TOXICOLOGY

CLINICAL CHEMISTRY III LECTURE

Aquino, Paula Caryl

Delos Reyes, Czarina
Manio, Chrysler
Ocampo, Charlotte
Sarmiento, Maan
 Toxicology
• A science that deals with poisons and
their effect and with the problems
involved
• The study of the adverse effects of
xenobiotics in humans
 Terms

• Xenobiotics – exogenous agents

that have an adverse effect on a
living organism.
 Terms

• Poisons - also are agents that have an

adverse effect on a biological system, but
more often used when describing animal,
plant, mineral or gas poisons
 Terms

• Toxins – substances that are biologically

synthesized either in living cells or
microorganisms
 Major Discipline
• Mechanistic toxicology - study of physiological,
biochemical and molecular mechanisms by which
toxic effects occur
• Descriptive toxicology - focuses on toxicity
testing of chemicals or agents of toxicity, usually
on animals and then correlated to human
conditions
• Regulatory toxicology - is the branch of
toxicology that uses scientific knowledge to
develop regulations and other strategies for
reducing and controlling exposure to dangerous
chemicals.
 Specialties in Toxicology

• Forensic toxicology
•medical-legal aspects of poisonings
•primarily concerned with medicolegal
consequences of exposure to chemical or
drugs
 Specialties in Toxicology

• Environmental toxicology
• evaluation of environmental chemical
pollutants and their impact on human
health
 Specialties in Toxicology

• Clinical toxicology
• Is the study of interrelationships
between xenobiotics and disease states.
This area emphasizes not only
diagnostic testing but also therapeutic
intervention.
 Three basic exposure pathways

•Inhalation
•Ingestion
•Skin contact
 Other routes
• Intravenous (IV)
• Intraperitoneal (IP)
• Subcutaneous (SC)
• Intramuscular (IM)
• Intradermal
• Occupational Exposures
• Accidental / Suicide Exposures
 Purpose of toxicology testing

• To confirm clinical suspicions of poisoning

• To support investigations of known exposure (spill,
suicide attempts, and fire)
• To comply with occupational regulations or guidelines
 Specimen

• performed with blood or urine

 Specimen considerations

• in order to select the best/appropriate specimen

for a selected test, it is important to recognize
that toxic agents exhibit unique absorption,
distribution, metabolism and elimination kinetics
(toxicokinetics)
• preanalytical variables such as elimination
patterns, analyte stability and specimen collection
procedures
• specimen collection, handling and storage - to
avoid introducing external contamination
 Analytical Method

• Screening test - rapid, simple, qualitative

procedure intended to detect specific substances
or classes of toxicants ; good analytic sensitivity
but lack specificity
• Confirmatory test - are the tests required to
confirm the analysis
 Analytical Method

A.Immunoassays
- are chemical tests used to detect or quantify a
specific substance, the analyte, in a blood or body
fluid sample, using an immunological reaction.
 Analytical Method

B.Thin-Layer Chromatography
- - simple, inexpensive method of detecting
various drugs and other organic compounds
 Analytical Method

C. Gas Chromatography
- - well-established technique for the
qualitative and quantitative determination
of many volatile substances. reference
method for the quantitative identification
of most organic compounds (GC-MS)
 Analytical Method

D.Inductively Coupled Plasma-Mass

Spectrometry / Atomic Absorption
- used for quantitative analysis of
inorganic compounds
 Commonly encountered nondrug
toxins in the clinical setting

• Alcohol
• Carbon monoxide
• Caustic agents
• Cyanide
• Metals and Metalloids
 Alcohol

• a psychoactive substance
• Common CNS depressant
• Initial exposure causes disorientation,
confusion and euphoria then progress to
unconsciousness, paralysis or even death
 Alcohol
Metabolism pathway
hepatic conversion of alcohol to an aldehyde by
alcohol dehydrogenase (ADH), and further
conversion to an acid by hepatic aldehyde
dehydrogenase (ALDH)

ADH ALDH

ALCOHOL ALDEHYDE ACID

 Ethanol

• Chemical name of alcohol

• Most common abused drug
• Causes diuresis by inhibiting ADH
• active ingredient in drinks such as beer, wine, and
distilled spirits
 Ethanol
Metabolism pathway
• Hepatic metabolism
• Final product: acetic acid

ETHANOL ACETALDEHYDE ACETATE ACETALDEHYDE

ADDUCTS
 Methanol

• common solvent
• It may be ingested accidentally as a component of
many commercial products or as a contaminant of
homemade liquors
 Methanol
Metabolism pathway
Initially metabolized by hepatic ADH to the intermediate
formaldehyde. Formaldehyde is rapidly converted to
formic acid by hepatic ALDH

ADH ALDH

METHANOL FORMALDEHYDE FORMIC ACID

 Isopropanol
• Rubbing alcohol
• Metabolized by hepatic ADH to acetone
(metabolic end product)
• Has CNS depressant effects
• Symptoms of intoxication: CNS depression and
hypertension
 Ethylene glycol (1, 2 ethanediol)

•Common component of
hydraulic fluid and antifreeze
•Has sweet taste
 Determination of Alcohol
• Analytical Method: Serum Ethanol
Determination
A. Enzymatic- Enzyme used is a nonhuman
form of ADH which oxidizes ethanol to
acetaldehyde with reduction of NADH. The
NADH produced can be monitored directly
by absorbance at 340nm.
B. Gas Chromatography - Reference method
for ethanol determination. This method can
simultaneously quantitate other alcohols,
such as methanol and isopropanol.
 CARBON MONOXIDE
• Produced by incomplete combustion of carbon containing
substances (Gasoline, Improperly Ventilated Furnacles,
Wood or Platic Fires)
• odorless and tasteless gas that is rapidly abdorbed into
blood from inspired air.
• Carboxyhemoglobin (COHb): When carbon binds to
hemoglobin.
 CARBON MONOXIDE

• Analytical Method
A. Spot test- 5mL of 40% of NaOH + 5mL Aqueous
solution of whole blood, persistence of pink solution
(COHb Level of 20% or Greater)
B. QC: Reference Method of Determination
C. Spectrophotometry- Works on the principal that
different forms of Hemoglobin present with different
spectral absorbancy curves.
D. Cooximetry (Carboxyhemoglobin measurements)
 CYANIDE

• can exist as a solid gas or in solution

• it is super toxic substance widely used in industrial
processes (Insecticides/Rodenticides)
• common suicidal agent
• exposure: Inhalation, Ingestion, transdermal
absorption
 CYANIDE
• indication of toxicity: odor of bitter
almonds breath and altered mental
status.
• antidote: Sodium thiosulfate, amyl and
sodium nitrite
 METALS
• all metals can be toxic if ingested in large quantities and
absorbed in their ionized forms
 ARSENIC

• is a component of ant poisons, rodenticides,

paints and metal alloys. It is a common homicide
or suicide agent
• toxic forms: sodium arsenate, carbarsone,
tryparsamide and arsine gas (most toxic)
 CADMIUM

• Commonly encountered during mining and

processing of many metals
• Found in plants plastics and cathodal material of
nickel-cadmium batteries
• As environmental pollutants-accumulate on
tobacco leaves (smokers)
• Non smokers: consumption of shell fish, meat,
lettuce, and grains
 CADMIUM

• Toxic renal indicator: (+) GGT in urine sample

• Toxicity : Binding to protein, high tendency to
accumulate in the kidney (renal tubular
dysfunction ).
 LEAD

• common constituents of household paints, lead pipes,

gasoline (air borne lead and leaded dust)
• Exposure: ingestion of contaminated of dietary
accounts for most exposure or inhalation
 LEAD
• Evaluation:
• Chromogenic reaction and anodic stripping voltametry (lack
analytic sensitivity)
• AAS – to confirm blood lead levels
• Quantitative ICP - MS
 Mercury

• Metal that exist in 3 forms: Elemental (Liquid at room temp),

Inorganic salts and as a component of organic compunds
• Exposure Inhalation and ingestion, consumption of contaminated
foods as the major source of contamination
• Toxicity, Mercury binding to protein which results in change of
structure and function
 Pesticides
• Substances that have been intentionally added to the
environment to kill or harm an undesirable life from
(insecticides/herbicides)
• Exposure: contamination of food, inhalation,
transdermal absorption and ingestion from hand to
mouth contact
• Toxicity: Inhibition of Acetyl cholinesterase
THANK YOU!