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BIO367 Forensic Toxicology: Unit Information and Learning Guide

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BIO367

Forensic Toxicology

Unit Information and Learning Guide

Semester 2, 2018

This information should be read in conjunction with the online learning materials
which can be found on your MyUnits page.

Unit coordinator
Dr Garth Maker
School of Veterinary and Life Sciences
G.Maker@murdoch.edu.au
© Published by Murdoch University, Perth, Western Australia, July 2018.

This publication is copyright. Except as permitted by the Copyright Act no part of it may in
any form or by any electronic, mechanical, photocopying, recording or any other means be
reproduced, stored in a retrieval system or be broadcast or transmitted without the prior
written permission of the publisher.

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Contents

Unit information
Information about the unit 4
Contact details 6
How to study this unit 7
Resources for the unit 8
Study schedule 9
Assessment 12
Learning guide 15

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Information about the unit
Welcome to BIO367 Forensic Toxicology!

Unit description

This unit has been designed to provide an understanding of the mode of toxic action of
compounds of forensic significance and to provide an overview of the analytical methods
commonly used in forensic toxicology. The toxicology of homicidal agents and the practical
applications of modern analytical techniques to the determination of alcohol, drugs and other
organic and inorganic trace residues in body fluids and contaminated material will be studied.
Homicidal and industrial case histories will be emphasised to illustrate investigative
techniques. It is important to understand that forensic science is multi-disciplinary, and
BIO367 will draw on information covered in previous units, particularly the unit prerequisite.

Prerequisites

BIO247 Biochemistry, BIO270 Biochemistry I or BMS261 Human and Comparative


Biochemistry.

Aims of the unit

The broad aims of this unit are:

1. To provide information on the nature and mode of toxic action of compounds of


forensic importance including plant toxins, heavy metals, chemical warfare agents,
ethanol and drink spikers, medical and illegal drugs, food adulterants and industrial
pollutants.

2. To provide practical training in modern analytical techniques relevant to drug and toxin
determination.

3. To develop scientific reporting skills within a forensic framework.

4. To develop forensic problem-solving skills.

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Learning outcomes for the unit

On successful completion of this unit you should have:

1. Acquired knowledge of the types of toxins involved in homicides, suicides, drug abuse
and industrial accidents.

2. Gained an appreciation of the history of drug and toxin use and abuse.

3. Developed the capacity to illustrate use and abuse with relevant case histories.

4. Gained an understanding of the effects of and mode of toxic action of the major types of
xenobiotics.

5. Acquired an understanding of the biotransformation of xenobiotics and have developed


the capacity to illustrate their metabolic fate with specific examples.

6. Become familiar with and be able to demonstrate technical competence in the analytical
techniques relevant to drug and toxin identification and quantification.

Graduate attributes developed in the unit

This unit will contribute to the development of the following Graduate Attributes:
• Communication
• Critical and creative thinking
• Social interaction
• Independent and lifelong learning
• Ethics
• Interdisciplinarity
• In-depth knowledge of a field of study

This version of the unit was written by Dr Garth Maker, 2015.

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Contact details
Unit Coordinator’s contact details

Name: Dr Garth Maker


Email: G.Maker@murdoch.edu.au
Room: Biological Sciences, Room 3.035
Phone: +61 8 9360 1288

Lecturer contact details

Name: Dr Ian Mullaney


Email: I.Mullaney@murdoch.edu.au
Room: Biological Sciences, Room 2.031
Phone: +61 8 9360 1236

Administrative contact details

If the unit coordinator is unavailable, please contact:

Name: Ms Emma Thorp


Email: E.Thorp@murdoch.edu.au
Room: Biological Sciences, Room 2.002
Phone: +61 8 9360 2939

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How to study this unit
Lecture and workshop classes will discuss the biochemical mechanisms underlying the
molecular toxicology of poisonous compounds. The relevance of these compounds to
forensic investigations will also be discussed.

The laboratory classes in BIO367 will involve applied investigative analysis and will provide
training in the methods used in modern forensic analysis. Each class covers a situation
relevant to human toxicology, and requires you to integrate knowledge of toxicological theory
with sample preparation and instrumental analysis techniques such that by the end of the
class, you should have a clear understanding of the type of toxin under investigation, its
mode of action and its concentration in the contaminated sample analysed.

Contact time

Lectures: 3 hours per week; Laboratory classes: 4 x 3-hour.

Time commitment

As this is a 3 credit point unit, we expect you to spend on average 11 hours per week for the
total weeks of this teaching period (or 150 hours overall) working on this unit.

Attendance requirements

Attendance to laboratory classes is mandatory. Attendance at lectures is highly advisable,


but not compulsory. Videos may be shown which cannot be recorded.

Small group and interactive teaching and learning activities

Laboratory classes in this unit will involve interactive teaching and learning, and an
opportunity for students to work in small groups.

Unit changes in response to student feedback

This unit continually evolves in response to feedback from students. If there are aspects of
the unit that you feel could be modified to improve your learning experience, or could be
covered in greater detail, please inform your Unit Coordinator.

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Resources for this unit
To undertake study in this unit, you will need:

BIO367 Laboratory Manual


This text is available from the Bookshop.

Other references
Mead, R. J. (2013), Introduction to Forensic Toxicology.
This text is provided electronically on LMS. It was written for a previous version of this unit,
but you may still find its contents relevant.

Useful journals (available via Library):


Journal of Forensic Identification
Journal of Forensic Sciences
Journal of Analytical Toxicology

Online resources
National Institute of Forensic Sciences (NIFS)
www.nifs.com.au

Personal protective equipment


Required for laboratory classes: laboratory coat, safety glasses, closed shoes.

The following will be provided during the teaching period:


• Lecture slides
• Lecture recordings
• Workshop handouts

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Study schedule
Lecture timetable

Week Time Topic Presenter


1 Mon 0930 Mechanisms of toxicity Garth Maker
Fri 1430 Toxicokinetics Ian Mullaney

2 Mon 0930 AT: ICP-MS Garth Maker


Fri 1430 Plant toxins Garth Maker

3 Mon 0930 AT: Hair analysis Garth Maker


Fri 1430 Prescription drugs Ian Mullaney

4 Mon 0930 AT: HPLC Garth Maker


Fri 1430 Herbal medicines Garth Maker

NON-TEACHING WEEK

6 Mon 0930 AT: Gas chromatography Garth Maker


Fri 1430 Illicit drugs Ian Mullaney

7 Mon 0930 AT: Mass spectrometry Garth Maker


Fri 1430 Pesticides Garth Maker

8 Mon 0930 No lecture -


Fri 1430 MID-SEMESTER TEST -

NON-TEACHING WEEK

10 Mon 0930 Cosmetic toxicology Garth Maker


Fri 1430 Ethanol/drink spiking Ian Mullaney

11 Mon 0930 Industrial and military toxins Garth Maker


Fri 1430 Adulterants and additives Garth Maker

12 Mon 0930 Heavy metals I Ian Mullaney


Fri 1430 Heavy metals II Ian Mullaney

13 Mon 0930 Systems toxicology Garth Maker


Fri 1430 Modern applications of tox. TBA

14 Mon 0930 No lecture -


Fri 1430 Careers in toxicology Garth Maker

Lecture times and venues


Monday 0930-1030 250.3.106
Friday 1430-1630 260.1.106

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Laboratory timetable

Week Lab Due


1 Lab 1 (Session A) 10-Aug
2 Lab 1 (Session B) 17-Aug
3 Lab 1 (Session C) 24-Aug
4 Lab 2 (Session A) 31-Aug
NON-TEACHING WEEK
6 Lab 2 (Session B) 14-Sep
7 Lab 2 (Session C) 21-Sep
8 Lab 3 (Session A) 28-Sep
NON-TEACHING WEEK
10 Lab 3 (Session B) 12-Oct
11 Lab 3 (Session C) 19-Oct
12 Lab 4 (Session A) 26-Oct
13 Lab 4 (Session B) 2-Nov
14 Lab 4 (Session C) 9-Nov

Lab time and venue:


Labs 1, 2 and 3 Friday 1030-1330 240.2.050
Lab 4 only Friday 1030-1330 245.1.057

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Assessment
Assessment for this unit is conducted in accordance with the Assessment Policy.

Schedule of assessment items

You will be assessed on the basis of:

Assessment item Description Value Due


Dates
Laboratory reports 4 laboratory reports 30% specified
above
Mid-semester test 1-hour test 20% Week 8
Assessment
Examination 2-hour exam 50%
period

Assessment details

Laboratory reports

There are four laboratory classes and each is followed by a short report of approximately 2-3
pages. For each lab class, you are required to present the data generated, along with
answers to the discussion questions posed. This may include an interpretation of the findings
based on the toxicological situation under investigation and consideration of the analytical
technique used, e.g. reproducibility and robustness.

These reports combine your knowledge of toxicology and instrumental analysis to interpret
the data generated and solve the toxicological problem. In total, these reports are worth 30%
of your overall mark, with 7.5% for each report.

Details of the laboratory classes are provided in the Laboratory Manual, which you must
purchase from the Bookshop. Each completed laboratory report should be submitted via the
BIO367 LMS ONE WEEK after your lab class. This means that your report is due the
following Friday by 2355.

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Examination(s)

Mid-semester test (1 hour): Multiple choice test held in a lecture timeslot in Week 8. In
2018, this is Friday 21st September at 1430 in 260.1.106. The test will cover lecture and
workshop material from Weeks 1-7 inclusive. More information will be provided during
semester, and example questions will be made available on LMS to aid your learning.

Final exam (2 hours): Closed book exam to be held in the assessment period at the end of
semester. This exam will consist of short and extended answer questions relating to lecture,
workshop and laboratory material from the entire semester. More information will be provided
during semester, and example questions will be made available on LMS to aid your learning.

Please ensure that you bring identification (i.e. your Murdoch student card) to this exam.
Following the exam period, you can make an appointment with the unit coordinator to view
your marked exam script and discuss any questions you may have.

Assignment submission

All assignments must be submitted via the submission tool on the BIO367 LMS.

Extensions will only be approved (by the Unit Coordinator) for those students with a medical
certificate or extenuating circumstances. Late submission of reports will be penalised at a
rate of 10% per day unless prior approval for the late submission has been obtained.
Deferred assessment is available under extenuating circumstances.

Determination of the final grade

There is no requirement for any particular assessment component to be passed; your grade
in the unit will be determined by the total mark achieved. The pass mark in the unit is 50%
and the mark will be translated to a grade.

See Section 11 in the current Assessment Policy regarding grades.

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What you need to know:

Generic information which students need to know is available at the What you need to know
web page.

The information includes:


• links to the Assessment Policy
• a description of Academic Integrity
• links to information about: Examinations; Non-discriminatory language; Student
appeals; Student complaints; Conscientious objection and assessment policy
• determination of grades from components/marks
• information for equity students"

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Learning guide

For each content lecture of the unit, we have provided specific questions below to guide your
study.

Lecture 1: Mechanisms of toxicity


1. Explain how necrosis differs from apoptosis.
2. What are the three primary causes of necrosis?
3. What are the four key mechanisms by which ATP can be depleted? What is the role
of ion gradients in necrosis?
4. Why are the levels of calcium ions tightly regulated within a cell? What are four
consequences of excitotoxicity?
5. Define the term ‘oxidative stress’. What causes oxidative stress? How can it be
avoided within a cell?
6. What are the cellular consequences of ROS production? List at least six.

Lecture 2: Toxicokinetics
1. Define the term toxicodynamics. How are toxicodynamic effects measured?
2. Which parameters can be measured using a dose-effect (dose response) curve?
3. What is meant by the therapeutic index of a drug? How can this be measured for a
given compound?
4. What values are needed in order to calculate the probability of a risk occurring with
any given compound?
5. Describe the common routes of xenobiotic administration. What is first-pass
metabolism and how can it be avoided?
6. What is bioavailability when applied to a xenobiotic? How can bioavailability be
measured?
7. What is phase I metabolism? How does it differ from phase II metabolism?

Lecture 3: Plant toxins


1. Define the term ‘alkaloid’. What are the two main classes? How are alkaloids
synthesized?
2. Outline the mechanism of action of nicotine. How can this lead to a toxic effect? Be
sure to describe the physiological consequences of nicotine toxicity.
3. Outline the mechanism of action of muscarine. How can this lead to a toxic effect? Be
sure to describe the physiological consequences of muscarine toxicity. How is
atropine used to treat muscarine toxicity?
4. Outline the mechanism of action of strychnine. How can this lead to a toxic effect? Be
sure to describe the physiological consequences of strychnine toxicity.
5. Outline the mechanism of action of cyanide. How can this lead to a toxic effect? Be
sure to describe the physiological consequences of cyanide toxicity.
6. Explain how the mechanism of action of cardiac glycosides allowed them to be
developed into a therapeutic medication.
7. Outline the mechanism of action of ricin. How can this lead to a toxic effect?

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Lecture 4: Prescription drugs
1. Describe the categories in which drugs can affect the developing fetus. Give an
example of each category.
2. Outline the scheduling system used for drug classification in Australia.
3. List the factors that need to be taken into account when prescribing for (a) children,
(b) the elderly and (c) lactating mothers.
4. Describe the adverse effects associated with succinylcholine.
5. How does aspirin exert its anti-inflammatory effects on the body? Describe some of
the symptoms associated with aspirin overdose.
6. Outline the therapeutic effects associated with morphine. Describe some of the
adverse effects associated with morphine overdose. How is a morphine overdose
treated?

Lecture 5: Herbal medicines


1. Explain the four main safety issues associated with herbal medicines.
2. What are the main safety concerns associated with nutritional supplements?
3. Outline the three main safety concerns associated with traditional Chinese medicines.
4. Explain why traditional Japanese medicine (kampo) does not share the same safety
concerns as TCM.
5. What is the main safety concern associated with traditional Indian medicine
(Ayurveda)?
6. Is there any evidence that homeopathic preparations are effective?

Lecture 6: Illicit drugs


1. Outline the mechanism of action of heroin. What are the common adverse effects
associated with heroin use?
2. Describe, with examples of each, the three different classes of cannabinoid. Outline
the physiological and psychological problems associated with cannabinoid abuse.
3. Outline the mechanism of action of cocaine. Describe the adverse effects associated
with the use of crack cocaine.
4. Describe the psychological effects associated with use of LSD.
5. How does MDMA (ecstasy) affect the body?
6. Describe the role of the neurotransmitter substance dopamine in the mechanism of
action of methamphetamine (ICE). Outline the common adverse effects associated
with abuse of this amphetamine.

Lecture 7: Pesticides
1. Outline the mechanism of action of organophosphate pesticides. How can this lead to
a toxic effect? Be sure to describe the physiological consequences of OP toxicity.
2. Outline the primary mechanism of action of organochlorine pesticides. How can this
lead to a toxic effect? Be sure to describe the physiological consequences of OC
toxicity.
3. Outline the mechanism of action of pyrethroid pesticides. Could this lead to a toxic
effect in humans?
4. Outline the mechanism of action of neonicotinoid pesticides. How could this lead to a
toxic effect in humans? What is the major concern with these pesticides?

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5. Outline the mechanism of action of anticoagulant rodenticides. How can this lead to a
toxic effect? Be sure to describe the physiological consequences of such toxicity.
6. Outline the mechanism of action of metal phosphide rodenticides. How can this lead
to a toxic effect? Be sure to describe the physiological consequences of such toxicity.
7. Outline the mechanism of action of hypercalcemic rodenticides. How can this lead to
a toxic effect? Be sure to describe the physiological consequences of such toxicity.
8. Outline the mechanism of action of fluoroacetate. How can this lead to a toxic effect?
Be sure to describe the physiological consequences of such toxicity.
9. Why are the ‘rainbow’ herbicides so notorious?
10. Outline the mechanism of action of paraquat. How can this lead to a toxic effect? Be
sure to describe the physiological consequences of paraquat toxicity.
11. Outline the mechanism of action of glyophosate. Could this lead to a toxic effect in
humans?

Lecture 8: Cosmetic toxicology


To be added once I finish writing the lecture.

Lecture 9: Ethanol and drink spiking


1. What is meant by drug tolerance and drug dependency? How are these connected in
drug addiction?
2. Describe the health problems association with long-term alcohol abuse.
3. What is fetal alcohol syndrome? List the abnormalities associated with this condition.
4. What is the mechanism of action of cantharidin? Other than being an aphrodisiac,
what other clinical effects are attributed to this compound?
5. How do the benzodiazepines exert their action? How are they used therapeutically?

Lecture 10: Industrial and military toxins


1. Outline the mechanism of action of chlorine gas. How can this lead to a toxic effect?
2. Outline the mechanism of action of phosgene gas. How can this lead to a toxic
effect?
3. Outline the mechanism of action of mustard gas. How can this lead to a toxic effect?
4. Outline the mechanism of action of Lewisite gas. How can this lead to a toxic effect?
5. Outline the mechanism of action of nerve gases. How can this lead to a toxic effect?
What are the two broad classes of nerve gas?
6. Outline the mechanism of action of dioxins. What are the three key toxic effects?

Lecture 11: Adulterants and additives


1. Outline the mechanism of action of caffeine. How can this lead to the ‘desired’ effect?
Explain the difference between caffeine dependency and overdose.
2. Briefly outline the potential risks linked to food preservatives and colourings.
3. Briefly outline the potential risks linked to sugar substitutes. What is the molecular
mechanism of ‘sweetness’?
4. What is meant by the term ‘protein substitution’? What is the toxic mechanism of
action of melamine?
5. What is meant by the terms ‘surrogate’ and ‘denatured’ alcohols?
6. Outline the mechanism of action of methanol. What are the two main toxic effects?
Be sure to describe the physiological consequences of methanol toxicity.

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7. What are the two mechanisms of action of thujone?
8. Outline the mechanism of action of ethylene glycol. What are the three main toxic
effects? Be sure to describe the physiological consequences of methanol toxicity.
How does diethylene glycol differ in its effects?

Lecture 12: Heavy metals


1. Describe the various immune responses associated heavy metal exposure.
2. What is chelation and how is it used in the treatment of heavy metal exposure? Name
three chelating agents and their target metals.
3. Outline the mechanism of action of arsenic poisoning. Describe the toxic effects
associated with arsenic poisoning.
4. Describe the toxic effects associated with acute cadmium poisoning. How do they
differ from chronic cadmium poisoning?
5. What are the neurological and behavioural effects of lead poisoning in children?
6. Describe the three chemical forms of mercury associated with poisoning.
7. Outline the mechanism of action of poisoning by hexavalent chromium. What are the
common routes of hexavalent chromium intoxication?
8. Write notes on mechanism of toxicity and common adverse effects of (a) copper, (b)
iron and (c) zinc.

Lecture 13: Systems toxicology


1. What are the major limitations of traditional toxicology?
2. How does systems toxicology differ from traditional toxicology?
3. What are the major current applications of systems toxicology?
4. What are the key techniques used in systems toxicology?
5. What do we do with the data generated by these approaches?

Analytical techniques
AT1: ICP-MS
1. What are the two components that make ICP-MS a hyphenated technique?
2. Explain how the ICP ionization source allows elements to be analysed.
3. Explain how a quadrupole mass analyser functions.
4. Explain the concept of the mass-to-charge ratio (m/z).
5. How are samples typically prepared for ICP-MS analysis?

AT2: Hair analysis


1. Outline the advantages and disadvantages of analysis urine for drugs.
2. What factors affect the incorporation of a drug molecule or metabolite into hair?
3. What are the five basic steps involved in analysis of hair for drugs?
4. Outline the advantages and disadvantages of analysis of hair for drugs.

AT3: HPLC
1. What are the two phases involved in any chromatographic technique? Explain how
HPLC uses these two phases.
2. For what types of sample is HPLC analysis most suited?
3. Explain the difference between reversed-phase and normal-phase chromatography.
4. What is solid phase extraction, and how is it related to HPLC?

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5. What chromatographic parameter do we most commonly use in analysis of HPLC
data?

AT4: Gas chromatography


1. What are the two phases involved in any chromatographic technique? Explain how
GC uses these two phases.
2. For what types of sample is GC analysis most suited?
3. What is the function of the inlet of the GC?
4. What factor is most important in selection of a column for GC analysis?
5. What factor is most important in sample preparation for GC analysis? How does
derivatisation allow this to be achieved?

AT5: Mass spectrometry


1. Explain how the three basic components of a mass spectrometer allow this type of
analysis to be achieved.
2. Explain the concept of the mass-to-charge ratio (m/z).
3. Explain the key differences between the electron and electrospray ionization sources.
4. Explain the terms ‘resolution’ and ‘accuracy’ as related to mass analysers.
5. Briefly explain how quadrupole, triple quadrupole, ion trap and time of flight mass
analysers function.
6. What are the two types of data generated by MS analysis? How does this differ
between hard and soft ionization techniques?

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