1. "All substances are poisons: there is none which is not a poison
"All substances are poisons: there is none which is not a poison. The right dose differentiates a poison and a remedy." (Paraclesus, )

2. Do you agree or disagree with this statement? Why or why not?

3. Why does the dose determine if a substance is a poison or a remedy?

4. What does it mean for something to be toxic?

5. Do all substances have the potential of being toxic?

6. Are toxic substances natural or man-made?

7. What do you think toxicology is? What are some toxic substances?

8. Here are some examples of toxic substances…
Rat poison
Alcohol (
Vitamins
Water (

9. Notes Outline Definitions and purpose of postmortem toxicology
Samples of forensic interest
Pitfalls in postmortem toxicology
Interpretation of results
Outline
Definitions and purpose of postmortem tox
What is postmortem forensic toxicology? What are the boundaries of postmortem forensic toxicology and the role of the toxicologist in postmortem cases?
Samples of Forensic Interest
What samples are the most relevant to the forensic toxicologist?
Handling and storage of samples
How should postmortem forensic toxicology samples be stored and handled? And why should we care about how postmortem forensic toxicology samples are stored and handled?
Pitfalls in postmortem toxicology
What are some of the most common problems in postmortem forensic toxicology? How do factors such as putrefaction, decomposition and redistribution of drugs after death affect the ability of the forensic toxicologist to draw conclusions?
Interpretation of results
What are the limitations of the toxicologist in reporting results from postmortem blood samples? What are some of the interesting pieces of information that the toxicologist is able to give to the pathologist in order to help them determine cause and circumstances of death - as examples - discuss acute v. chronic ingestion of drugs and identify pathological changes that occur following drug overdose.

10. Postmortem Forensic Toxicology
The analysis of samples collected during an autopsy for drugs or poisons.
How might one define postmortem forensic toxicology?
In terms of purpose:
The purpose of postmortem forensic toxicology is to perform qualitative and quantitative analysis for drugs and their metabolites, and poisons such as metals, carbon monoxide, and volatile substances in human fluids and tissues collected after death.
The postmortem forensic toxicologist will then evaluate the role of drugs or poisons as either determining factors or contributory factors in the death of the individual. This includes interpretation as to what the physiological effect at time of death might have been (e.g. acute toxicity such as respiratory depression) and/or what the behavioural effect at the time of death may have been (e.g. impairment leading to drowning, motor vehicle collision or other traumatic cause of death).

11. What Can The Determine?
The presence or absence of a drug or poison in a submitted sample
The amount of drug or poison that is present in the submitted sample
Two important definitions - qualitative versus quantitative analysis.
Qualitative analysis simply determines the presence or absence of a drug or poison in a submitted sample, basically answering the question – was this person exposed to a drug or poison?
Quantitative analysis actually determines the amount of drug or poison that is present in the sample. In other words, you are determining the quantity of drug that is present – this is a memory tool to remember the difference between quantitative and qualitative analysis (determining quantity is quantitative analysis).
Quantitative analysis is always preferable as it is difficult to make a meaningful interpretation based solely on the presence or absence of a drug or poison. However, in some situations qualitative analysis may be all that is meaningful due to the nature of the submitted sample, or qualitative analysis may be a useful starting point in order to direct further work. For example, many initial drug screens are qualitative in their analysis; it is the confirmatory method that is quantitative in its nature.

12. Some Examples Types of cases: Suspected drug intoxication cases
Fire deaths
Homicides
Driver and pilot fatalities
Therapeutic drug monitoring
Sudden infant death (SIDS)
These are the types of cases that typically fall into the realm of postmortem forensic toxicology.
Unexplained deaths, with no apparent cause (often suspected to be drug intoxication cases) as well as those that are strongly suspected of being drug intoxication cases.
Fire deaths – measurment of toxic gases such as carbon monoxide and cyanide which may be inhaled during a fire. Furthermore, drugs may be implicated as having incapacitated a victim, thereby preventing their escape from a fire.
Homicides – homicidal poisonings themselves, are rare – but many homicide cases are related to drug use and drug abuse.
Driver and pilot fatalities – where drug impairment may help determine the cause of a crash. Other traumatic causes of death will also require postmortem toxicology analysis (such as drownings, falls)
Therapeutic drug monitoring – for example, determining whether an individual with a seizure disorder has been compliant in their medication use.
SIDS – by definition, SIDS is a diagnosis of exclusion. Therefore, toxicology must be comprehensive in these case to rule out any other cause of death.

13. Samples of Forensic Interest

14. Typical autopsy specimens
Blood
Urine
Stomach contents
Bile
Liver
Hair
Vitreous humor: the transparent jellylike tissue filling the eyeball.

15. Blood Antemortem  ideal blood sample
Postmortem blood is not truly “blood”
Anatomical site of collection at autopsy should be noted
The best possible blood sample, even in postmortem forensic toxicology is an antemortem blood sample. In the case of postmortem forensic toxicology, this antemortem blood sample would ideally be a blood sample that is collected just prior to the expiration of the patient. Occasionally these samples are available - for example, in cases where the deceased was rushed to hospital and where blood was collected in the hospital emergency room.
What we are usually faced with, however, is an analysis in postmortem blood samples. Something to keep in mind is that postmortem blood is not truly blood. It may look like blood - but in fact it is not - it is a fluid, from the vasculature that is collected after death. Postmortem blood however has already begun to break down and hemolyze and is not the same as an antemortem blood sample.
As will become clear through discussions of the limitations and pitfalls of postmortem forensic toxicology, the anatomical site of collection at autopsy should be noted and MUST be accurate (for an appropriate interpretation of the blood drug concentrations).
Example: “heart blood” collected from a patient who was an organ donor and whose heart was taken for transplantation purposes in hospital.

16. Hematoma Hematoma: a solid swelling of clotted blood in the tissues
Protected from decomposition for a while
Analysis will indicate what drugs were present in the blood at the time of the hematoma was formed

17. The man had been drinking prior to receiving the head trauma.
Hematoma case example
A 26 year old man was found dead at the bottom of a staircase. Death was due to physical injuries.
Question as to alcohol use prior to fall down stairs
No urine available at autopsy
Alcohol not detected in femoral blood (from the leg)
Alcohol in hematoma blood  150 mg/100 mL
For example…
These results indicate that the deceased had been drinking prior to receiving the head trauma. Since ethanol is detected in the hematoma, but not in the femoral blood, you can also conclude that this individual survived for a substantial period of time AFTER receiving the head trauma but BEFORE death occurred. In the case of alcohol, the rate of elimination of alcohol from the blood is very well know and I can predict that this individual would have had to survive between 7 and 15 hours after hematoma formation in order to clear the femoral blood of alcohol.
Caution: Hematomas may not form immediately upon receiving an injury. Therefore this hematoma alcohol concentration will not necessarily indicate the BAC at the time of the accident….more appropriate to state the hematoma alcohol concentratoin indicates the BAC at the time of hematoma formation.
The man had been drinking prior to receiving the head trauma.

18. Produced by the kidneys Blood filtered by the kidneys to remove toxins
Urine
Produced by the kidneys
Blood filtered by the kidneys to remove toxins
Stored in the bladder
Drug in the urine indicates that some time before death the drug or poison was present in the blood of the victim.
Urine is produced by the kidneys as a result of blood filtration. Along with other wastes, drugs and their metabolites are filtered by the kidneys and are contained in urine. Urine, is stored in the bladder until voided. It may sound weird to think of it his way – but urine, since it is stored in the bladder is actually “outside of the body” – and it is no longer subjected to metabolism.
Since urine is stored for a period of time before it is expelled, the presence of a drug in the urine does not necessarily mean the drug was present in the blood at the time of death. It simply means that some time prior to death the drug or poison was present in the blood.
In this way, urine analysis – in isolation of blood analysis is of limited value.

19. Stomach contents
Drugs that have been orally ingested may be detected in stomach contents
Caution: drugs administered by other routes may also diffuse into stomach contents from the blood
A portion of the stomach contents are typically collected at autopsy. Stomach contents may contain unabsorbed poisons, tablets, capsules, caplets which may be intact and visible. These can be removed from the stomach contents, photographed, and identified.
Drugs in the stomach contents do not necessarily indicate oral ingestion!
Many weak bases are subject to secretion into the gastric contents due to the pH gradient between plasma and the stomach. Ion trapping in the stomach produces very high concentrations of these agents, even after intravenous or other non-oral routes of administration. Thus the finding of even appreciable amounts of a basic drug in the gastric contents is not a reliable indication of oral ingestion.
Can you quantify stomach contents to determine if a person has taken a drug overdose?
Stomach contents are not homogenous in their nature.
Correct procedure of collecting stomach contents is for the pathologist to ligate the stomach, remove it from the body, remove all stomach contents, mix thoroughly and provide a small quantity to the toxicology lab – again – this is rarely, if ever, done.
If stomach contents were collected properly, quantitation may be valid and may be useful…however, in light of the fact that stomach contents are typically a scooped, non-homogenous sample, it is not acceptable practice to quantify the contents and make any valid interpretation from the results.

20. Case Example A 26 year old woman is found dead in bed
Many medications in her home:
Amitriptyline, Oxycodone, Morphine, Paroxetine, Diphenhydramine, Pseudoephedrine, Phenobarbital, Codeine, Temazepam, Diazepam
Only 3 mL of blood collected at autopsy
Analysis of stomach contents:
Amitriptyline: detected
Nortriptyline: detected
Point out that 3 mL of blood is not a lot of blood for analyses – in fact, probably only enough blood to perform one or two quantitative analyses.

21. Hair
Metabolism does not occur in hair. So if it is there, it stays there.
Can provide a historical record of drug or poison exposure
Hair analysis – has, in recent years, become a new interest in postmortem forensic toxicology. Drugs and poisons are stable in hair – that is, they are not subject to metabolism or other non-enzymatic degradation.
Since hair grows at a predictable rate (generally 1 cm/month) – hair can be used to provide a historical record of drug or poison exposure. Procedure is to chop a hair sample into 1 cm increments and analyze them separately to “track” drug exposure over a long period of time (as long as the hair will allow, basically).
Pros and cons of hair analysis are still being uncovered – for example there have been studies that have shown racial variability in the binding of drugs to hair. It is a developing area of research in forensics right now [not something that we at the CFS do]

22. Case Example 30 year old woman, previously in good health
Nausea, vomiting, diarrhea, rash, fever
Weakness in hands and feet
Hospitalized for seizures
Hair analysis for arsenic showed chronic arsenic poisoning over 8 month period
A case of homicide by chronic arsenic poisoning. The victim was a 30 year old mother of two who was in excellent health until 8 months prior to her death when she developed an apparent viral syndrome characterized by persistent nausea, vomiting and diarrhea with low grade fever and rash. Within 2 weeks she developed a symmetrical parasthesia and weakness in both her hands and feet. These symptoms progressed and resulted in a diagnosis of Guillian Barre syndrome. During the following 2 months she had several episodes of severe g.I. distress. Two weeks prior to her death she was hospitalized for mental confusion, hypotension and seizures. Her condition improved until she had dinner with her husband after which she developed severe gastrointestinal distress. Her condition then gradually deteriorated until death.
A misplaced laboratory result found after her death indicated an arsenic concentration of 2.1 mg/100 mL.

23. The end

24. Case Studies Assignment
With your partner, read the case studies.
Use your Chromebook to figure out what the toxic substance is.
Assign two cases to each partner and research the toxic substance to answer the questions.