Graduate School of Public Health
San Diego State University
Division of Environmental Health
PRINCIPLES OF TOXICOLOGY (PH 638A)
Spring 2013
Class time/location: Tu 1300-1540, HH122
Instructor: Penelope JE Quintana, PhD, MPH
Contact phone/email: 619-594-1688, jquintan@mail.sdsu.edu email much preferred!
Office location: HT 104. Office hours Tuesdays 11:00 – 12:30 or by appt.
Course goals and learning objectives: The goal of this course is to give students instruction and practice
with the basic tools to address issues related to chemical toxicity. Students who successfully complete this
course should be able to:
1.
Explain and apply general principles of toxicology.*,**
2.
Describe basic pathophysiology of major mammalian organ systems associated with overexposure to
some of the more important chemicals (pesticides, solvents, drugs, natural products, etc) we encounter
in our environment.*
3.
Demonstrate ability to research primary and other toxicology literature sources, critically evaluate and
synthesize information from this literature, and communicate effectively in writing on issues related to
the toxic effects of chemicals in the home, workplace, and ambient environments.**
*Assessed by exam performance.
**Assessed by position paper grade.
Required text and location of other course materials:
Principles and Practice of Toxicology in Public Health
Ira S. Richards (Author)
Paperback: 464 pages
Publisher: Jones & Bartlett Publishers; 1 edition (October 5, 2007)
Language: English
ISBN-10: 0763738239
ISBN-13: 978-0763738235
Class notes, readings etc. are provided through the course Blackboard site.
Course requirements, evaluation and grading: Final course grade will be based on the following:
1.
2.
3.
Two exams (30% each x 2 = 60%).
Position paper (25% paper, 5% oral presentation).
Regular attendance and class participation, incluing short pass/no pass assignments (10%).
Final course grades will be assigned as follows based on total points accumulated for the semester:
B+ = 86-89
C+ = 75-77
Letter grade range
A = 93-100
B = 81-85
C= 71-74
F=<68
A- = 89-93
B- = 77-80
C- = 68-70
Course syllabus subject to change. Every effort will be made to follow the syllabus content and course
calendar, although extenuating circumstances may require modifications in the planned initial schedule. It is
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the students’ responsibility to check Blackboard regularly for new information; however, the instructor will
make every reasonable effort to notify students of changes in a timely manner.
Course Policies
Class attendance. Please try hard to be in your seat by 1:00 p.m. Latecomers are disruptive to the entire
class and distracting to the instructor. Chronic late arrivals may count against the attendance portion of your
grade.
Religious holidays. The University Policy File includes the following statement on absence for religious
observances: By the end of the second week of classes, students should notify the instructors of affected
courses of planned absences for religious observances.
Extenuating circumstances. If serious difficulties (severe illness, injury, death of a family member) prevent
you from attending class or completing an assignment on time, please contact the instructor as soon as possible
to discuss alternative arrangements.
SDSU Policies
San Diego State University is dedicated to a safe, supportive and nondiscriminatory environment. It is the
responsibility of all students to familiarize themselves with University policies regarding nondiscrimination,
misconduct and academic honesty.
Statement on Nondiscrimination Policy
San Diego State University complies with the requirements of Title VI and Title VII of the Civil Rights Act of
1964, as well as other applicable federal and state laws prohibiting discrimination. No person shall, on the
basis of race, color, or national origin be excluded from participation in, be denied the benefits of, or be
otherwise subjected to discrimination in any program of the California State University
SDSU does not discriminate on the basis of disability in admission or access to, or treatment or employment in,
its programs and activities. Students should direct inquiries to the Student Disability Services (SDS).
SDSU does not discriminate on the basis of sex, gender, or sexual orientation in the educational programs or
activities it conducts.
More detail on SDSU’s Nondiscrimination Policy can be found in the SDSU General Catalog, University
Policies.
Student Conduct and Grievances
SDSU is committed to maintaining a safe and healthy living and learning environment for students, faculty and
staff. Sections 41301, Standards for Student Conduct, and Sections 41302-41304 of the University Policies
regarding student conduct should be reviewed.
If a student believes that a professor’s treatment is grossly unfair or that a professor’s behavior is clearly
unprofessional, the student may bring the complaint to the proper university authorities and official
reviewing bodies. See University policies on Student Grievances.
Statement on Plagiarism and Academic Dishonesty
Academic dishonesty includes cheating, plagiarism or other forms of academic dishonesty that are intended to
gain unfair academic advantage. See section 41301 of the University policies. Plagiarism is an important
element of this policy. Plagiarism is defined as ‘formal work publicly misrepresented as original; it is any
activity wherein one person knowingly, directly and for lucre, status, recognition, or any public gain resorts to
the published or unpublished work of another in order to represent it as one’s own’. Any work, in whole or in
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part, taken from the Internet or other computer-based source without referencing the source is considered
plagiarism.
Turnitin
Nobody wants to be suspected of plagiarism, much less actually caught using material verbatim without
appropriate attribution. The internet is a huge time-saver in terms of access to information, but the ability to cut
and paste and “borrow” text from published and other publicly available online sources is a potentially
dangerous feature enabled by the internet that causes many universities great concern. Ideas and other
information included in papers turned in for grading must be appropriately referenced and expressed in your
own words. The instructor has found that using the Turnitin feature of Blackboard benefits both students and
instructors. One feature of Turnitin allows students to check for textual similarity to other sources before
submitting papers for grading. How to access Turnitin and what constitutes “crossing the line”, and how to
avoid it will be discussed in class. You should find more advice and information about checking drafts in the
Assignments/Turnitin section of the course Blackboard.
Please be advised of the following SDSU policy: Students agree that by taking this course all required papers
and exams, as applicable, may be subject to submission for textual similarity review to Turnitin for the
detection of plagiarism. All submitted papers will be included as source documents in the Turnitin reference
database solely for the purpose of detecting plagiarism of such papers. You may submit your papers in such a
way that no identifying information about you is included. Another option is that you may request, in writing,
that your papers not be submitted to Turnitin. However, if you choose this option you will be required to
provide documentation to substantiate that the papers are your original work and do not include
any plagiarized material.
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Principles of Toxicology
Schedule of PH 638A Topics and Assignments – Spring 2013
Students who are not already familiar with the many ways toxicology and related literature can be accessed through the
SDSU library system should notify the instructor during the first two weeks of class. Topic-targeted search help may be
offered by Marilyn Hall, Love Library Public Health reference librarian, time permitting.
Week
1
2
3
4
Dates
1/22
1/29
2/5
2/12
5
6
2/19
2/26
7
3/5
8
3/12
9
3/19
10
3/26
Topics
Principles Definitions, principles and concepts
Principles ADME, Toxicokinetics
Principles Toxicokinetics (cont’d) and biotransformation
Principles Biotransformation, cont’d, Chemical Mutagenesis and
Carcinogenesis
(**Select position paper topic by this date.**)
Principles Genotoxicity, biological monitoring
Application Biological monitoring and biomarkers, cont’d, CDC
National Report
Systemic Toxicity Neurotoxicity and pesticides, liver and kidney
toxicity (EXAM ‘HANDED OUT’ in Blackboard today)
No in class meeting****Exam I **** (take home ,due at end of
class today, uploaded to Blackboard or in front office)
(Dr. Quintana at meeting NC.)
Systemic Toxicity Dermal / Respiratory / cardiovascular toxicity
Application
Systemic Toxicity Clinical Toxicology, Teratogens and CTIS
Chapters in text
1, 2 3, 5,6
7,8
7,8,9
9, 10,11
10, 11 cont
Reading
Reading, 11
Reading
13, 15, 16
Robert J. Felix
Teratogen Information Specialist
CTIS Pregnancy Health Information Line
University of California, San Diego
School of Medicine, Department of Pediatrics
11
12
4/2
4/9
4/16
13
4/23
No class - spring break week
Regulatory Toxicology / Toxicity Testing
Systemic Toxicity Developmental and reproductive toxicity
14, 17
19, 20
Stephen B. Harris, Stephen B. Harris Group
Application New Frontiers (toxicogenomics, RNAi, and more!)
Amy Yang,
Pfizer Worldwide Research & Development, La Jolla Labs
14
4/30
****Position papers due****
Student Presentations
15
5/7
**** Exam II ****
Finals
week
5/14
Student Presentations (if needed).
*
Lecture schedules, reading and due dates may be modified without warning.
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PRINCIPLES OF TOXICOLOGY (PH 638A)
POSITION PAPER TOPICS
Below is a list of approved position paper topics for PH638A. Alternatives are negotiable; however, before proposing
another topic, please make sure that your proposed topic (1) is of current interest and importance (i.e., not a "dead issue" or
lacking widespread consensus already; for example, is cigarette smoking bad for you?); (2) is stated in the form of a specific
question to be addressed, and (3) requires that some judgment be made based on a review of the pertinent scientific
literature. Discuss any questions you have with the instructor before beginning an exhaustive literature search.
Only one student may write on a given topic each year. First come first served. Use the class Blackboard Discussion
feature to reserve your topic. Check to see if your topic has already been selected and then post your selection. Others
posting later will be expected to steer clear of your topic, and to make sure your choice is not overlooked you should
indicate the topic number and a key word in the subject of your posting (not just ‘my paper topic’). All students must have
a topic by the week shown on the course schedule. Papers must follow PH638A paper guidelines detailed in a separate
handout. Examples from past years will be available on the course Blackboard. Topics of papers posted cannot be selected.
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Does dioxin cause cancer in humans and should it be regulated like a "typical" carcinogen? Justify your answer on
the basis of epidemiological, toxicological and mechanistic studies.
Is exposure to estrogenic and anti-estrogenic pollutants and naturally occurring substances in our
environment seriously affecting human health? Consider evidence from both epidemiological and toxicological
studies.
What are the probable agents responsible for the acute and chronic respiratory illnesses reported by disaster
relief workers and lower Manhattan residents near the 9/11 disaster site? Discuss the symptoms and consider
the toxicology of specific agents and that could be linked them.
Describe Gulf War Syndrome and discuss the toxicological and epidemiological evidence pro and con that is may
be due to exposure to toxic chemicals.
What is the evidence that environmental agents cause Alzheimer's disease? Cite any toxicology studies that
provide convincing evidence (either pro or con)?
What toxicological evidence is there that exposure to cholinesterase inhibitor pesticides may adversely affect
birth outcome?
Does regular daily maternal intake of caffeine in coffee adversely affect the fetus?
Phthalate esters are used as plasticizers, and as such are found in many types of plastics including pipes, packaging
materials and food containers. They are ubiquitous in the environment. Should we be concerned about the effects
of phthalate esters on fertility?
Of all of the chemicals known or suspected to disrupt endocrine function, bisphenol A is currently among the most
controversial in terms of how it should be regulated. Research and discuss the basis for this controversy, and state
your opinion on whether you agree with the direction proposed regulations are headed.
Has semen quality changed over this century and, if, so, could this be a result of exposure to chemicals in our
environment? Research the evidence and decide for yourself.
Acute carbon monoxide poisoning is responsible for most of the chemically related accidental deaths in the U.S.
Sometimes a person who has ostensibly recovered suddenly dies several weeks after the exposure. Do we know
exactly what causes this delayed effect?
Are the flavonoids found in numerous fruits and vegetables mutagenic and otherwise toxic in large doses, or are
they necessary and useful components of our diets? How would you advise your vegetarian friend who asks about
this, and how would you label these foods to provide warnings to people if that were deemed necessary by the
FDA?
Should fluoridation of drinking water be considered safe for all age groups?
Does drinking chlorinated water lead to increased risk of adverse birth outcomes? Discuss both
epidemiological and toxicological literature.
Are levels of perchlorate in some of our drinking water supplies harmful to the general public? Discuss sources
of perchlorate, potential toxicological effects, levels in the environment, and epidemiologic studies that address this
issue.
Perflouorooctanoic acid (PFOA) is a vital processing aid in the manufacture of nonstick coatings, such as
Teflon found in cookware. Discuss the evidence that trace amounts left over in final products might be hazardous
to the health of people who regularly eat food prepared in nonstick cookware.
Should people be careful about ingesting large doses of natural products as dietary supplements or drugs?
Discuss the safety studies of one listed here and decide whether it should be regarded as a safe product. St. John’s
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wort, ginko biloba, gensing, kava. You must pick just one and do a complete job with researching and
discussing that one.
Can consumption of aflatoxins be the sole cause of liver cancer in some countries of the world? Justify your
answer with the latest toxicological and epidemiological studies.
Select one of the following chemical products, research its history of toxicity testing and regulation, and decide
whether it has been regulated appropriately (i.e., based on good, sound science): chloroform, saccharin,
Alar, MTBE. 1,3,-butadiene
Should Californians be concerned about eating shellfish containing domoic acid? Discuss the toxicity of this
chemical, levels typically found, the outbreaks, and their aftermath.
Is the Maximum Tolerated Dose (MTD) a meaningful dose of a chemical to test in animal cancer bioassays?
Discuss arguments pro and con and decide whether you would recommend any changes in dose selection for the
typical cancer bioassay.
Should we stop eating delicious charcoal broiled hamburgers? In your answer, discuss specific mutagenic
chemicals formed during the cooking of beef to account for its mutagenic activity, toxicology studies of effects,
and optimal conditions for cooking hamburger and other meats to minimize production of mutagenic substances.
What is the difference in health effects, if any, between smoking tobacco cigarettes and breathing secondhand
smoke? Discuss specific chemical components in each type of exposure as well as any rigorously controlled
laboratory-based health effects studies of each.
What are some of the false-positives and false-negatives encountered in testing chemicals for teratogenic
properties? If the current FDA procedures were used in 1950, would the thalidomide disaster have been averted?
Are there any effective treatments for chronic poisoning by environmental toxicants (e.g., chelation therapy,
detoxifying baths to "steam out poisons", etc.) or are claims made by proponents of these treatments somewhat
overstated?
Does the correlation between mutagenicity in short-term tests and animal carcinogenicity? Discuss
approaches used by studies to answer this question, including strengths and weaknesses, and decide whether shortterm mutagenicity tests have a future in toxicology health hazard evaluations.
How strong is the correlation between animal carcinogenicity and human carcinogenicity? Discuss evidence
from animal cancer bioassays and epidemiological studies and discuss what you think the future role of animal
cancer bioassays should be in human health risk assessments.
Is measuring DNA adducts in human blood or other tissue samples constitute good evidence that a person was not
only exposed to a genotoxic agent but also is at risk of a genetically-related disease due to that exposure? Discuss
what DNA adducts mean, epidemiological studies using DNA adducts as biomarkers (see, for example, aflatoxin),
and correlation of this marker with disease incidence.
Employees at a popcorn plant working with butter flavorings developed a rare severe lung disease. What was
this attributed to? Discuss toxicological evidence that this was indeed the disease agent.
Will a high intake of vitamin A provide any protection for smokers against lung cancer? Cite well-controlled
lab studies as well as epidemiology studies, and mention any known hazards of excessive Vitamin A intake.
Does exposure to PCBs cause altered immune function in human populations?
What is the prognosis for survivors who inhaled particulates resulting from the destruction of the World Trade
Center towers on 9/11/01? Make your decision based on the types of diseases and disease agents that have been
well documented thus far and the severity and reversibility of these diseases.
Should one be concerned about cancer following high exposures to methylene chloride if one is not a mouse?
Elaborate, discussing the risk levels and whether or not there seems to be a "safe" dose.
What is the chance that offspring of parents exposed to dioxin will experience any lasting effects? Review the
toxicology literature to see if it supports or refutes epidemiological studies, including follow up of victims of the
Seveso incident.
Is the current lead standard for drinking water safe for children? Justify your answer. Consider differences in
size, consumption and sensitivity relative to adults.
Are acrylamide levels in a variety of foods a major public health concern? Discuss the toxicity and potential risks
of this chemical in relation to concentrations commonly found in foods.
Mercury in tuna is not a new issue. However, recent attention has been directed toward the consequences of
mercury intake by children, who are obviously smaller than adults, and who might regularly eat canned tuna.
Discuss scientific studies that look at this issue and make a determination as to how much canned tuna should be
considered safe for children to consume.
Is the State of California justified in banning use of certain polybrominated diphenyl ethers? What are these
compounds used for, what are their potential health effects, and specifically why have scientists and regulators
become concerned?
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39. Health effects expected with BP oil spill: Review and evaluate studies that predict the long-term effects of this
environmental disaster. In addition to reviewing effects predicted important questions you should address include
whether there enough information now to predict long term effects and if not then what studies are needed?
IMPORTANT: You may choose to focus on either human health or ecological imacts of this particular issue but
do not attempt to cover both in this paper. Focus on one of these and address all of the related questions
thoroughly and in more depth.
40. Many novel uses for nanoparticles have been discovered over the past decade, resulting in a huge increase in
exposure potential for researchers, manufacturers, and other users of nanoparticles. Are the health effects of
exposure to nanoparticles sufficiently well documented to provide appropriate health warnings to potentially
exposed individuals?
41. Atrazine, a pesticide, has been implicated in water sources in the Midwest, and has been shown to occur at high
peak values, although it is regulated as an average. What is the evidence that atrazine occuring in high peak levels
might be more toxic than might be expected from toxicity at average levels? Should the EPA change monitoring
requirements?
42. Halomethanes are potentially toxic chemicals that can occur in rainwater treated for consumption. How are these
formed, and should persons treating stored rainwater be concerned?
43. Air pollution has long been known to cause adverse respiratory and cardiac problems. More recently, adverse
effects on the fetus have been reported when pregnant women are exposed to air pollution. Should pregnant
women be concerned about air pollution? What agents, if any, might they be concerned about?
44. Is there evidence that exposure to heavy traffic causes cancer (lung cancer or leukemia, pick one) Should
change our urban planning based on this data?
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PRINCIPLES OF TOXICOLOGY POSITION PAPER GUIDELINES
CONTENT.
These assignments are called position papers because they require statement of an opinion after a
comprehensive and critical literature review. Papers should focus on the specific question being
addressed and provide a clear answer to the question. Opinions should be based on objective scientific
evidence and also be appropriately referenced. Recognizing that definitive clinical or epidemiological
studies are clearly important for assessing human risk, it is expected that papers for this course will
focus on relevant peer-reviewed experimental toxicology studies when such exist. Epidemiological
studies should also be presented, where relevant.
Papers may not exceed a maximum of 8 double-spaced typed pages, not including title page or
references. 10 pitch font is OK but nothing smaller. Do not skimp on margins.
FORMAT.
Papers that do not have the following format may be returned for revision with penalty points for
lateness due to need for revision. Use the headings shown. Subheads are also often useful.
.
.
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.
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TITLE PAGE: A brief title using keywords indicating the question being addressed (e.g.,
"Arsenic and human cancer"), your name, the course number, and the date. This page must be
included only with the hard copy of your paper submitted in class on the due date. Omit the
title page when you submit papers through SafeAssign.
INTRODUCTION (p. 1): State the question being answered at the top of page 1.
Introductions typically consist of 1-2 short paragraphs of historical background and reason for
posing the question.
BACKGROUND: A concise summary of the scientific literature on the subject, appropriately
referenced. All articles consulted need not be described in detail, particularly if many of them
come to the same conclusion. However, you should demonstrate that you have thoroughly
researched your topic and have made some judgments as to the completeness and quality of
existing toxicological and epidemiological information. The use of additional subheads in a
lengthy review is strongly encouraged as this often makes organization of the paper much
clearer to a reader.
CONCLUSION: Clearly state your conclusions. It should be obvious to the reader by this time
why you reached the conclusion you did. If there is some doubt about this, briefly highlight
studies on which the conclusion was based. A final statement consisting of a recommendation
to the general public or other implications of your findings for public health is often an
appropriate way to end many of these essays.
REFERENCES: Papers not using the APA referencing format (same one required for GSPH
theses) that cites the (author, date) in the text and showing alphabetized citations in the
reference section may be returned for editing. Pay close attention also to details on exactly
how these citations are to be shown in the reference list. Only articles or monographs that were
actually read and referenced in your paper should appear in the reference list. Primary source
basic and applied science journal articles should comprise the largest part of the bibliography
for these assignments, which are meant to be scientifically supported, data-oriented essays.
While brief review articles, popular science articles, textbooks, newspapers and magazine
articles may provide initial inspiration or background for the question you pose, at most one or
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two should be cited. Articles and other sources accessed online and referenced in your paper
should still include full formal citations, not just a URL or online doi number; for example,
journal article references must include journal name, year, volume, beginning and ending page
numbers. Try to avoid use of non peer-reviewed scientific sources.
**Note about SafeAssign and referencing: Originality scores of papers using SafeAssign are
obviously decreased by inclusion of website URLs and sometimes by other references that are
flagged as non original text. If you are concerned about this, first submit a copy of your paper
without the references you will attach later in the final submission, clear up any real issues of
concern in the body of the paper, and then reinsert your references before submitting your final
version for grading. Or, simply use common sense, recognize that the instructor can also see
text that is original and text that is not, and do not stress unnecessarily about your score if
instances of similar text flagged are found in the references section.
EVALUATION Grading will be based on (1) the thoroughness of the research, including
appropriateness and quality of references, (2) organization and presentation of facts, (3) logical
conclusion based on analysis of the data discussed, (4) succinct scientific writing style, good grammar,
and overall effectiveness of the paper.
DUE DATE will be shown in the class schedule. There is plenty of time to complete this paper.
Please do not ask for individual extensions of deadlines for these papers. It is unfair to other students
and paper grades can be reduced for late submission.
OTHER EXPECTATIONS
Do not exceed 8 double-spaced pages for each paper, excluding title page and references.
Do proofread carefully. Use the "spell check" and "grammar" functions of your word processing
program. Evidence of too many typos, incomplete sentences, missing references, etc. may cause your
paper to be returned before it can be graded.
Do not insert tables, graphs, or other unnecessary illustrations in your paper. A possible exception is a
chemical structure if the chemical being discussed is particularly unusual or you will be referring to the
role the structure plays in toxicity.
Avoid the inclusion of direct quotations from other papers even if the source of information is
appropriately referenced and shown in quotes. It is rare in scientific writing to include even a succinct
summary of what the original author said. Normally everything is expressed in your own words and in
your own style of writing.
Do proofread your paper before submission and avoid the following most common grammatical errors
and use of terminology found every year in these papers:
Many papers have a shocking number of errors involving subject:verb agreement!
Many papers have a shocking number of misplaced or extraneous commas! NEVER
SEPARATE A SUBJECT FROM A VERB WITH A SINGLE COMMA OR ANY OTHER
SINGLE PUNCTUATION MARK. THIS INSTRUCTOR MAY GO BALLISTIC IF SHE
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SEES TOO MANY OF EITHER THIS--THE MOST BASIC OF GRAMMATICAL ERRORS-MISTAKES IN SUBJECT VERB AGREEMENT, OR INCOMPLETE SENTENCES. All
would be rarer if grammar check word processing features were used regularly and papers also
proofread carefully before submission, but all are still shockingly numerous.
Do not misspell "separate" (there is "a rat" in separate).
Do not confuse "effect" with "affect". There are toxic effects, a toxicant can effect a change in
blood chemistry, and a given chemical can affect many different organs.
Do appreciate the differences between the terms "hazardous" vs. "toxic", "dose" vs. "exposure",
and "toxicant" vs. "toxin", and use the appropriate terms in your papers. The distinctions will
be discussed in class.
Important specifications abourt the hard copy of the final version and Turnitin copy of the same
version:
You will be expected to provide a hard copy of your position paper on the due date in addition to using
Turnitin to submit the text of the paper only minus the references and without any personal identifying
information.
Hard copies must be stapled (no paperclips, please) and have pages numbered.
PLEASE no plastic or other fancy report covers or other binding. One staple will suffice.