Introduction to Forensic Toxicology

1. Introduction to Forensic Toxicology John P. Wetstein Toxicology Training Coordinator Illinois State Police Division of Forensic Services Forensic Sciences Command

2. Role of Forensic Toxicologist • To provide Quality analysis • Complete • Accurate • Timely • To provide interpretation of results • To testify effectively • To assist the trier of fact in understanding

3. Toxicology Testing • Different from clinical toxicology • Instrumentation overlap • Redundancy is increased • Speed is decreased • “Cheap, Good, or Fast – pick two”

4. Forensic Toxicology • Results are developed with the needs of the legal community in mind • Requires “second test “ philosophy • Two tests based on a different chemical principle • One test more sensitive than the other

5. Pharmacology • Pharmacokinetics – how the drug moves through the body • Absorption • Distribution • Metabolism • Elimination “What the body does to the drug”

6. Pharmacology • Pharmacodynamics • How the drug interacts with receptors in the brain • What are the effects? • How long does it last? “What the drug does to the body”

7. Ethanol Absorption • Dermal • Requires open abrasion or lesion • Elimination is faster than absorption for intact skin • Mucosal Membranes • Oral, vaginal, and rectal • Oral ingestion

8. Ethanol in the stomach • Only 25% of a dose is absorbed in the stomach • Ethanol is a secretagogue • More ethanol = more secretions= better barrier • 30% solution for maximal absorption • Retention in the stomach will delay absorption • At low concentration Michaelis-Menton kinetics apply

9. Ethanol in Small Intestine • Most absorption takes place here • Small intestine has roughly 300 square meters of surface area (over 3200 square feet!) • Colon can absorb ethanol – it usually never gets the chance

10. Volume of Distribution • Widmark derived the formula • BAC = A/rp • Where A is the alcohol dose • R is the volume of distribution • P is the body weight • Widmark calculated r to be .68 for males and .55 for females • Later researchers found an average of .70 and .60

11. Algebra Refresher

13. Widmark Simplified r varies by individual but for males it is 0.7 and 0.6 for females

14. Using Volume of Distribution • Two significant elements can be derived • The alcohol dose • The estimated BAC • Example – How many grams of ethanol would be required to bring BAC up to .08 g/dL given a 220 lb. male? ?

15. Estimating Dose Required • Knowns: • Mass = 100 kg • Volume of distribution = .70 • BAC = .08 g/dL (or .8 g/kg) • Unknown = x grams ethanol

16. Algebra • 0.7 = wbc/.08 g/dL • wbc = .08 g/dL x 0.7 • wbc = .056 g/dL = .56 g/kg • 0.56 g/kg x 100 kg = 56 grams of ethanol • One drink = 11 grams ethanol

17. Estimating a BAC • Knowns • Mass = 55 kg (120 lbs) • Ethanol dose = 5 glasses of wine • Volume of distribution = .60 • Unknown • BAC

18. Estimating BAC • 0.6 = wbc / bac • 0.6 = (55 grams etoh / 55 kg ) / bac • bac = (1 g/kg ) /0.6 • bac = 0.1 g /dL / 0.6 • bac = .167 g / dL

19. Units for the Equation • WBC must be expressed as grams/kilogram • Later converted to grams/dL • 1 dL weighs 0.1 kilogram • BAC must be expressed as grams/dL • Must convert body weight to kilograms • 1 lb = .45 kg 1kg = 2.2 lb • Must know how many grams of ethanol in a standard drink. • Generally 11 grams

20. Mary weighs 165 lbs. What is her mass in kilograms? She drinks four shots of whiskey. How many grams of ethanol is that? What is her “Whole Body Concentration?” What is her Rho or Volume of Distribution? What is her maximum theoretical BAC Practice Problem

21. Ethanol Elimination • 95% of ingested ethanol is eliminated in the liver. • Dubowski reported these average rates in 1976 • .015 g/dL/hour for males, .018g/dL/hour for females • Both exhibited ranges of .011 - .022 • Shajani and Dinn (1985) • .018 for males, .020 for females • Same ranges applied

22. Taken from Medicolegal Aspects of Alcohol Determinations in Biological Specimens by James Garriot, PhD.

23. Retrograde Extrapolation • At most alcohol concentrations, ethanol is eliminated at a steady state. • Given a known alcohol concentration, one can estimate a BAC at a previous point in time • Example: Driver at .070 g/dL measured 2 hours after an accident. What was BAC at the time?

24. Illustrative Question • If I drove 65 miles / hour for 2 hours, how far have I gone? • (2 hours) (65 miles/hour) = 130 miles • If all of my driving has been northbound on Interstate 55, and I stopped at the 235 mile marker, where did I start driving ? • 235 miles – (2 hours) (65 miles/hour) • 235 – 135 = 100

25. Retrograde Extrapolation • Assumptions: • The driver is post absorptive at the times in question • 45 min to 2 hours after last drink – clinical • Within 15 minutes in social situations • The driver is in a “normal” state of health and metabolizes within normal ranges • Normal ranges I use are .010 to .020 • Alcoholics/chronic abusers .030 +/- .009

26. Retrograde Extrapolation • Driver drinks at a bar and leaves at 12:30 am. At 1:15, he is involved in a crash. At 3:00 am, blood is drawn for alcohol testing. The BAC is measured at .072 g/dL. • What was the estimated BAC at 1:15?

27. Retrograde Extrapolation • Low estimate: .072 + (1.75 hours * .010 g/dL/Hour) = .072 + .0175 = .089 High Estimate: .072 + (1.75 * .020 g/dL/hour) = .072 + .035 = .107

28. People vs Floyd • Defense won appeal • Expert assumed too many factors away • Factors listed irrelevant to metabolism • Factors never known • Not a bright line ruling against back extrapolation • Foundation question should address factors

29. DUI Kit Swabs • Contaminated swab defense • Ethanol and Isopropanol were detected in the iodine solution included in DUI kit • Concentrations were .005 g/dL • Factors to remember: • This can not increase a BAC of forensic significance – even in a worse case scenario • Both volatiles are present in equal amounts and both are readily detectable • Contamination would be evident by IPA peak

30. DUI Kit Swabs • Venipuncture requires drying of the site prior to needle insertion • Dubowski demonstrated contamination with wet ethanol sponge • Placed directly on site • Needle under vacuum • Defense will provide multiple references • These are legal, not scientific concerns

31. DUI Kit Swabs • Prior administrative rule stated “…does not contain alcohol” • Amended by emergency change in 2007 – later made permanent • Manufacturer is unable to detect this trace level • Source of the contamination is unknown

32. Drug Pharmacokinetics • Absorption • Route of administration • Oral, inhalation, intravenous, intranasal, intramuscular, transdermal • Route effects the rapidity of onset • Blood-Brain barrier • Crack vs cocaine hydrochloride

33. Drug Pharmacokinetics • Absorption • In order for the drug to exert action, the drug must be absorbed into the bloodstream and move through membranes to get to the appropriate receptor • Absorption is largely dictated by the chemical properties of the drug itself

34. Drug Pharmacokinetics • Distribution • Governed largely by solubility • Hydrophobic – into fats and tissues (THC) • Hydrophillic – into body water • Half Life is a function of solubility • Half-Life is time taken to remove half of the concentration • Hydrophillic substances are excreted quickly

35. Pharmacokinetics • Metabolism • Can go from active to inactive • THC to THC-COOH • Cocaine to benzoylecgonine • Can go from inactive to active • Codeine to morphine • Carisoprodal to meprobamate

36. Pharmacokinetics • Elimination Process of removing the drug and or metabolites from the body. Usually by making the substance more polar and water soluble. Zero Order Kinetics – steady (ethanol) First Order Kinetics – not linear; uses half lives

37. Pharmacokinetics

38. Pharmacokinetics • With anything other than linear elimination, it is generally not possible to back extrapolate • Baseball • Maple Leaf

39. With the exception of ethanol, there is so far no widely accepted correlation between the drug concentration in blood and a corresponding level of driving impairment among the scientific community. What is more, factors such as tolerance can have a profound effect on the pharmacodynamic response in an individual. Sarah Kerrigan, PhD Drug Toxicology for Prosecutors American Prosecutors Research Institute

40. Driving and Impairment • Drugs can introduce impairment in the following ways • Coordination • Judgment / Decision Making • Perception • Tracking • Reaction Time • Divided Attention / Multi-Tasking

41. Driving and Impaiment • Coordination • Have to put hand and foot movements together at appropriate times to effectively control the car • Drugs effect nerves and muscles • Once a decision is made to put input into the vehicle, the body needs to respond at the right time and to the appropriate degree

42. Driving and Impairment • Judgment and Decision Making • Driving requires the ability to concentrate and assess risk appropriately • Stimulants may give a false sense of invincibility and induce riskier behavior

43. Driving and Impairment • Perception • Visual acumen can be diminished • Blurred vision • Ability to accurately determine distances and subtle changes in texture • Tracking • Required to maintain vehicle position on the roadway • May manifest in weaving

44. Driving and Impairment • Divided Attention and Multi-Tasking • Multiple visual cues that demand attention • Road signs, other cars, pedestrians, changes in road surface • Multiple activities that require attention • Gas, brake, steering input • Depressant drugs retard ability • Stimulant drugs may cause hypervigilance

45. Interpretation Issues • What does it mean? • A toxicology result by itself will not normally be sufficient to make a statement about impairment • A toxicologist can testify to the expected or anticipated effect of a particular drug • Can not state with complete certainty that all drivers would be impaired given a drug and/or concentration

46. Interpretation Issues • How long can it be detected? • Detection time • Dose • Route of administration • Elimination Rate • Presence in urine may not be reliable indicator of recent usage • Metabolism from blood can be very rapid

47. Drug Classes (functional) • Stimulants • Amphetamines, cocaine, MDMA • Depressants • Benzodiazepines, barbiturates, anti-convulsants, sleep inducers • Opiates • Oxy, Hydrocodone, codeine, morphine, Heroin • Hallucinogens • GHB, THC, LSD • Serotonin re-uptake inhibitors (SSRIs) • Prozac, paxil, lexapro, zoloft

48. Typical Tests • Immunoassays • Lack specificity • React to classes of drugs • Cocaine, THC, Amphetamines, Barbiturates, Benzodiazepines, PCP, Opiates • Individual drugs within class behave differently • Alprazolam vs Lorazepam • Can be used on blood or urine

50. Step 1 – Placing the plates in place. Antibodies are for the drug/metabolite in question. Plates can accept multiple assays, but the plate has to be programmed correctly on the instrument.