Unit 2 – Introduction to Toxicology
This Unit will provide you with an introduction to occupational toxicology. We will review toxicological
principles including; toxicity, routes of exposure to biological and chemical agents, dose-response
relationships, exposure limits.
By the end of Unit 2, the student will be able to:
• Examine the classes of workplace stresses and hazards
• Understand the study of Toxicology and how we can use it to evaluate the health effects of hazards
in the workplace
• Identify factors that determine toxicity including route of exposure, duration, frequency, and natural
subject variability
• Examine the physical forms of contaminants
• Differentiate between routes of entry
• Examine human anatomy as it relates to metabolism and elimination of chemical contaminants
• Understand dose-response curves, models of toxicity, and exposure limits (TLVs)
In addition to the lesson notes please review the videos and supplementary material posted on the OWL
Lesson.
Toxic Agents
This course will specifically examine the effect that chemical, biological, and physical agents have on the
human body and how we can use toxicology principles to evaluate the health effects of these hazards so
we can assess the risk and implement controls to protect workers.
A toxic agent is anything that can produce an adverse biological effect.
Toxicity is the ability of a substance to produce an unwanted effect when the chemical has reached a
sufficient concentration at a certain site in the body.
Additional hazard classes that are covered in other course include workplace accidents, slips, trips, falls,
electrical or mechanical injuries and ergonomic hazards (repetitive strain and musculoskeletal injuries).
What is toxicology?
Toxicology is traditionally defined as “the science of poisons”. Over time, our understanding of how various
agents can cause harm to humans and other organisms has increased, resulting in a more descriptive
definition of toxicology as “the study of the adverse effects of chemical, physical or biological agents on
living organisms and the ecosystem, including the prevention and amelioration of such adverse effects.”
These adverse effects can take many forms, ranging from immediate death to subtle changes not
appreciated until months or years later. They may occur at various levels within the body, such as an organ,
a type of cell, or a specific biochemical. Our understanding of how toxic agents damage the body has
progressed along with medical knowledge. We no know- that various observable changes in anatomic or
bodily functions actually result from previously unrecognized changes in specific biochemicals in the body.
Some refer to toxicology as the “Science of Safety” because as a field it has evolved from a science
focused on studying poisons and adverse effects of chemical exposures, to a science devoted to studying
safety.
Toxicology uses the power of science to predict what, and how chemicals may cause harm and then shares
that information to protect public health. When talking about toxicology it is important to keep a few things
in mind.
• Not everyone will respond to substances in exactly the same way. Many factors, including the
amount and duration of exposure, an individual’s susceptibility to a substance, and a person's age,
all impact whether a person will develop a disease or not.
• There are times in a person's life when he or she may be more susceptible to chemicals. These
times may include periods of active cell differentiation and growth in the womb and early
childhood, as well as during adolescence when the brain is continuing to develop.
• Just because someone is exposed to a harmful substance does not always mean they will get sick
from it.
• The dose of the chemical or substance a person is exposed to is another important factor in
toxicology. All substances have the potential to be toxic if given to humans and other living
organisms in certain conditions and at certain doses or levels. For example, one or two aspirins
may be good for you, but taking a bottle of aspirin may be harmful.
• Toxicologists also realize that even low-dose exposure is continuous or happens during a critical
window of development.
□ Watch - Toxicology
Remedy or Poison?
Xenobiotic is the general term that is used for a foreign substance taken into the body. It is derived from the
Greek term Xeno which means “foreigner”. Xenobiotics may produce beneficial effects (such as
pharmaceuticals) or they may be toxic (such as lead).
□ Watch - Xenobiotics
As Paracelsus proposed centuries ago, dose differentiates whether a substance will be a remedy or a
poison. A xenobiotic in small amounts may be nontoxic and even beneficial, but when the dose is
increased, toxic and lethal effects may result.
Let’s look at these common fruits and vegetables. They contain very small quantities of potentially harmful
natural chemicals, but you don’t see people avoiding eating these regularly.
Just because a chemical is present, does not mean that it is harmful in the dose present. Let’s take a closer
look at a more harmful misconception. This image illustrates the amount of formaldehyde in a pear
compared to vaccines.
Note that vaccines contain less than 1% of what naturally occurs in a pear. Unfortunately, when you’re not
properly informed about dose and response or when the proper toxicological risk assessment is not
performed, dangerous conclusions can be made, and this can lead to the perception of risk, the creation of
fear, and the spread of misinformation.
Dose
Dose, by definition is the amount of a substance administered at one time. However, other parameters are
needed to characterize the exposure to xenobiotics. The most important considerations are the amount of
each dose, the number of doses, frequency, and the total duration of the treatment.
Substances can enter the body from either:
1. Encountering them in the environment (exposure).
2. Intentionally consuming or administering a certain quantity of a substance.
Environments in which xenobiotics are present include outdoor air, indoor air, and water. Exposure to a
xenobiotic can occur in any environment where a substance can enter the:
• Skin through absorption
• Respiratory tract through inhalation
• Digestive tract through ingestion
Exposure & Dose
Measuring the amount of a substance a person encountered in the surrounding environment often is
difficult, but a person’s exposure to a xenobiotic can be estimated by collecting samples from the
environment and analyzing which substances are present in them and at what amounts.
For example, when a contaminant is taken into the body via inhalation, the amount that gets into the body
in a biologically available form is called the dose. There are a few different ways to measure the dose.
Potential dose is the amount of contaminant inhaled, not all of which is absorbed.
Applied dose is the amount of contaminant at the absorption barrier (e.g. respiratory tract) that can be
absorbed by the body.
Internal dose is the amount of contaminant that gets past the exchange boundary (lung for inhaled
substances) and into the blood or the amount of the contaminant that can interact with organs and tissues
to cause biological effects.
Biologically effective dose is the amount of contaminant that interacts with the internal target tissue or
organ.
Dose calculation = Exposure Amount (in milligrams)/Body Mass in kilograms
Frequency and Duration of Exposure
• How often is the worker potentially exposed?
• What is the length of time the worker is potentially exposed?
Toxicokinetics: the study of how toxicants get into the body and what happens once they are in the body.
Four processes are involved in toxicokinetics:
Absorption – how a substance makes it from the route of exposure to the circulation (absorption into
bloodstream)
Distribution – how a substance is distributed throughout the body (from the bloodstream to the tissues)
Biotransformation – the body changes (transforms) the substance into new chemicals (metabolites)
Excretion – the substance or its metabolites leave the body (e.g. urine or feces)
Local and Systemic Toxicity
Chemicals can cause many types of toxicity by a variety of mechanisms. Some act locally such as when
direct exposure triggers skin or eye irritation, whereas other chemicals cause systemic effects in the body
in sites remote from where the actual exposure occurred. Toxicity can act directly on subcellular
components, such as cell receptors, or it can cause problems at the cellular level, such as with exposures
to caustic or corrosive substances.
For example, chemicals might:
• Be toxic or require metabolism (chemicals change within the body) before they cause toxicity
• Cause damage leading to fibrosis as the body attempts to repair the toxicity
• Damage or disrupt an enzyme system or protein synthesis
• Produce reactive chemicals in cells
• Cause changes in hormone signaling or other effects
• Produce DNA damage or epigenetic changes
Some chemicals may also act indirectly by:
• Modifying an essential biochemical function
• Interfering with nutrition
• Altering a physiological mechanism
Individual dose-response factors
Toxicokinetics is essentially the study of “how a substance gets into the body and what happens to it in the
body.” Before this term was used, the study of the kinetics (movement) of chemicals was originally
conducted with pharmaceuticals and the term pharmacokinetics became commonly used. Similarly,
toxicology studies were initially conducted with drugs. Toxicokinetics deals with what the body does with a
drug when given a relatively high dose relative to the therapeutic dose.
Toxicological Risk Assessment
Toxicology provides critical information and knowledge that can be used by regulatory agencies, decision
makers, and other to put programs and policies in place to limit our exposures to these substances. These
changes will help in preventing or reducing the likelihood of that a disease or other negative health
outcomes would occur. To determine whether a substance is present or could present a risk to human
health, we begin by collecting information about the substance, the process, and the individual.
The main risk assessment processes when looking at potential toxins are:
1. Hazard identification – characterization of innate adverse toxic effects of agents.
2. Dose-response assessment - characterization of the relationship between doses and incidences of
adverse effects in exposed populations.
3. Exposure assessment – measurement or estimation of the intensity, frequency, and duration of
human exposures to agents.
4. Risk characterization – estimation of the incidence of health effects under the various conditions of
human exposure.
Hazard Identification
One great place to start with the hazards assessment is investigating the substance that the worker could
potentially be exposed to. A toxic substance is simply a material that has toxic properties. It may be a
discrete toxic chemical or a mixture of toxic chemicals.
Information about the physical and health hazards associated with a substance can be found on the Safety
Data Sheet (SDS)
Section 2 – Hazards Identification
Section 11 – Toxicological information includes
• Likely routes of exposure
• Description of delayed, immediate, or chronic effects from short and long-term exposure
• Measures of toxicity (e.g.LD50)
• Description of symptoms
• Indication of whether the chemical is included in a list of carcinogenic substances (IARC
Monographs)
How do we estimate toxicity?
The dose-response relationship is an essential concept in toxicology. It correlates exposures with changes
in body functions or health. In general, the higher the dose, the more severe the response. The dose-
response relationship is based on observed data from experimental cell, animal, and human clinical
studies.
This video provides a good introduction to dose-response.
□ Watch – What the heck is dose response?
Dose Response Assessment
Toxicological studies will produce a graph that represents the physiological response of the organism to
increasing doses of a substance. The most common measurements:
Effective dose (ED50): Dose at which 50% of the subjects experience the desired effect (e.g. pain relief)
Toxic Dose (TD50): Dose at which 50% of the subjects experience a toxic effect (e.g. liver damage)
Lethal Dose (LD50): Dose of the substance that kills 50% of the subjects
Next, we will review how to compare LD50 values in experimental animals to an average (70kg) adult human.
NOTE: the lower the LD50, the more toxic the substance (because you need less of it to cause death).
Exposure Limits
The American Conference of Industrial Hygienists (ACGIH) uses toxicological studies to inform guidelines
regarding safe levels of exposure to various chemical substances and physical agents found in the workplace.
Threshold Limit Values (TLVs) are based on the no-effect area of the dose-response curve. It is important to look
at the column that represents the route of exposure known for the chemical. The threshold limit value of a
chemical substance is believed to be a level to which a worker can be exposed day after day for a working
lifetime without adverse effects.
There are three different types of TLVs as shown here.
Results from research studies establish the highest doses at which no toxic effects were identified and the
lowest doses at which toxic or adverse effects were observed. The terms often used to describe these outcomes
are:
• NOAEL – Highest dose at which there was not an observed toxic or adverse effect.
• LOAEL – Lowest dose at which there was an observed toxic or adverse effect.
Ontario has Occupational Exposure Limits (OELs) for approximately 725 substances. OELs restrict the amount
and length of time a worker is exposed to airborne concentrations of hazardous biological or chemical agents.
These values are based on the ACGIH TLVs. Make yourself familiar with how to find an exposure limit for a
substance.
Actual vs. Perceived Risks
It is also important to be aware of that workers may perceive a risk even when the risk assessment and
toxicological data may not indicate a health hazard.
Factors that decrease the perception of risk:
• Provide information and training for new substances
• Provide choice or make use of hazard voluntary
• Demonstrate the benefits of using the substance
• Use natural versus synthetic if possible
• Create certainty and provide structure
• Make the situation as fair as possible
As a way to reinforce the lesson from this week, choose a product listed below. Think about the ways this
could be beneficial to your health at a particular dose. Would this change if you were exposed for a longer
period of time or more frequently? What about if the dose was doubled or administered 10 times more than
what you originally took?
• Salt (Sodium Chloride)
• Alcohol (Ethanol)
• Tylenol (Acetaminophen)
• Taurine
• Vitamin D
• Caffeine
• Antibiotics
• Sleep aids
• Psilocybin
• Lysergic acid Diethylamide (LSD)
• Morphine
If you have any questions please contact me at cjohns23@uwo.ca
Kind Regards,
Charis
