Forensic Toxicology Toxicology Study harmful effects of toxins

Forensic Toxicology

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

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.

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

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

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

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

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

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

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

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 >1000 x 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

“Forensic” Alcohol vs. Forensic Clinical

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/100 m. L • Blood glucose 1930; vitreous 1224 mg/100 m. L

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

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

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

Methanol Intoxication? Ø Severe MVA Ø Ethanol not detected, but… Ø Urine Me. OH 530 mg% Ø Liver 190, 300 mg% Ø Spleen 20, 70 mg% Ø Explanation?

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

Carbon Monoxide Deaths Some sources are less obvious…

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

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

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

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

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

Breath Test Instruments • Breathalyzer – Blow 52. 5 ml 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)

Breathalyzer

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

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

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