Forensic Toxicology Lecture Notes 2020 PDF

. 2020 Forensic Toxicology Lecture 10 By Dr. Ghada Samy 12/4/2020 1  The history of Forensic Medicine Imhotep (B.C.) is considered as the first medico-legal expert....

. 2020 Forensic Toxicology Lecture 10 By Dr. Ghada Samy 12/4/2020 1  The history of Forensic Medicine Imhotep (B.C.) is considered as the first medico-legal expert. He was the personal physician & Chief Justice to the King of Egypt. Paracelsus defined a poison for the first time. He wrote: ‘‘all substances are poisons: there is none which is not a poison. The right dose differentiates a poison and a remedy.’’ Forensic toxicology Forensic toxicology involves the use of toxicology for the purposes of the law. It is considered a hybrid of analytical chemistry & fundamental toxicology. It includes a wide range of applications such as: 1. Occupational toxicology 2. Urine testing to detect drug use or misuse or abuse 3. Analysis & identification of any chemical that may cause death or injury to humans or properties Examples: Presence of ethanol in drivers’ blood in car accidents. Carbon monoxide concentration in fire victims. Degree of carbon monoxide saturation of the blood may indicate whether the deceased died as a result of fire or was dead before the fire started. Illicit psychoactive drugs often play significant role in circumstances associated with sudden or violent death. Negative toxicological finding can cause death, e.g; a person with a seizure disorder didn’t take prescribed medication & that caused death 2  4. Provides valuable epidemiological & statistical data Examples: Forensic toxicologists are the first to alert community to new epidemics of substance abuse & dangers of abusing OTC drugs. They determine chemical identity & toxicity of novel analogs of psychoactive agents, such as in case of ecstasy (a methamphetamine derivative [MDMA]). 5. Courtroom testimony & consultation concerning toxicoses Forensic toxicologist is often called upon to testify in legal proceedings to provide reports that may be introduced as evidence in a court of law. Objective testimony by a toxicologist usually involves a description of his/her analytical methods & findings and any associated opinions Postmortem toxicology Autopsy refers to the systematic examination of a dead person for medical, legal and/or scientific purposes. Types of postmortem toxicology: 1. Academic: Dissection carried by students of anatomy 2. Pathological, hospital or clinical: Done by pathologists to diagnose cause of death or to confirm a diagnosis. Physicians cannot order these autopsies without the consent signed by one's family & relations 3. Medico-legal: Type of scientific examination of a dead body carried out under the laws of the Country for protection of rights of citizens. The basic purpose of this autopsy is to establish cause & manner of death. In every case, autopsy must be complete; all body cavities should be opened & every organ must be examined. Partial autopsies have no place in forensic pathologic practice 3  Investigation of toxicity-related death It may be divided into three steps: (1) The case history and suitable specimens (2) Toxicological analyses (3) Interpretation of the analytical findings (1) The case history and suitable specimens The toxicologist should collect these information about the decent: Age, sex, weight, medical history & occupation of the decedent as well as any treatment administered before death, the gross autopsy findings, the interval between the onset of symptoms & death & the time of death Fluids and tissues should be collected before embalming  The embalming process will dilute or chemically alter the poisons present, making it either difficult or impossible to be detected  Methyl or ethyl alcohol may be a constituent of embalming fluid, thereby affecting interpretation of the analytical findings. Specimens of many different body fluids & organs are necessary, as drugs & poisons display varying affinities for body tissues. 4  Toxicological analysis is often requested for cases of burned, exhumed, putrefied, & skeletal remains. Therefore, Nontraditional specimens could be collected: 1. Vitreous humor of eye: Important as it is protected from putrefaction, charring & trauma. It is used for determining postmortem interval (PMI) & detection of most drugs, anions & volatile poisons, as: alcohols, ketones & glycols 2. Hair analysis: Measure individual exposure to heavy metals, as: arsenic, mercury & lead 3. Bone marrow 4. Nails 5. CSF 6. Maggots (fly larvae) feeding on the body: In severely decomposed bodies, absence of blood & solid tissues suitable for analysis has led to collection of maggots Example of drugs detected in maggots: Barbiturates, Benzodiazepines, Phenothiazines, Morphine & Malathion All specimens should be collected with clean needle & new syringe The specimens of blood, urine, bile & vitreous should be placed in glass containers, not plastic. WHY? 1 Because these fluids can leach out plastic polymers from the wall of a plastic container 2 If the blood is subsequently analyzed by gas chromatography, the polymers will give peaks that could mask certain compounds & interfere with analysis 3 In some cases, substances such as volatiles can be lost, due to absorption by the plastic 5  Collect blood from femoral vessels. If this is not possible, other sites for collection, in descending order of preference, are: 1. The subclavian vessels 2. The root of the aorta 3. The pulmonary artery 4. The superior vena cava 5. The heart A minimum of 60 mL of blood should be collected into various tubes for processing. One 20 mL red top tube for → Serology testing → contain  no preservative Two 10 mL gray top tubes for → Toxicology testing → contain:  Sodium fluoride → a preservative (Fluoride inhibits invitro metabolism of drugs, especially cocaine)  Potassium oxalate → an anticoagulant Two 10 mL purple top tubes for DNA analysis or genetic studies →  contain: EDTA preservative If volatile intoxication is suspected, a 10 ml glass tube with a Teflon-lined screw top is necessary to prevent diffusion of volatile compounds through a rubber stopper. When collecting specimens, each container should be labeled with: 1. Date & time of autopsy, name of the decedent, identity of the sample, in case of blood, source of blood, e.g., the femorals, an appropriate case identification number. 2. The form is signed & dated by the toxicologist, & subsequently by any individual handling, transferring, or transporting the specimens. 6  (2) Toxicological analyses Before the analysis begins, several factors must be considered, including the amount of specimen available, the predicted nature of the poison, & the possible biotransformation of the poison. In cases involving oral administration of the poison: Gastrointestinal (GI) contents are analyzed first because large amounts of residual unabsorbed poison may be present. Urine may be analyzed next, as the kidney is the major organ of excretion for most poisons. Liver is the first internal organ to be analyzed, because drugs or poisons are carried to the liver from GIT before entering the general systemic circulation. Toxicological analysis is the Qualitative/quantitative analysis of drugs or poisons in biological specimens collected at autopsy by using a variety of analytical procedures: 1. Nonspecific initial tests are designed to determine presence or absence of a class or group of analytes may be performed directly on specimens. Examples of tests used to rapidly screen Urine: Colorimetric tests: e.g. FPN (ferric chloride, perchloric, & nitric acid) detect →phenothiazines Immunoassays: detect → amphetamines, benzodiazepines & opioids 2. Confirmatory tests are more specific tests to identify the actual drug & provide quantitative data To determine a profile of each analyte present in a specimen, chromatographic procedures such as (GC-MS) are used, which facilitates separation & quantification of each compound 7  The most common toxic substances & their analysis Toxic substance Separation method Detection method Examples 1. Volatile Gas Headspace method GC Carbon monoxide agents Liquid GLC Ethanol 2. Corrosive agents Corrosive effects at site of contact of the che mical H2SO4, HCL (mineral acids & bases) & changes in blood che mistry values 3. Nonvolatile organic Urine sample: Colorimetry Phenothiazines agents Immunoassay Amphetamines TLC Benzodiazepines (Drugs, natural Immunoassay Barbiturates products, pesticides, Opioids unclear toxin) Marijuana Blood sample: GC/MS Opioids, Extract with water-immiscible Antidepressants solvent or solid-phase Paracetamol absorbent material HPLC Barbiturates Muscle relaxants Dialysis Colorimetry Some anions trapped GC/MS 4. Anions & nonmetals combined with a stable Ion-s pecific cation, then electrodes can’t detect metal in oxidized state or in combination with other elements. Example: Mercury Atomic Destruction of organic matrix Toxic effects of absorption by chemical or the rmal metallic mercury, 5. Metals spectrometry in mercurous & oxidation leaving the metal as biological fluids mercuric ions, & inorganic residue & tissues dimethyl-mercury are different. Methods selected must determine relative amount of each form (difficult)) 6. Miscellaneous Highly pote nt & difficult to (Venoms, protein Immunoassay mixtures, unclear toxin) isolate substances 8  (3) Interpretation of the analytical findings Toxicologist must interpret his/her findings with regard to physiological or behavioral effects of toxicants on the decedent at the concentrations found. It is often the most challenging aspect for a toxicologist to explain the circumstances surrounding a death Specific questions may be answered, such as: Route of administration? Dose administered? Whether concentration of toxicant present was sufficient to cause death? Or alter decedent’s actions enough to cause his or her death? 9