Forensic toxicology

Toxon (greek) – a bow What is forensic toxicology? Forensic toxicology is a discipline of forensic sciences concerned with the study of thousands of toxic substances or poisons and application this knowledge to the purposes of the law. Toxicology encompasses theoretical considerations, methods and procedures from many disciplines including analytical chemistry, biochemistry, epidemiology, pharmacodynamics, pathology, and physiology. Toxicology the study of the toxic or harmful effects of chemicals action of toxic substances occurrence of their harmful effects the symptoms and the treatment of poisoning analysis: identification of the substances, quantitative determination "All substances are poisons: there is none to be not a poison. The right dose differentiates a poison and a remedy" Is not fixed for every drug or poison – different people have a wide range of sensitivity or resistance, and it may vary from time to time for the same person LD50 is determined in experiments on particular species of animals, so this cannot be simply It’s practically impossible to „calculate back” from a blood concentration of a drug the dose that had been used and when What are the substances commonly detected and determined at biological samples in cases of poisoning? The list is not closed and is continuously verified and modified benzodiazepines zolpidem, zopiclone barbiturates TCA – amitriptiline, imipramine, desipramine, clomipramine, doxepine SSRI – fluoxetine, paroxetine, fluvoxamine, sertraline, citalopram SNRI – wenlafaxine IMAO – moclobemide other – mirtazapine, mianserine, trazodone phenotiazines (chlorpromazine, promazine, perazine, methotrimeprazine, perphenazine, thioxanthenes (chlorprothixene, fluenthixol, zuclopenthixol) butyrophenones (haloperidol, droperidol) benzamides (sulpiride) atypical (clozapine, olanzapine, risperidone, quetiapine) β-antagonists - metoprolol, acebutolol, propranolol Ca-channel blockers - diltiazem, verapamil ACE – enalapril, trandolapril, perindopril antiarrythmics – propafenone glycosides – digoxine, digitoxine diuretics – indapamide, hydrohlorothiazide other – trimetazidine opiates (morphine, codeine, heroine, oxycodone, buprenorphine) synthetic (tramadol, pethidine, pentazocine, methadone, phentanyls, propoxyphene) amphetamine, methamphetamine designer drugs – MDMA, MDA, MDEA, PMA, PMMA and many others LSD-25 psilocin, psilocybin mescaline salvinarine (Salvia divinorum) cannabinoids GHB (γ-hydroxybutyric acid – analogue of GABA, acting like alcohol, popular „date rape phosphoroorganics (very toxic, inhibitors of acetylcholinoesterase) carbamates chlorinated hydrocarbons triazines phenylacetic acids derivatives pyretroides other substitution for ethanol, fixed (non-volatile), of sweet-hot taste, available – component of the coolant liquid, onset of intoxication – similar to ethanol abuse toxic metabolites, causing excessive acidosis: glycol aldehyde, glyoxalic acid, glycolic acid (level of acidosis - prognosis as for life, not for the blood concentration of glycol), lesion of kidneys – deposition of calcium oxalate crystals (late metabolite) – oliguria, anuria the faster diagnosis – the better prognosis as to life (hemodialysis) colorless and odorless gas more light than air very penetrating incomplete combustion (cookers, heaters, etc., insufficient ventilation, chimney obstruction) car exhaust (4-8% CO) leakage from containers (ex. laboratory cylinders) fire (CO toxicity is related to cyanide and hypoxia) displacement of oxygen from hemoglobin 200-300 times higher affinity than oxygen very stable binding Headache, nausea, drunk-similar symptoms, coma Survivors: cystic degeneration of basal ganglia Cardio-respiratory failure (kind of blood poison) Cherry pink color of the lividity, intensively red color of the blood and tissues Quick – spectroscopy (very simple, but of low sensitivity method) Hospitals Spectrophotometry (e.g. Wolff’s method, Fretwurst-Meineck’s method) Gas chromatography (CO is converted and detected as methane) Normal level (non-smokers) < 4% Smokers ≤10% Symptomps of toxicity ~20-30% (headache, dizziness, nausea) Loss of consciousness 40-50% death 50-60% Post-mortem changes suggesting poisoning remains of plants, mushrooms, tablets, capsules atypical color or/and smell (chemicals agents) gastritis with oesophagitis (irritative agents) fatty changes, cirrhosis, necrosis (toxins of Amanita phalloidea, heavy metals, arsenic, Cl- derivatives of organic solvents, acetaminophen, NSAID) Necrosis, inflammation (mercury, chromium, ethylene glycol) solutions of cyanide salts of sodium and potassium have high pH value (11-12), and it is very irritable for gastric mucosa 10-15 ml It is better to collect a small but full bottle than a large bottle filled in half urine vitreous body stomach with contents part of liver with gall bladder one kidney piece of brain piece of lung Lung and brain are important when volatile organic compounds are suspected in some cases Skin with underlying tissues – intramuscular or subcutaneous injections Nails and hair suspicion of chronic poisonings - arsenic, thallium, antimony, mercury (hair must be orientated in one direction and root must be determined) control of abstinence from drugs anti-doping tests suspicion of exposure on GHB (rapes) Similar to routine autopsy if not decomposed tissues from abdomen cavity skeleton muscles warning: embalming fluids may contain: formaldehyde, methanol, iodide compounds samples should be collected in glass, chemically clean tightly closed containers (jars, vials) all containers should be described name of deceased date of autopsy name of the sample addition of any preservatives is forbidden samples should be refrigerated or (better) frozen by diffusion mean time of absorption after single bolus of alcohol: 30-90 min. the gastric mucosa contains alcohol dehydrogenize which partly decomposes alcohol before it is absorbed into the blood stream The effects of alcohol intoxication Methods of alcohol analysis in biological samples Simple, cheap Linear in the range of 0-5 promiles Unspecific (false positive due to other reducing agents: H2S, mercaptans, other alcohols, aldehydes etc) Enzymatic ADH EtOH +NAD EtCHO (acetaldehyde) +NADH Volume is not weight! 1 ml EtOH = 0,79 g EtOH 40% v/v whisky/vodka
13% v/v wine
5,7% v/v beer
0,79 g/ml x 5,7 ml = 4,5 g EtOH/100ml Rate of elimination (metabolism) β60 0,1 – 0,2 ‰ per hour may be slower or faster (up to 0,6 ‰ per hour in rare cases) may be different for the same person

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