1. Forensic Toxicology

2. Toxicology Study harmful effects of toxins on animals and plants Many different types: Environmental (air, water, soil) “Consumer” (foods, pharmaceuticals, cosmetics) Medical, clinical, forensic

3. Clinical vs. Forensic Toxicology Clinical: –emergency screening (e.g. overdose) –therapeutic drug monitoring (TDM) (limited menu of drugs) Testing only done if likely to affect the management and course of clinical treatment.

4. Forensic Toxicology Broad based screening and measurement for legal purpose –Postmortem (ME/Coroner) –Criminal (MVA; assault) –Workplace drug testing –Sports (human & animal)

5. What Do Forensic Toxicologists Do? Analyze blood and other human fluids or tissues for alcohol, drugs and poisons (analytical toxicology) Interpret analytical results Considerable experience required

6. Analytical Toxicology: What do you need? Strong Chemistry background –Analytical, organic, physical Accuracy and attention to detail Computer skills Troubleshooting skills Willingness to do repetitive work A “strong stomach” Common sense, patience

7. Why? Cause of death? Contribution to death? Cause Impairment? Explain Behavior? Footnote: Drug or alcohol caused deaths almost never show specific signs at autopsy.

8. How? Immunoassay TLC GC HPLC GC/MS LC/MS (AA; ICP-MS)

9. Analytical Basis of Toxicology Immunoassay – 10% Chromatography – 85% Other – 5% Separation, detection, identification and measurement of drugs in biological specimens

10. The Analytical Process Sample receipt –Chain-of-custody Review request and information Decide on testing to be performed Analytical testing Review, evaluate and interpret results

11. What are the (Analytical) Problems? 1.Endogenous substances cholesterol, fats, proteins putrefactive amines 2.Enormous range of drug concentrations therapeutic concentrations range over at least 100,000 fold can vary >1000x even for single class of drugs 3.Some drugs cannot be readily detected Analytical conditions may not be appropriate Drug/poison may be new or very unusual

12. “Forensic” Alcohol vs. ForensicClinical

13. Intoxication? A young man appeared intoxicated on a trans- Canada Greyhound bus Police met the bus; escorted the man to hospital at 2.30 am Examined; released to police & placed in cells to “sober-up” Found with agonal breathing 7 am; died shortly after Blood alcohol “0”; acetone 170 mg/100mL Blood glucose 1930; vitreous 1224 mg/100mL

14. Postmortem Fermentation Blood ON ITS OWN is UNRELIABLE as a specimen for assessing the presence of alcohol at the time of death. Blood Vitreous

15. Postmortem Fermentation 86 y.o. lady died suddenly from heart disease; autopsy ordered and blood taken for routine toxicology Blood alcohol 320 mg/100 ml –Urine 0; bile 20 mg/100 ml No evidence of alcohol abuse No alcohol in morgue Meds in blood and urine correlated –Warfarin & digoxin; also blood typing

16. Methanol Cases… Methanol causes: blindness, acidosis, hypoxic brain damage and death

17. Methanol Intoxication?  Severe MVA  Ethanol not detected, but…  Urine MeOH 530 mg%  Liver 190, 300 mg%  Spleen 20, 70 mg%  Explanation?

18. Carbon Monoxide Deaths Some are obvious… Carbon monoxide binds to hemoglobin 200x stronger than oxygen!

19. Carbon Monoxide Deaths Some sources are less obvious…

20. Postmortem Redistribution  False Premise Blood levels of drugs after autopsy reflect those at the time of death  Reality Many drug levels increase after death; some 2–10 fold Many mechanisms Some drug levels decrease after death (e.g. cocaine)

21. Other Interpretation Issues Combined Drug Deaths –additive or synergistic toxicity Tolerance – need to increase dose for same effect Genetically Impaired Metabolism – 7-10% Caucasians are slow metabolizers Drug-Drug Interactions –can cause synergistic or fatal toxicity

22. Other Interpretation Issues Drug Accumulation –caused by decreased metabolism or clearance Medical Artifacts –intravenous lines; incomplete distribution Delayed deaths –drug toxicity causes physiological damage; drugs levels may fall to near zero before death occurs

23. Alcohol Specifics (Route) Alcohol in stomach (20% absorbed) and intestine Absorbed within minutes into bloodstream –Timing affected by: –Time taken to consume drink –Alcohol content –Amount consumed –Stomach contents

24. Alcohol Specifics (Route) Alcohol distributed to watery parts of body via blood Liver, 1 st stop- Begin detoxification (0.015% w/v per hour Heart Lungs-Alcohol vapors out with breath –Using Henry’s Law can relate amount of alcohol in breath to amount in blood Brain-impair neuron transmission

25. Breath Test Instruments Breathalyzer –Blow 52.5ml of alveolar air into machine –Added to potassium dichromate, silver nitrate, sulfuric acid and water –Alcohol converts dichromate to acetic acid –Dichromate amount reduced-measured via a spectrophotometer in machine (must be calibrated! and chemicals pure)

26. Breathalyzer

27. Alcohol and NYS Law 0 Tolerance Law –Less than 21 –Drive after drinking –Blood alcohol.02-.07 violation of DWAI –Suspend license –Fine –Increased insurance rate –jail

28. Alcohol and NYS Law Everyone else: –DWAI at.08 blood alcohol level –1 st Offence=15 days jail, $300-500 fine, 90 day license and registration suspension, surcharge, victim panel –2 nd Offence=30 days, $500-750 fine, 6 month license and registration suspension, surcharge, victim panel –Future=Felony

29. What’s your blood alcohol level? http://www.ou.edu/oupd/bac.htm