8 Forensic Toxicology ALPHONSE POKLIS Introduction To xicology is the study of poisons. More specifically, toxicology is concerned with the chemical and physical properties of toxic substances and their phys- iological effects on living organisms, qualitative and quantitative methods for their analysis in biological and nonbiological materials, and the develop- ment of procedures for the treatment of poisoning. A poison may be regarded as any substance which, when taken in sufficient quantity, will cause ill health or death. The key phrase in this definition is “sufficient quantity”. The inges- tion of large amounts of water over an extended period of time has been known to cause fatal electrolyte imbalance. This seemingly bizarre behavior — ingestion of massive amounts of water — is known as psy- chogenic polydipsia and occurs in certain forms of schizophrenia. Conversely, minute quantities of arsenic, cyanide, and other poisons may be ingested, causing no apparent toxicity. As the 16th century physician Paracelsus observed, “All substances are poisons; there is none which is not a poison. The right dose differentiates a poison from a remedy.” Recently, the science of toxicology has expanded to include a wide range of interests, including the evaluation of the risks involved in the use of pharmaceuticals, pesticides, and food additives, as well as studies of occupa- tional poisoning, exposure to environmental pollution, the effects of radia- tion, and, regretfully, biological and chemical warfare. However, it is the forensic toxicologist who has held the title of toxicologist for the longest period of time. The forensic toxicologist is concerned primarily with the detection and estimation of poisons in tissues and body fluids obtained at autopsy or, occasionally, in blood, urine, or gastric material obtained from a living person. Once the analysis is completed, the forensic toxicologist then interprets the results as to the physiological and/or behavioral effects of the poison upon the person from whom the sample was obtained. In the case of tissues collected at autopsy, the analytical results may reveal that the decedent ©1997 CRC Press LLC died from poisoning. In living persons, the presence of a drug in a blood or urine sample may explain coma, convulsions, or erratic behavior. The complete investigation of the cause or causes of sudden death is an important civic responsibility. Establishing the cause of death rests with the medical examiner, coroner, or pathologist, but success or failure in arriving at the correct conclusion frequently depends upon the combined efforts of the pathologist and the forensic toxicologist. Poisoning as a cause of death cannot be proven beyond contention without toxicologic analyses that dem- onstrate the presence of the poison in the tissues or body fluids of the deceased. Most drugs and poisons do not produce characteristic or observ- able lesions in body tissues, and their presence can be demonstrated only by chemical methods of isolation and identification. If toxicological analyses are avoided, death may be ascribed to poisoning without definite proof, or a death due to poisoning may be erroneously attributed to some other cause. In instances where death is not due to poisoning, the forensic toxicologist can often provide valuable evidence concerning the circumstances surround- ing a death. The erratic driving behavior of the victims of automotive acci- dents is often explained by the presence of alcohol in blood or tissues. Psychoactive drugs, those which affect behavior, often play a significant role in circumstances associated with sudden or violent death. The detection of alcohol, narcotics, hallucinogens, or other drugs may substantiate the testi- mony of witnesses as to the aggressive, incoherent, or irrational behavior of the decedent at the time of a fatal incident. Conversely, negative toxicology findings may dispel stories of the decedent’s drug use. Negative findings are also significant in persons who should be regularly taking medications to control pathological conditions. In the case of epileptics, negative or low drug concentrations may indicate the decedent was not taking his medication in the prescribed manner and as a result experienced a fatal seizure. History of Forensic Toxicology Until the 19th century, physicians, lawyers, and law enforcement officials harbored extremely faulty notions about the signs and symptoms of poison- ing. It was traditionally believed that if a body was black, blue, or spotted in places or “smelled bad” the decedent had died from poison. Other mistaken ideas were that the heart of a poisoned person could not be destroyed by fire, or that the body of a person dying from arsenic poisoning would not decay. Unless a poisoner was literally caught in the act, there was no way to establish that the victim died from poison. In the early 18th century, a Dutch physician, Hermann Boerhoave, theorized that various poisons in a hot, vaporous con- dition yielded typical odors. He placed substances suspected of containing ©1997 CRC Press LLC poisons on hot coals and tested their smells. While Boerhave was not suc- cessful in applying his method, he was the first to suggest a chemical method for proving the presence of poison. During the middle ages, professional poisoners sold their services to both royalty and the common populace. The most common poisons were of plant origin (such as hemlock, aconite, belladonna) and toxic metals (arsenic and mercury salts). During the French and Italian Renaissance, political assassi- nation by poisoning was raised to a fine art by Pope Alexander VI and Cesare Borgia. The murderous use of white arsenic (arsenic trioxide) became so wide- spread among the general population that the poison acquired the name “inheritance powder”. Given this popularity, it is small wonder the first mile- stones in the chemical isolation and identification of a poison in body tissues and fluids would center around arsenic. In 1775, Karl Wilhelm Scheele, the famous Swedish chemist, discovered that white arsenic was converted to arsenous acid by chlorine water. The addition of metallic zinc reduced the arsenous acid to poisonous arsine gas. If gently heated, the evolving gas would deposit metallic arsenic on the surface of a cold vessel. In 1821, Sevillas used the decomposition of arsine to detect small quantities of arsenic in stomach contents and urine in poisoning cases. In 1836, James M. Marsh, a chemist at the Royal British Arsenal in Woolwich, used the generation of arsine gas to develop the first reliable method to determine an absorbed poison in body tissues and fluids, such as liver, kidney, and blood. The 1800s witnessed the development of forensic toxicology as a scientific discipline. In 1814, Mathieiv J. B. Orfila (1787–1853), the “father of toxicol- ogy”, published Traité des Poisons — the first systemic approach to the study of the chemical and physiological nature of poisons. Orfila’s role as an expert witness in many famous murder trials, and particularly his application of the Marsh Test for arsenic in the trial of the poisoner Marie Lafarge, aroused both popular and scholarly interest in the new science. As Dean of the Medical Faculty at the University of Paris, Orfila trained many students in forensic toxicology. The first successful isolation of an alkaloid poison was performed in 1850 by Jean Servials Stas, a Belgian chemist, using a solution of acetic acid in ethyl alcohol to extract nicotine from the tissues of the murdered Gustave Fougnie. Modified by the German chemist, Friedrich Otto, the Stas-Otto method was quickly applied to isolation of numerous alkaloid poisons, including colchicine, conin, morphine, narcotine, and strychnine; the method is still used today. In the second half of 19th century, European toxicologists were in the forefront of the development and application of forensic sciences. Procedures were developed to isolate and detect alkaloids, heavy metals, and volatile poisons. ©1997 CRC Press LLC In America, Rudolph A. Witthaus, Professor of Chemistry at Cornell University Medical School, made many contributions to toxicology and called attention to the new science by performing analyses for New York City in several famous poisoning cases: the murders of Helen Potts by Carlyle Harris and of Annie Sutherland by Dr. Robert W. Buchanan, both of whom used morphine. In 1911, Tracy C. Becker and Professor Witthaus edited a four-vol- ume work on medical jurisprudence, Forensic Medicine and Toxicology, the first standard forensic textbook published in the U.S. In 1918, the City of New York established a medical examiner’s system, and the appointment of Dr. Alexander O. Gettler as toxicologist marked the beginning of modern forensic toxicology in America. Although Dr. Gettler made many contribu- tions to the science, perhaps his greatest was the training and direction he gave to future leaders in forensic toxicology. Many of his associates went on to direct laboratories within coroner and medical examiner systems in major urban centers throughout the country. In 1949, the American Academy of Forensic Sciences was established to support and further the practice of all phases of legal medicine in the U.S. The members of the toxicology section represent the vast majority of forensic toxicologists working in coroners’ or medical examiners’ offices. Several other international, national, and local forensic science organizations, such as the Society of Forensic Toxicologists and the California Association of Toxicol- ogists, offer forums for the exchange of scientific data pertaining to analytical techniques and case reports involving new or infrequently used drugs and poisons. The International Association of Forensic Toxicologists, founded in 1963, with over 750 members in 45 countries, permits worldwide cooperation in resolving technical problems confronting the toxicologist. In 1975, the American Board of Forensic Toxicology was organized to examine and certify forensic toxicologists. One of its stated objectives is “to make available to the judicial system, and other public, a practical and equi- table system for readily identifying those persons professing to be specialists in forensic toxicology who possess the requisite qualifications and compe- tence”. In general, those certified by the Board must have an earned Doctor of Philosophy or Doctor of Science degree, have at least 3 years full-time professional experience, and pass a written examination. At present, only about 200 toxicologists are certified by the Board. Deaths Investigated by Toxicologists Accidental Poisoning Most accidental poisonings occur in the home. Children, due to their innate curiosity and adventurous nature, may gain access to and ingest prescription ©1997 CRC Press LLC drugs, detergents, pesticides, and household cleaners. Fortunately, public awareness of the safe storage of household chemicals, safety top containers, the availability of poison control information centers, and better emergency- room procedures for treating child poisonings have all contributed to a marked decrease in this type of death. Accidental poisoning in adults is usually the results of mislabeling, storage of a toxic substance in a container other than the original one. As often as not, the improper container is an old whiskey bottle! Arsenic, weed killer, strychnine, cyanide, cleaning solu- tions, and numerous other deadly poisons have been eagerly and mistakenly drunk from cider jugs and old whiskey bottles. An open container of cyanide next to a tin of sugar on a basement work bench has been known to sweeten a final cup of coffee. Accidental poisonings may occur in industry due to carelessness or mis- haps which expose workers to toxic substances. While the potential for acci- dental poisonings in industry is great, safety standards and regulations and the availability of emergency medical services today prevent industry from being a source of many fatal intoxications. Deaths from Drug Abuse Drug abuse, the nonmedical use of drugs or other chemicals for the purpose of changing mood or inducing euphoria, is the source of many poisonings. Drug abuse may involve the use of illicit drugs such as heroin or phencycli- dine; the use of restricted or controlled drugs such as cocaine, barbiturates, and amphetamine; or use of chemicals in a manner contrary to their intended purpose — such as inhaling solvents and aerosol products. Since the devel- opment and glorification of the “drug culture” in the mid-1960s, deaths due to illicit drug use are the most common fatal poisonings investigated by toxicologists, particularly in large urban areas. Table 8.1 presents the drugs most commonly encountered in death investigations; note the high incidence of cocaine, alcohol, and heroin/morphine. In a broader sense, drug abuse may also include the excessive use of legal substances, such as alcohol and prescription drugs. The use of alcohol is the biggest drug problem in the U.S. Alcohol plays a significant role in violent deaths. Of the 40,000 automobile accident deaths that occur annu- ally in the U.S., 50% involve drinking drivers, and 60% of pedestrians killed have significant blood alcohol levels. Of urban adults who were admitted to a hospital with a fractured bone, 50% fractured the bone during or after drinking. Significant blood alcohol levels are found at autopsy in 35% of all persons committing suicide and in 50% of all murder victims. Also, many people die each year due to many pathologic conditions directly attributed to alcohol or complications of other pathologic conditions aggravated by alcohol consumption. Alcohol is a self-limiting poison: ©1997 CRC Press LLC people usually lose consciousness before a lethal dose is ingested. Therefore, overdose deaths due to the ingestion of excessive quantities of alcohol are uncommon. However, numerous accidental deaths occur from the concur- rent ingestion of potent prescriptions drugs and alcohol. Suicidal Poisoning Suicide is a common manner of death in cases of poisoning. In general, about twice as many men successfully commit suicide as women. However, twice as many women attempt to commit suicide with poison as men. The most common suicidal agent is carbon monoxide, a gas generated by the incom- plete combustion of carbonaceous compounds. Automobile exhaust contains a substantial concentration of carbon monoxide. Allowing a car motor to run in a closed garage is the usual method used by those who commit suicide with carbon monoxide. While cyanide, arsenic, and other well known poisons may be occasionally used as suicidal agents, most deaths result from pre- scription drugs. Persons suffering from depression and other emotional dis- turbances usually have available a supply of potent and, if taken in excess, deadly drugs to combat the symptoms of their psychological disorders. Today, most suicidal poisonings involve multiple drug ingestion; usually three to seven different drugs are ingested at one time. By analyzing the gastric and bowel contents, blood, urine, and the major organs of the body, the toxicol- ogist can determine the minimum quantity of the poison ingested. In sui- cides, the results of such analysis demonstrate that a massive quantity was taken; this establishes beyond doubt that the decedent could not have acci- dentally taken such a dose. Table 8.1 Drugs Most Frequently Encountered in Medical Examiners Cases, 1991 a Rank Drug Name Number of Mentions Percent b of Total Episodes 1Cocaine 3,020 45.75 2Alcohol — in combination 2,436 36.90 3Heroin/Morphine 2,333 35.3 4Codeine 783 11.86 5Diazepam 587 8.89 6Amitriptyline 437 6.62 7Methadone 430 6.51 8Nortriptyline 379 5.74 9 d-Proxpoxyphene 325 4.92 10 Diphenhydramine 241 3.65 a Drug Abuse Warning Network, National Institute on Drug Abuse data from 27 metropolitan areas. b Percent of total episodes may exceed 100%, as a single case may involve more than one drug. ©1997 CRC Press LLC Homicidal Poisoning Accidental and suicidal poisonings are common today; murder by poison is rare. Determining that a person died as the result of homicidal poisoning is often the most difficult type of investigation for law enforcement officers and medical experts. The general evidence of poisoning is obtained from a knowl- edge of the symptoms displayed by the decedent before death, the postmor- tem examination of the body by the pathologist, and the isolation and identification of the poison by the toxicologist. For successful prosecution of a suspect, law enforcement officers must establish that the perpetrator had access to a supply of the poison, that the suspect was aware of the lethal effects of the poison, and that the suspect had opportunity to administer the poison to the decedent. When the victim is attended to, before death, by a physician, the doctor seldom, if ever, considers poisoning as a cause of the patient’s ills. Only if the patient’s occupation brings him into contact with toxic substances (works in a refinery, chemical, or smelting plant; works on a farm and uses pesticides and herbicides) will the physician suspect a chemical intoxication. Murder by poison most commonly occurs within the home, and the physician will seldom suspect a bereaved husband, wife, son, or daughter of poisoning another family member. Also, there is rarely any symptom of poisoning which cannot equally well be caused by disease. Vomiting, diarrhea, rapid collapse, and weak pulse, all symptoms of arsenic poisoning, may also be due to a ruptured gastric ulcer or an inflammation of the pancreas or appendix. Likewise, both strychnine and tetanus cause convulsions. Contracted pupils and narcosis may be from narcotic drugs or brain lesions. However, there are circumstances which render a diagnosis of poisoning moderately certain. The onset and progression of symptoms to rapid death immediately after eating or drinking indicate acute poisoning, since bacterial food poisoning has a delayed onset of symptoms. The pathologist can recognize the effects of certain poisons at autopsy. Strong acids and alkalis may cause extensive burns around the mouth or the surface of the body, with severe destruction of the internal tissues. Metallic poisons may cause intensive damage to the gastrointestinal tract, liver, and kidneys. Phosphorus, chlorinated hydrocarbons, and poisonous mushrooms cause gross fatty degeneration of the liver. However, most poisons do not produce observable changes in body tissue; hence, in many instances of poisoning, the value of the pathologist’s examination of the body is estab- lishing that death was not due to natural causes or traumatic injury and that there is no evidence for cause of death except from possible poisoning. In most cases, toxicological analysis produces evidence for murder by poison. ©1997 CRC Press LLC Toxicological Investigation of a Poison Death The toxicological investigation of a poison death may be divided into three steps: 1. Obtaining the case history and suitable specimens 2. The toxicological analyses 3. The interpretation of the results of the analyses Case History and Specimens To day, there are readily available to the public thousands of compounds that are lethal if ingested, injected, or inhaled. The toxicologist has only a limited amount of material on which to perform his analyses; therefore, it is imper- ative that, before beginning the analyses, he or she is given as much infor- mation as possible concerning the facts of the case. The toxicologist must be aware of the age, sex, weight, medical history, and occupation of the decedent, as well as any treatments administered before death, the gross autopsy find- ings, drugs available to the decedent, and the time interval between the onset of symptoms and death. In a typical year, the toxicology laboratory of a medical examiner’s office will perform analyses on tissues for such diverse poisons as prescription drugs (analgesics, antidepressants, hypnotics, tran- quilizers), drugs of abuse (hallucinogens, narcotics, stimulants), commercial products (antifreeze, aerosol products, insecticides, rodenticides, rubbing compounds, weed killers), and gases (carbon monoxide, cyanide). Obviously, the possible identity of the poison prior to analysis would greatly help. The collection of specimens for toxicological analysis is usually per- formed by the pathologist at autopsy. Specimens from numerous body fluids and organs are necessary as drugs and poisons display varying affinities for the body tissues (see Table 8.2). Drugs and poisons are not distributed evenly Table 8.2 Exhibits Collected at Autopsy for Toxicological Analysis Specimen Quantity Toxicant Sought Adipose tissue 200 g Insecticides, thiopental Bile All available Codeine, morphine Blood 15 ml Alcohols, carbon monoxide Brain 500 g Volatile poisons Kidney One whole organ Heavy metals Liver 500 g Most toxicants Lung organ One whole Methadone, gases, inhalants Stomach and intestinal contents All available All toxicants taken orally Urine All available Most toxicants Vitreous humor All available Digoxin, electrolytes, glucose ©1997 CRC Press LLC throughout the body, and the toxicologist usually first analyzes those organs expected to have the highest drug concentrations, Figure 8.1. A large quantity of each specimen is needed for thorough toxicological analysis because a procedure which extracts and identifies one compound or class of com- pounds may be ineffective in extracting or identifying others. In collecting the specimens, the pathologist labels each container with the date and time of autopsy, the name of the decedent, the identity of the sample, and the signature of the pathologist. The toxicologist, when receiving the specimens, gives the pathologist a written receipt and stores the specimens in a locked refrigerator until analysis. This procedure provides an adequate chain of custody for the specimens which enables the toxicologist to intro- duce his results into any legal procedures arising from the case. Specimens should be collected before embalming, as this process may destroy or dilute the poisons present and render their detection impossible. For example, cyanide is destroyed by the embalming process. Conversely, methyl or ethyl alcohol may be a constituent of an embalming fluid, thus giving a false indication of the decedent’s drinking prior to death. Toxicological Analysis Before beginning the analysis, the toxicologist must consider several factors: the amount of specimen available, the nature of the poison sought, and the possible biotransformation of the poison. Because he is working with a Figure 8.1 Distribution of cocaine in cases of fatal intravenous injection. (Data from Poklis, et al., J. Anal. Toxicol., 9, 227, 1985. With permission.) ©1997 CRC Press LLC limited amount of specimen, the toxicologist must devise an analytical approach which will allow the detection of the widest number of compounds. Figure 8.2 outlines a schema for the isolation of poisons when the offending compound is not known. In cases involving oral administration of the poison, the gastrointestinal contents are analyzed first, since large amounts of residual unabsorbed poison may be present. The urine may be analyzed next, as the kidneys are the major organ of excretion for most poisons and high concen- trations of toxicants are often present in urine. Following absorption from the gastrointestinal tract, drugs or poisons are first carried to the liver before entering the general systemic circulation; therefore, the first analysis of an internal organ is conducted on the liver. If a specific poison is suspected or known to be involved in a death, the toxicologist chooses to first analyze those tissues and fluids in which the poison concentrates. Figure 8.2 Schema for isolation of poisons. ©1997 CRC Press LLC [...]... experienced examiners to show them how to see, how to interpret, how to evaluate, and how to reason On-the-spot, full-time supervision is needed to critique and to correct Trainees need face -to- face instruction on how to avoid making mistakes in judgments that so seriously affect others Trainees need a wide range of training cases These exist only in the files of established laboratories, not in books,... history, taking into account all the above factors of toxicity, distribution, and biotransformation and comparing the analytic results with similar cases reported in the professional literature or similar cases from his own experiences, does the toxicologist write his final interpretation of a case The Toxicologist as Expert Witness The forensic toxicologist is often called on to testify in court as to. .. are often the best indicators of toxicity; consequently, blood is a most valuable specimen to the toxicologist To interpret blood or tissue levels properly, the toxicologist must consider all factors which influence obtaining a given toxicant concentration in a specimen Interpretation of blood or tissue values may be divided into three categories: (1) normal or therapeutic, (2) toxic, and (3) lethal A... Publishing, New York, 1988 5 Introduction to Forensic Toxicology, R H Cravey and R C Baselt, Biomedical Publications, Davis, CA, 1981 SERIES 1 Advances in Analytical Toxicology, R H Baselt, Ed., Yearbook Medical Publishers, Boca Raton, FL 2 Methodology for Analytical Toxicology, Vol 1, 2, and 3, I Sunshine, Ed., CRC Press, Boca Raton, FL ©1997 CRC Press LLC Questioned Documents 9 WILLIAM H STORER Death, drugs,... analysis of the specimens is completed, the toxicologist must interpret the findings as to the physiological effects of the toxicants on the decedent at the concentrations found Specific questions as to route of administration, whether or not the concentration of the toxicant present was sufficient to cause death or to alter the decedent’s actions so as to contribute to his death, must be answered Assessing... questions into pointless harassment That is why document examiners must also be good photographers What you say and demonstrate in criminal court can often be the push that sends a defendant to prison, sometimes to death row What you say and ©1997 CRC Press LLC demonstrate in civil court can make or destroy a litigant’s financial future And what you report to investigators and to prosecutors can be... they are asked to do Later in this chapter you will see some questions that civil attorneys, prosecutors, defense attorneys, investigators, and assorted clients put to document examiners, but first… Who Should Not Consider a Career in This Field? Here are some considerations that might eliminate your choosing this forensic career First, you must have good vision Your eyes will be your basic tool for finding... death In the investigation of a poisoning, it is first necessary for the toxicologist to isolate and identify the poison Therefore, forensic toxicologists group poisons according to the method used to isolate the substances from body tissues or fluids Group I: Gases Most gases of toxicological significance are not detectable in autopsy specimens However, some may be isolated from blood or lung tissue... one specific science area is not required But you are strongly urged to consider at least a minor in one of the laboratory sciences, such as chemistry Some document examiners have a degree in criminalistics As document examiner, you will be doing laboratory work with laboratory tools, so your schooling should be laboratory oriented Laboratory science credits that include microtechniques will be your armor... /stop, exposure index, focal length, fine grain, guide numbers, filter factors, infrared photography, ultraviolet photography, macrophotography, microphotography Cameras are necessary investigating and reporting tools You will use cameras to discover and decipher erasures, eradications, and obliterations on documents You will use cameras to decipher and record invisible entries on burned documents And you . toxicologist. In 1975, the American Board of Forensic Toxicology was organized to examine and certify forensic toxicologists. One of its stated objectives is to make available to the judicial system, and other. 8 Forensic Toxicology ALPHONSE POKLIS Introduction To xicology is the study of poisons. More specifically, toxicology is concerned with the chemical and physical properties of toxic. b of Total Episodes 1Cocaine 3,020 45 .75 2Alcohol — in combination 2 ,43 6 36.90 3Heroin/Morphine 2,333 35.3 4Codeine 783 11.86 5Diazepam 587 8.89 6Amitriptyline 43 7 6.62 7Methadone 43 0 6.51 8Nortriptyline