10/14/2022
Introduction
Toxicology: Study of adverse effects of xenobiotics on
the body (Xenobiotics—chemicals and drugs not
Toxicology: Intro normally found or produced in the body)
Clinical Chemistry Review Approximately 24 toxins/drugs account for 80% of
emergency department visits
Useful clinical information:
◦ Time & date of exposure, time & date of specimen,
history and current medical condition
Exposure statistics:
◦ 50% of poisoning cases are intentional suicide attempts.
◦ 30% of cases are from accidental exposure.
◦ Remainder are a result of homicide or occupational
exposure.
Toxicology Definitions
Major disciplines within toxicology: Xenobiotics—exogenous agents that may have
◦ Mechanistic: cellular and biochemical effects of toxins—
adverse effects on a living organism; often used to
describe environmental chemicals or drug
context of a dose–response relationship exposures.
◦ Descriptive: uses results of animal experiments to predict Poisons—also have an adverse effect on biological
what level of exposure will cause harm in humans—risk system; terminology used when describing animal,
assessment plant, mineral, or gas poisons.
◦ Regulatory: used data from mechanistic and descriptive Toxins—substances that are biologically
to establish standards regarding acceptable levels of synthesized in living cells or microorganisms.
exposure—oversees human safety issues associated with Toxidromes: the specific toxic syndrome created
therapeutic drugs, cosmetics, and food additives by a drug
Routes of Exposure Routes of Exposure
Most common: ingestion, inhalation, and Chemical state and exposure route influences
transdermal absorption. toxicity
◦ Ingestion is most often observed in the clinical setting. Skin: fat-soluble chemicals
Toxins are absorbed by processes intended for GI tract: if ingested, it can be absorbed
dietary nutrients or passive diffusion.
Lungs: inhaled – damages mucosa
◦ Diffusion requires that the substance be able to cross the
cellular barriers of the gastrointestinal tract. ◦ Fastest route
Factors affecting absorption: pH, rate of Injections: drugs of abuse
dissolution, gastric motility, resistance to Eyes: chemical splash/gas
degradation in GI tract.
1
10/14/2022
Dose–Response Relationship Dose–Response Relationship
Several systems have been established to index Dose–response curve
relative toxicity of substances to allow ◦ Set for each chemical/drug
assessment of their potential to harm. ◦ The dose–response curve is a comparison of
Most systems correlate dose of a toxin with responses over a range of doses.
harmful responses ◦ TD50 is the dose at which 50% of the population will
experience toxic adverse effects;
More in-depth approach: evaluating data from
◦ LD50 is the dose at which 50% of the population will
a cumulative frequency histogram of toxic
experience a lethal dose.
responses over a range of doses.
◦ ED50 is the dose at which 50% of the population will
experience a therapeutic benefit (effective dose)
Dose–Response Relationship
Individual dose–response relationship: accounts for
individual’s health and as well as exposure levels
Quantal dose–response relationship: describes the
changes in health effects of a population based
on changes of exposure to the xenobiotic
Poisons: no well-defined safe level
Bioaccumulation of some chemicals
◦ No dose-response curve
◦ Endocrine disruptors, example BPA
Dose–Response Relationship Acute and Chronic Toxicity
NOAEL is the highest dosage level at which after chronic Acute toxicity occurs in a short amount of time
exposure of a substance (material) shows no adverse
effects (toxicity) to the tested animals ◦ Single or multiple exposures in a short amount of time
LOAEL: is the lowest dosage level at which chronic (<24hr)
exposure to the substance shows adverse effects on
tested animals ◦ Adverse effects occur within 14 days
NOEL the highest dose or exposure level of a substance Chronic toxicity occurs over longer period of
or material that produces no noticeable (observable)
toxic effect on tested animals time
LOEL: lowest observable effect level (difference ◦ Repeated, frequent exposure for extended periods
between the treated and control group) or continuous exposure
NOELs and LOELs do not necessarily imply toxic or
harmful effects and may be used to describe beneficial
effects of chemicals as well.
