Environmental Sciences

1. Environmental Toxicology
Instructor: Hafiz Mudaser Ahmad
Email: h.m.ahmad@uet.edu.pk
Department of Chemical, Polymer, and Composite Materials Engineering
University of Engineering & Technology (New Campus) Lahore

2. Course Outline
ES-301 Environmental Toxicology
Introduction to Toxicology
• Classification and Properties of toxic substances
• Anthropogenic and natural poisons
• Acute and Chronic effects
• Genotoxic, mutagens, teratogens
• Carcinogenic and sensitizers
• Biological Properties of organic and
inorganic pollutants:
• Essentiality and toxicity
• Routs of absorption
• Bioaccumulation and Biomagnification (Lecture +
Review Article)
Quantification of Toxicology
• Dose response relationships
• Synergism, Antagonism
• LD50 and rating systems
• Threshold limiting values
• Toxic impacts of atmospheric agents
• Fate of absorbed toxins xenobiotics
• Detoxification and Bioactivation
• Natural detoxification processes
• Risk management

3. Course
Assessment
Criteria
Midterm Exam (30%)
First Quiz (10%)
Second Quiz (10%)
Assignment (10%)
Final Term Exam (40%)

4. Lecture Outline
• INTRODUCTION TO ENVIRONMENTAL TOXICOLOGY
• Different areas of toxicology
• Mechanistic toxicology
• Regulatory toxicology
• Descriptive toxicology
• Toxicology and society
• General characteristics of the toxic response
• History of Toxicological studies
• CLASSIFICATION OF TOXIC AGENTS

5. INTRODUCTION TO ENVIRONMENTAL
TOXICOLOGY
• Toxicology is the study of the adverse effects of chemicals or
physical agents on living organisms.
• A toxicologist is trained to examine and communicate the
nature of those effects on humans, animals, and
environmental health.

6. INTRODUCTION TO ENVIRONMENTAL
TOXICOLOGY
• Toxicological research examines the cellular, biochemical,
and molecular mechanisms of action as well as functional
effects such as neurobehavioral and immunological and
assesses the probability of their occurrence.
• Fundamental to this process is characterizing the relation
of exposure (or dose) to the response.

7. INTRODUCTION TO ENVIRONMENTAL
TOXICOLOGY
• Risk assessment is the quantitative estimate of the potential
effects on human health and environmental significance of
various types of chemical exposures (e.g., pesticide residues
in food, contaminants in drinking water).

8. INTRODUCTION TO ENVIRONMENTAL
TOXICOLOGY
• The variety of potential adverse effects and the diversity of chemicals
in the environment make toxicology a broad science, which often
demands specialization in one area of toxicology. Our society’s
dependence on chemicals and the need to assess potential hazards
have made toxicologists an increasingly important part of the
decision-making processes.

9. Different Areas of Toxicology

10. Mechanistic Toxicologist
• A mechanistic toxicologist is concerned with
identifying and understanding the cellular,
biochemical, and molecular mechanisms by which
chemicals exert toxic effects on living organisms.

11. Mechanistic Toxicologist
• Mechanistic data may be very useful in identifying adverse responses in
experimental animals that may not be relevant to humans.
• For example, the tendency of the widely used artificial sweetener
saccharin to cause bladder cancer in rats may not be relevant to humans at
normal dietary intake rates. This is because mechanistic studies have
demonstrated that bladder cancer is induced only under conditions where
saccharin is at such a high concentration in the urine that it forms a
crystalline precipitate (Cohen, 1998).

12. Descriptive Toxicologist
• A descriptive toxicologist is concerned directly with toxicity
testing, which provides information for safety evaluation and
regulatory requirements. The appropriate toxicity tests in cell
culture systems or experimental animals are designed to
yield information to evaluate risks posed to humans and the
environment from exposure to specific chemicals.

13. Descriptive Toxicologist
• Toxicologists in the chemical industry, however, must be
concerned not only with the risk posed by a company’s
chemicals (insecticides, herbicides, solvents, etc.) to humans
but also with potential effects on fish, birds, and plants, as
well as other factors that might disturb the balance of the
ecosystem.

14. Regulatory Toxicologist
• A regulatory toxicologist has the responsibility for deciding, on
the basis of data provided by descriptive and mechanistic
toxicologists, whether a drug or other chemical poses a
sufficiently low risk (or, in the case of drugs, a favorable
risk/benefit profile) to be marketed for a stated purpose or
subsequent human or environmental exposure resulting from its
use.

15. Regulatory Toxicologist
• The Food and Drug Administration (FDA) is responsible for allowing drugs, cosmetics, and food
additives to be sold in the market according to the Federal Food, Drug, and Cosmetic Act (FFDCA).
• The US Environmental Protection Agency (EPA) is responsible for regulating most other chemicals
according to a variety of different legislative acts, including:
• Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA)
• Toxic Substances Control Act (TSCA)
• Resource Conservation and Recovery Act (RCRA)
• Safe Drinking Water Act, and the Clean Air Act
• In 1996, the US Congress passed the Food Quality Protection Act (FQPA) that fundamentally
changed the pesticide and food safety laws to consider stricter safety standards, particularly for
infants and children, who were recognized as more susceptible to the health effects of pesticides.

16. Toxicology and Society
• Information from the toxicological sciences, gained by experience or
research, has a growing influence on our personal lives as well as on
human and environmental health across the globe.
• Knowledge about the toxicological effects of a compound that affects
consumer products, drugs, manufacturing processes, waste cleanup,
regulatory action, civil disputes, and broad policy decisions.
• The expanding influence of toxicology on societal issues is
accompanied by the responsibility to be increasingly sensitive to the
ethical, legal, and social implications of toxicological research and
testing.

17. Toxicology and Society (Ethical Dynamics)
• First, experience and new discoveries in the biological sciences have
emphasized our interconnectedness with nature and the need for
well-articulated visions of human, animal, and environmental health.
One vision is that we have “condition(s) that ensure that all living
things have the best opportunity to reach and maintain their full
genetic potential” (Gilbert, 2005a).

18. Toxicology and Society (Ethical Dynamics)
• Second, we have experience with the health consequences of
exposure to such things as lead, asbestos, and tobacco, along
with detailed mechanistic research to understand the long-term
risks to individuals and society. This has precipitated many
regulatory and legal actions and public policy decisions, not to
mention costly and time-consuming lawsuits.

19. Toxicology and Society (Ethical Dynamics)
• Third, we have an increasingly well-defined framework for
discussing our social and ethical responsibilities. There is
growing recognition that ethics play a crucial role in public
health decision-making that involves conflicts between
individual, corporate, and social justice goals (Callahan and
Jennings, 2002; Kass, 2001; Lee, 2002).

20. Toxicology and Society (Ethical Dynamics)
• Fourth is the appreciation that all research involving humans or
animals must be conducted in a responsible and ethical manner.
• Fifth is managing both the uncertainty and biological variability
inherent in the biological sciences. Decision-making often
includes making judgments with limited or uncertain
information, which often includes an overlay of individual values
and ethics.

21. Toxicology and Society (Ethical Dynamics)
• Finally, individuals involved in toxicological research must
be aware of and accountable for their own individual
biases and possible conflicts of interest and adhere to the
highest ethical standards of the profession (Maurissen et
al., 2005; Coble et al., 2009; Gilbert and Eaton, 2009).

22. • Ethical reasoning and philosophy have a long and deep history, but more
pragmatic bioethical reasoning can be traced to Leopold, who is arguably
America’s first bioethicist: “A thing is right when it tends to preserve the
integrity, stability, and beauty of the biotic community. It is wrong when it
tends otherwise” (Leopold, 1949).
• The essence of toxicology is to understand the effects of chemicals on the
biotic community. This broader definition of an ethic became more focused
on examples such as the mercury poisoning in Minamata Bay, Japan,
thalidomide, and the effects of pesticides as brought to public awareness
by Carson’s Silent Spring (Carson, 1962).

23. • On a parallel track, biomedical ethics developed out of the
lessons of World War II and related abuses of human
subjects. The 4 principles of biomedical ethics—respect for
autonomy, beneficence (do good), nonmaleficence (do no
harm), and justice (be fair)—became well established as a
basis for decision-making in health care settings
(Beauchamp and Childress, 1994).

24. General Characteristics of the Toxic Response
• One could define a poison as any agent capable of producing a
deleterious response in a biological system, seriously injuring function
or producing death.
• This is not, however, a useful working definition for the very simple
reason that virtually every known chemical has the potential to
produce injury or death if it is present in a sufficient amount.

25. General Characteristics of the Toxic Response
• Paracelsus (1493–1541), a Swiss/German/Austrian physician,
scientist, and philosopher, phrased this well when he noted,
“What is there that is not poison? All things are poison and
nothing [is] without poison. Solely the dose determines that
a thing is not a poison.”

28. History of Toxicological Studies

32. CLASSIFICATION OF TOXIC AGENTS
• Toxic agents are classified in a variety of ways, depending on
the interests and needs of the classifier.
• Toxic agents are discussed in terms of their target organs
(liver, kidney, hematopoietic system, etc.), use (pesticide,
solvent, food additive, etc.), source (animal and plant toxins),
and effects (cancer, mutation, liver injury, etc.).

33. • The term toxin generally refers to toxic substances that are produced
by biological systems such as plants, animals, fungi, or bacteria.
• The term toxicant is used in speaking of toxic substances that are
produced by or are a by-product of anthropogenic (human-made)
activities.
• Thus, zearalenone, produced by a mold, is a toxin, whereas “dioxin”
(2,3,7,8- tetrachlorodibenzo-p-dioxin [TCDD]), produced during the
production and/ or combustion of certain chlorinated organic
chemicals, is a toxicant.

34. • Some toxicants can be produced by both natural and
anthropogenic activities. For example, polyaromatic
hydrocarbons are produced by the combustion of
organic matter, which may occur both through natural
processes (eg, forest fires) and through anthropogenic
activities (eg, combustion of coal for energy
production; cigarette smoking).

35. • Arsenic, a toxic metalloid, may occur as a natural
contaminant of groundwater or may contaminate
groundwater secondary to industrial activities.
Generally, such toxic substances are referred to as
toxicants, rather than toxins, because, although they
are naturally produced, they are not produced by
biological systems.

36. • Distinguishing a “toxin” from a “toxicant” is not always easy. For
example, many pesticides, such as the pyrethroids, are synthetic
analogs of natural products, such that one would call the
pyrethrum found in the chrysanthemum flower a “toxin,” but the
synthetic (and slightly altered in structure) form produced for use
in pesticide formulations would be a “toxicant.” Thus, although
technically incorrect, many physicians and others involved in the
diagnosis and treatment of poisonings often use the term “toxin”
to refer to any toxic substance, regardless of origin.

37. • Toxic agents may also be classified in terms of their
physical state (gas, dust, liquid, size, e.g.,
nanotoxicology), their chemical stability or reactivity
(explosive, flammable, oxidizer), general chemical
structure (aromatic amine, halogenated hydrocarbon,
etc.), or poisoning potential (extremely toxic, very
toxic, slightly toxic, etc.).

38. • Classification of toxic agents on the basis of their
biochemical mechanisms of action (e.g., an alkylating
agent, endocrine disruptor) is usually more informative
than classification by general terms such as irritants and
corrosives. But more general classifications such as air
pollutants, occupation-related agents, and acute and
chronic poisons can provide a useful focus on a specific
problem.

39. • It is evident from this discussion that no single
classification is applicable to the entire spectrum of
toxic agents and that a combination of classification
systems or a classification based on other factors is
generally needed to provide the best characterization
of a toxic substance.

40. •Nevertheless, classification systems that take
into consideration both the chemical and the
biological properties of an agent and the
exposure characteristics are most likely to be
useful for regulatory or control purposes and for
toxicology in general.