Environmental Toxicology

1. Chapter 3
Environmental Toxicology

2. Learning Objectives
By the end of this chapter the reader will be able to:
• Define the term toxicology
• Define three important terms used in the field of
toxicology
• State five factors that affect responses to a toxic
chemical
• Discuss the steps involved in risk assessment
• Describe methods for human exposure
assessment

3. Basic Assumption of
Toxicology
• All substances are poisons; there is none that is
not a poison. The right dose differentiates a
poison from a remedy.

4. Definition of Toxicology
• Toxicology is defined as “the study of the
adverse effects of chemicals on living
organisms.”
• Can be applied to all organisms, not just
humans
o Studies are conducted “in vivo” (living organisms) and “in
vitro” (test tubes)

5. History of Toxicology
Paracelsus
• One of the founders of modern
toxicology.
• Active during the time of da Vinci and
Copernicus (early 16th century).
• His contributions included the concept
of the dose-response relationship and
the notion of target organ specificity of
chemicals.
Paracelsus (1493–1541)

6. History of Toxicology
Mathieu Orfila
• Authored a number of significant works
in 1800s, among them Trait des
poisons (1813).
• Described various types of poisons and
their bodily effects
• Contributed to the foundations of
forensic toxicology
Mathieu Orfila (1787-1853)

7. What is a Toxicologist?
• A scientist who has received extensive training in order
to investigate in living organisms “the adverse effects
of chemicals . . . (including their cellular, biochemical,
and molecular mechanisms of action) and assess the
probability of their occurrence.”

8. Fields within Toxicology
• Regulatory
• Forensic
• Clinical
• Environmental
• Reproductive
• Developmental
Environmental toxicology examines how environmental
exposures to chemical pollutants may present risks to
biological organisms, particularly animals, birds, and fish.

9. Toxicology Terms
The spectrum of toxic dose describes the range of
hazards that are related to exposure to a particular
chemical.
Poison
• “defined as any agent capable of producing a deleterious
response in a biological system.”
Toxic Agent
• Very general term to describe a material or factor that can
be harmful to biological systems.
Toxicity
• Refers to “the degree to which something is poisonous.”
• Related to a material’s physical and chemical properties

10. Toxicology Terms
Toxicants
• Toxic substances that are man-made or result from
human (anthropogenic) activity.
Toxin
• Usually refers to a toxic substance made by living
organisms including reptiles, insects, plants and
microorganisms.
• Some toxic plants include: (Next slide from L to R)
o Some mushrooms (e.g., Amanita phalloides, “death cap”)
o Poison hemlock
o Foxglove
o Poison oak/poison ivy
o Rhubarb, especially the leaves, which have high levels of oxalates
o Some houseplants such as dieffenbachia

11. Examples of Toxic Plants

12. Dose
• Refers to “the amount
of a substance
administered at one
time.”

13. Lethal Dose 50 (LD50)
• To describe toxic effects,
toxicologists use the symbol
LD50, which is “the dosage
(mg/kg body weight) causing
death in 50 percent of exposed
animals.”
• Used to compare the toxicities
of different chemicals.

14. Dose-Response
Relationship
• A type of correlative relationship between “the
characteristics of exposure to a chemical and the
spectrum of effects caused by the chemical.”
• This relationship can help establish:
o Casual association between a toxin and biological effects
o Minimum dosages needed to produce a biological effect
o Rate of the accumulation of harmful effects

15. Dose-Response Curve
• A type of graph used to describe the effect of
exposure to a chemical or toxic substance upon an
organism such as an experimental animal.
• Two types of dose-response curves are:
o One for the responses of an individual to a chemical
o One for a population

16. Figure 3-5 Individual dose–response curve.
Source: Reprinted with permission from AE Marczewski, M Kamrin. Toxicology for the Citizen. 2nd ed. East Lansing, Mich: Michigan State University, Center for
Integrative Toxicology; 1991:5. .

17. Figure 3-6 A population dose–response curve.
Source: Adapted from
Guidelines for
Ecological Risk
Assessment. US
Environmental
Protection Agency,
Risk Assessment
Forum. Washington,
DC,
EPA/630/R095/002F;
1998:81.

18. Figure 3-7 The threshold of a dose–response curve.
• Refers to the lowest dose at which a particular
response may occur.
Source: Reprinted
from National
Institutes of
Health, National
Institute of
Environmental
Health Sciences.
Chemicals, the
Environment and
You: Explorations
in Science and
Human Health, p.
63. Available at:
http://science.educ
ation.nih.gov/supp
lements/nih2/che
micals/guide/pdfs/
lesson3.pdf.
Accessed
February 25,
2010.
Threshold

19. Factors That Affect the
Concentration and Toxicity of a
Chemical
• Route of entry into the body
• Received dose of the chemical
• Duration of exposure
• Interactions that transpire among multiple chemicals
• Individual sensitivity

20. Most Frequent Sites of Exposure to
Environmental Chemicals
Gastrointestinal tract
• Ingestion (e.g., consumption
of contaminated food or
drink)
Respiratory System
• Inhalation
Skin
• Injections into the
bloodstream
• Contact with the surface of
the skin (topical mode)

21. Length and Duration of
Exposure
Acute – Usually a single exposure for less than 24 hours
Subacute – Exposure for one month or less
Subchronic – Exposure from one to three months
Chronic – Exposure for more than three months

22. Effects of Chemical Mixtures
Exposures to chemicals in the real world are usually to
multiple chemicals, not just one.
• Additive means that the combination of two
chemicals produces an effect that is equal to their
individual effects added together.
• Synergism indicates that the combined effect of
exposures to two or more chemicals is greater than
the sum of their individual effects.

23. • Potentiation happens when one chemical that is
not toxic causes another chemical to become more
toxic.
• Colative interaction exists when several non-toxic
components mix and produce a toxic effect.
• Antagonism means that “two chemicals
administered together interfere with each other’s
actions or one interferes with the action of the
other.”
Effects of Chemical Mixtures

24. Individual Responses
Responses to toxic substances can very greatly due to
many variables such as:
o age, sex, weight, health condition, genetic background, use
of medication or alcohol, allergies, and/or pregnancy
Direct Adverse Effects of Exposure to Chemicals
• Local effects - damage at the site where a chemical first
comes into contact with the body.
• Systemic effects - generalized distribution of the chemical
throughout the body by the bloodstream to internal organs.
• Target organ effects - some chemicals may confine their
effects to specific organs.

25. Latency
• The time period between initial exposure and a
measurable response.
• The latency period can range from a few seconds
(in the case of acutely toxic agents) to several
decades for agents that may be carcinogenic.
o A chemical (or substance) that causes or is suspected of
causing cancer, a disease associated with unregulated
proliferation of cells in the body.

26. Testing for Toxicity
• The subjects used for testing the toxicity of
chemicals include the following:
o Volunteers who have had normal or accidental
exposures
o Animals exposed purposively (in vivo
experiments)
o Cells derived from human, animal, or plant
sources (in vitro experiments)

27. Risk Assessment
• Provides a qualitative or quantitative estimation of
the likelihood of adverse effects that may result
from exposure to specified health hazards or from
the absence of beneficial influences. (Figure 3-10
next slide)
• Many definitions or perceptions of risk exist
• Psychology Professor Paul Slovic proposed putting
risk into two major comparative factors:
o Dread Risk (factor 1) and Unknown Risk (factor 2)
• see next slide for examples

28. Risk Assessment

29. Process of Risk
Assessment
1. Hazard identification
2. Dose-response assessment
3. Exposure assessment
4. Risk characterization
Described in detail
over the next 5 slides

30. Hazard Identification
• Definition: hazard
o “Inherent capability of an agent or a situation to have an adverse
effect on human life, health, property, or activity, with the
potential to cause a DISEASE, EPIDEMIC, ACCIDENT, or
DISASTER.”.”
• Hazard identification: “examines the evidence that
associates exposure to an agent with its toxicity and
produces a qualitative judgment about the strength of
that evidence…”

31. Dose-Response Assessment
• Measures “the relationship between the amount of
exposure and the occurrence of the unwanted
health effects.”

32. Exposure Assessment
• The procedure that “identifies populations exposed to
the toxicant, describes their composition and size,
and examines the roots, magnitudes, frequencies,
and durations of such exposures.”
• One of the weakest aspects of Risk Assessment
o May pieces have to come together to formulate a conclusion

33. Exposure Assessment
• Attempts to answer the following questions:
– Who or what is exposed (e.g., people, aquatic
ecosystems)?
– Does the exposure occur through breathing air, drinking
water, skin contact or any other routes?
– How much exposure occurs?
– How often and for how long does exposure occur, that
is, what is its frequency and duration?

34. Risk Characterization
• Develops “estimates of the number of excess
unwarranted health events expected at different time
intervals at each level of exposure.”
• Provides the necessary information to the policy
maker to make adjustments (or not) to a process to
reduce the risk to humans.

35. Risk Management
• Oriented toward specific actions and “consists
of actions taken to control exposures to toxic
chemicals in the environment.
• Exposure standards, requirements for
premarket testing, recalls of toxic products, and
outright banning of very hazardous materials
are among the actions that are used by
governmental agencies to manage risk.”

36. Overview of Risk Assessment