigorous even moderate exercise, or not so difficult going inside the car
exercise it may cause already a shortness of breath and → If you want to sleep inside a car at least you
take note at 20% we already consider it as significant are park in a place where there is a good
level. ventilation you can still sleep with the aircon but
still you should leave a small space on the
→ Going above at 30% this may already cause severe window for somehow hindi lang naiipon sa loob
headache, fatigue, impairment of judgement ng car yung carbon monoxide
→ The 20 and above is considered already as toxic
already

→ At 40-50% there would be confusion, fainting on

exertion because the skeletal muscle and cardiac muscle
would be deprived of oxygen
27 | C C 2 L E C 1 4 I N T R O T O T O X I - E T H A N O L
CARBON MONOXIDE
→ For a non-gas carbon monoxide, it may also cause
toxicity due to ingestion so this may target the GIT.
→ In terms for the common exposure, our most common
is coming from the air so inhalation, but there are also
several cases of poisoning due to ingestion and if it is
ingestion then the primary target or be affected is the
GIT, it causes GIT perforation and if there is such this
may be eventually led to a hematemesis, abdominal pain,
and possibly shock
• Ingestion produces lesion in the esophagus
and gastrointestinal tract, which may produce
perforations.
• This result in hematemesis, abdominal pain
and possibly shock.
TEST FOR CARBON MONOXIDE POISONING
→ The blood has a distinct color, it’s look like the arterial
blood but also it is cherry-red
→ What you could do is to perform a spot test, meaning
you will be going to mix the blood with sodium hydroxide
• COHb has a cherry-red appearance. This is
the basis of a spot test for excessive carbon
monoxide exposure.
o 5 mL of 40% NaOH is added to 5 mL
of aqueous dilution (aqueous water
is the diluent) of whole blood.
o Persistence of a pink solution is
consistent with a COHb level of 20%
or greater. → meaning the blood is
mostly composed of carboxyhemoglobin
Two primary quantitative assays for COHb.
→ For quantitative or specific analysis of
carboxyhemoglobin
• perform or do spectrophotometry and gas
chromatography which is considered to be
primary or more precise as well as reference
method.
→ So, for the different toxic agent, majority of them the
preferred methodology is the chromatographic method
• Spectrophotometry
• GC = is accurate and precise and the
reference method for the determination of
COHb.
C. CYANIDE
• It can exist / form as a solid, gas or in
solution → depending on the formulation, but
all this form is considered to be toxic except for
nontoxic form- the thiocyanate, but generally
cyanide is toxic in its purest form
• super toxic substance
→ It is a fast-reacting toxin, this could readily cause
death within an hour after exposure, that’s why it is
called as super toxic substance
• It is a component of insecticides and
rodenticides
→ AVAILABILITY - cyanide is an active composition of
pesticide and insecticide
• Common suicide agent → used before as a
common suicide agent, also in killing multiple
large number of individuals such as those in
concentration camps during the 1940s prior to
the world war and WW2
• It is a pyrolysis agent – burning of plastics
o so the effect of this is just like the
carbon monoxide, it also has an affinity
to the heme molecule that’s the reason
why it causes cyanohemoglobin
• It expresses its toxicity by binding to heme
iron depletion of cellular ATP → in terms of its
toxicity, the major effect of this is since its affect
the hemoglobin, it is also affecting the electron
transport and cellular respiration.
o May eventually lead to cell death
CHARACTERISTICS AND METHOD OF
DETERMINATION
• It has characteristics odor of bitter almonds
→ You will notice in a patient with cyanide poisoning is
that their breath would be having a characteristic odor of
bitter almond
• Exposure can occur by inhalation,
ingestion, or transdermal absorption. →
depending on the form of cyanide, where the
patient exposed if it is gas then its inhalation,
then the liquid and solid would be through
ingestion or transdermal
• METHODS: ion specific electrode
methods (For cyanide) and photometric
analysis → such as the use of chemical
methods or enzymatic method, but usually its
more on the chemical methods for the direct
28 | C C 2 L E C 1 4 I N T R O T O T O X I - E T H A N O L
determination of cyanide content to determine
using spectrophotometrically
• small quantity—typically 200 mg—of solid
cyanide or cyanide solution, and airborne
exposure of 270 ppm may lead rapidly
(within minutes) can readily result to death
o it is usually use before on either
accidental poisoning or through suicide
• Nontoxic product: thiocyanate
→ cyanide- is a common composition of a household
pesticide or insecticide so there is an easy access for
those who will use this for poisoning
→ Characteristically: if you noticed, there is a pink
mauve discoloration when the cyanide is the cause of
poisoning because of the presence of cyanohemoglobin
in the blood circulation
D. CAUSTIC AGENTS
→ Those use to clean sink, muriatic acid, and bleach use
in the laboratory, those are classified as under caustic
agent
• From household products and occupational
settings
• Aspiration – associated with pulmonary
edema and shock → it may affect the lungs
→ if you are for example cleaning in the kitchen, you
shouldn’t mix chemicals basta basta because it may
create fumes which may also be hazardous for your
health
• Ingestion – lesion in the esophagus and GIT
→ perforations → COMMON, its either
accidental or suicide. Ingestion could
immediately cause lesion to the esophagus and
gastrointestinal tract, so mostly in those caustic
agent we don’t want to induce more further
vomiting to the patient because the one they
take will go again to the GIT and esophagus so
better give them compound which somehow will
decrease their metabolism and for further
elimination or to help them eliminate those
caustic agent BUT for those who accidentally
ingested large or concentrated caustic agent,
they would have a long lasting adverse effect
such as there is already a perforation in the
esophagus, may be the cells lining of the
esophagus, stomach lining, and the other part of
the GIT is already been damaged.
→ If it is acquired or the exposure is through ingestion,
this would readily cause vomiting of blood, it may cause
abdominal pain, and a shock to the patient
o Results to hematemesis, abdominal
pain and shock
o Onset of metabolic
acidosis/alkalosis occurs rapidly
→ because readily it would enter in the
blood circulation and therefore affecting
the pH of the blood resulting to
variation in the pH, it varies depending
on the type of caustic agent
• Corrective Therapy- dilution
→ There are some home aids, yung mga binibigyan ng
egg or sa dogs binibigyan ng sugar
→ DO NOT FORCE VOMITING if the patient is not vomiting
in the first place, because it may worsen the situation.
Better one of the first aid given to those who ingested
watusi, or nasubo yung kamay which is soak to those
powder use in fireworks, DOH says that for first aid give
them a certain amount of egg, the egg would avoid
further absorption para hindi na sya makuha ng body
natin and para hindi na sya mapunta sa blood circulation
this is just a first aid but you still need to go to a hospital
to ensure that those compounds is clear already in the
body and to determine what is the significant effect of
this compound to the different organs, because physically
we don’t see any problem but inside, the stomach and
GIT has already been perforated
→ There are groups which are alkaline in nature and acid
that is why if you notice the possible toxic symptoms
either it can cause alkalosis and acidosis, this varies
depending on the type of caustic agent where you are
exposed to
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TYPE EXAMPLES antifreeze) - Metab to oxalic acid glycolic acid
Alkali Sodium hydroxide, Ethanol-like effects, severe metabolic acidosis, renal
potassium hydroxide, tubular damage
(oven cleaners, liquid
agents, liquid drain Carbon Monoxide - Produced by incomplete
cleaners, disk batteries), combustion of carbon-containing substances
calcium and lithium - Primary environmental sources: gasoline engines,
hydroxide (hair relaxers), improperly vented furnaces, & wood or plastic fires
dishwater detergents - A colorless, odorless, tasteless gas rapidly
Acid Sulfuric acid, hydrochloric absorbed into blood from inspired air
acid, nitric acid, (toilet - Considered highly toxic due to its affinity for &
bowl cleaners, swimming binding to hemoglobin
pool cleaners, rust - Decreases amount of oxygen to tissue, producing
removers) hypoxia
Bleaches and other Hypochlorous acid - Tests: differential spectrophotometry & gas
causes (bleach-generally neutral chromatography
pH commercially),
peroxide (mildew Cyanide - Found in industrial processes, insecticides,
remover) rodenticides; produced by burning of some plastics;
common suicide agent
QUESTIONS: - Expresses toxicity by binding to heme iron
- Causes headaches, dizziness, respiratory
Factors affecting absorption (exposure to toxins) depression, leading to seizure, coma, & death
- pH, rate of dissolution, gastric motility, resistance to
degradation in GI tract Metal and Metalloids – Arsenic – Cadmium – Lead –
Dose-Response Relationship - Comparison of Mercury
responses of a therapeutic drug over a range of Cadmium - toxicity primarily by binding to proteins
doses
Organophosphates & Carbamates - function by
ED50 - the dose of drug in which 50% of treated inhibition of acetylcholinesterase, an enzyme
individuals will experience benefit present in both insects and mammals.
TD50 - the dose of drug in which 50% of individuals Acetylcholinesterase - is a neurotransmitter found in
will experience toxic adverse effects both central & peripheral nerves. It is also
LD50 - the dose of drug in which 50% of individuals responsible for the stimulation of muscle cells and
will result in mortality several endocrine/exocrine gland

therapeutic index - the ratio of the TD50 (or LD50)
to the ED50. Drugs with a large therapeutic index
have few toxic adverse effects when the dose of the
drug is in the therapeutic range.
Alcohol - Specific toxic effects:
- Methanol (a common solvent) -Metab to
formaldehyde. Can cause severe acidosis, leading to
death; blindness
- Isopropanol (rubbing alcohol) -Metab to acetone.
Can cause severe acute-phase ethanol-like
symptoms
- Ethylene glycol (component of hydraulic fluid &
Salicylates - Aspirin (acetylsalicylic acid) is a common
analgesic, antipyretic, & anti-inflammatory drug.
Function: decreases thromboxane & prostaglandin
formation through inhibition of cyclooxygenase
Toxic effects (when ingested at high doses)
- Metabolic acidosis, possibly leading to death
- Hyperventilation, respiratory alkalosis, acid-base
disturbance
- Inhibition of Krebs cycle, resulting in excess
conversion of pyruvate to lactate
- Excess ketone body formation
30 | C C 2 L E C 1 4 I N T R O T O T O X I - E T H A N O L
Assays: GC, LC, IA and spectrophotometric (Trinder

Acetaminophen - A commonly used analgesic drug

Amphetamines - Therapeutic drugs used for
narcolepsy & attention deficit disorder

Anabolic Steroids - Group of compounds related

chemically to male sex hormone testosterone.
Increase muscle mass & can improve athletic
performance

Cannabinoids - Group of psychoactive compounds

found in marijuana

Mechanistic - cellular & biochemical effects of toxins

Descriptive - uses results of animal experiments to

predict what level of exposure will cause harm in
humans

Forensic - medicolegal consequences of toxin

exposure

Clinical - interrelationships between toxin exposure

& disease

Exposure to toxins- 50% of poisoning cases are

intentional suicide attempts. 30% of cases are from
accidental exposure. Remainder are a result of
homicide or occupational exposure.

Analytic Methods - Immunoassays (screening), thin-

layer chromatography, gas chromatography, MASS
SPECTROMETRY

ethanol - General toxic effects: disorientation,

confusion, euphoria; progressing to
unconsciousness, paralysis, & even death Specific
toxic effects. Results in diminution of judgment &
motor performance. Chronic consumption leads to
alcoholic hepatitis, cirrhosis.

Xenobiotics- exogenous agents that may have

adverse effects on a living organism. Environmental
chemicals or drug exposures

eg: antibiotics, antidepressants

Poisons - have an adverse effect on biological

system. Animal, plant, mineral, or gas poisons

eg: venom from poisonous snakes, poison hemlock,

arsenic, or carbon monoxide poisonings

Toxins- substances that are biologically synthesized

in living cells or microorganisms. Botulinum toxin
produced from the microorganism, Clostridium
botulinum, hemotoxins produced from venomous
snakes, and mycotoxins produced from fungus