Branches of forensic toxicology; classification of poisons PDF

Title Branches of forensic toxicology; classification of poisons
Course Pharmacy
Institution University of Nairobi
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CHAPTER 1 INTRODUCTION

Chapter 1: Introduction

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Chapter 1 - Introduction Forensic toxicology Toxicology is a science which deals with the study of poisons. It is a broad field dealing with various aspects of poison starting from lethal dose, form, source, physical and chemical properties. Toxicological studies include different chemical compounds found around along with their effect on the nature. Pharmaceuticals and their derivatives which have been used for medical purposes are also covered under such studies. Any such products which are initially introduced for combating diseases or well being of lives around may show some negative effects too. Such negative effects may lead to stunted growth, disease susceptibility and death. It has got various branches in it including clinical toxicology, chemical toxicology, environmental toxicology, toxicogenomics, occupational toxicology, medical toxicology, regulatory toxicology and forensic toxicology (Smith, 2015).

Figure 1: Branches of Toxicology

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Toxicology came into the present form after a long journey taken up by different toxicologists at different times. One of the most known scientists in toxicology of earlier days was Paracelsus. Theophrastus Phillipus Auroleus Bombastus von Hohenheim commonly referred as Paracelsus is considered as the father of toxicology (Krieger). He has tremendously contributed in the field of toxicology and famously known for his proverb "Alle Dinge sind Gift und nichts ist ohne Gift; allein die Dosis macht, dass ein Ding kein Gift ist." which means, "All things are poisonous and nothing is without poison; only the dose makes a thing not poisonous." (Ottoboni & Frank, 2011)

Paracelsus (also known as: Theophrastus Bombastus von Hohenheim) Swiss physician and alchemist (c. 1493-1541) (Ferguson, 1874) "The dose makes the poison". - Paracelsus (Frank & Ottoboni, 2011).

Paracelsus is also called as the “father of chemistry and the reformer of materia medica,” the “godfather of modern chemotherapy, the “Luther of Medicine,” he was

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the founder of modern toxicology. He was a coeval of Leonardo da Vinci, Martin Luther, and Nicholas Copernicus, he was born on 10 or 14 November 1493, in the village of Einsiedeln near Zurich, Switzerland. His father was a poor man and descendant of Suabia culture. Paracelsus, used to practice the science of alchemy and he believed in three chemicals and their effects a lot i.e. salt (for stability), sulfur (for combustibility) and mercury (for liquidity). As per his understanding diseases is lack of any of the three chemicals mentioned. It was earlier believed by Galenists that a curable disease can be cured using a medicine having opposite effect. It is also referred as principle of contrariety. On the contrary Paracelsus and his supporters believed in the notion of like cures like meaning a poison in harming the body can be cured by using a similar poison by defining a specific dose. It is referred as principle of similitude. Paracelsus suggested that “nature hints at cures”. He thought that the herbal medicines are less effective to fight the diseases around. Eventually he introduced usage of organic salts, metals and minerals to a large extent for curing diseases. Plants started slowly being replaced by chemicals afterwards. His contribution led to usage of chemicals on a large scale for curing diseases. He revolutionized the process of medicinal preparations and their usage. This ultimately led to an era of “New Chemical Medicine” (Borzelleca, 2000) Toxicology has its journey from being a science to cure and assure the well-being of the living beings to its use for criminal investigation. One of the earliest such examples are mentioned in ancient India which consist of stories of homicidal poisoning were popular. Many cultural stories have the incidences of poisoning attached to it. Whether these stories and their glory are myth or truth can’t be said. A concrete form of such writing relating to poisons is mentioned in Charak Samhita and Susruta Samhita which dates back to 600-100 BC. One of the writings in Vedas gives guidelines to identify the poisoners like “He will not answer any question or his answers will be ambiguous. He will speak irrelevant, rubs his toe to the ground and may shiver while speaking. His face will be faded. He will rub his hands on his hair and try to escape the premises. Food which is suspected to be containing poison should be given to animal for confirming the same. The practitioner should be thorough with the knowledge of signs and symptoms of different poisons and their

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respective antidotes in case any enemies of the royals may mix food with poison and try to kill them.” (Trestrail, 2007). Forensic toxicology is that branch of science which applies the knowledge of toxicology and related disciplines like analytical chemistry and pharmacology that assists medico-legal investigations (Forensic Toxicology, 2017). It can be related to death due poisoning and substance of abuse broadly. Unlike clinical toxicology which deals with treating an individual under the influence of poisoning, forensic toxicology is concerned with interpretation of the analytical tests. Since based on the findings the toxicological cases can be reported. Various types of samples are encountered by the forensic toxicologists like urine, blood, stomach wash, tissues etc. An ideal forensic toxicologist should be capable of correlating the signs and symptoms along with the physical evidences collected at a crime scene like pill bottles, unknown powders, traces, and any other chemicals. Knowledge of signs and symptoms along the physical evidence narrows down the search for investigating a poison. The kind of poison as well as the amount of the same should be established. Finally the fatality of the poison and if it is the cause of death has to be affirmed by the forensic toxicologist. Forensic toxicology is based upon various contributions by Mathieu Orfila. He is also considered as the father of toxicology.

Mathieu Orfila (1787 – 1853). (Alchetron)

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He gave one of the very important concepts which is the backbone of the forensic toxicology i.e poisons get absorbed in the body and then is finally accumulated in certain tissues. In 1839 after a lot of effort involving experiments in which a known amount of poison was administered in an animal and was recovered, Orfila demonstrated the recovering arsenic from different organs like kidneys, liver, spleen, muscles and heart of the poisoning case, Soufflard. These methods were adopted by many toxicologists around the globe and if gastrointestinal contents or suspected food or medicine was obtained in the first place then no other toxicological examination were required. In a book “A Treatise on Poisons” by Christison in 1845 acknowledges the value of this discovery and praise Orfila for his contribution. Another book which talks about the duties of an expert was “Poisons in Relation to Medical Jurisprudence and Medicine” which is a classic book in the area of toxicology written by Taylor (1848). The book suggests recovery of arsenic absorbed in the body should be ideally analyzed by the expert. Although in earlier practice only stomach and intestine contents were analyzed and charges were taken for the same. Most of the supporters of Orfilia were against his practice of boiling the entire dead bodies in large iron vessels for examination of toxins. In fact he was condemned for this method which also resulted in many errors in the analysis due to contamination (Myers, 1961). A set of guidelines have been drawn by Orfila for aiding the forensic toxicologists, these guidelines have relevance till date in 21st century. These are briefly discussed below (Cooper & Adam, 2013): 

Whoever takes this work of toxicological examination should have a work experience in toxicology.



The analyst must be provided with every detail of case history which covers all the available information.



Related evidences should be properly packed and labeled in clean containers followed by sealing and submitting the same to the examiner.

Chapter 1: Introduction



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Existing tests should be conducted to examine the samples and writing down the important notes should be of utmost priority.



Reagents used should be pure and blank tests should be performed every time to ensure the purity of the reagents.



Analytical tests should be repeated and compared with control samples for accurate results.

A forensic toxicologist is ideally involved in one of the following types of situations (Cooper & Adam, 2013). : Toxicological investigations Establishing the cause of death due to poisoning. 

Investigating homicidal poisoning or abuse or assault done under the influence of poisoning. Eg. Use of date rape drugs.



Establishing the affect of poison on the culprit and extent of its affect which may influence a person’s behavior to understand the consequences of his/her actions to aid the judicial process. Eg. Substance of abuse.

Human and animal performance testing 

Investigating events under the influence of drugs or alcohol related to crime.



Doping in sports.

Forensic drug testing 

Quality check of drugs to ensure the government policies being followed.



In cases of substance of abuse establishing the drugs taken and history of abuse.

According to American Academy of Forensic sciences (AAFS) within forensic toxicology there are many subfields for eg. Post-mortem toxicology dealing with the

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examination of poison involved in the death and whether the poison was the actual cause of death. It also weighs on the multi-disciplinary nature of the area of forensic toxicology since it requires an individual to work with law enforcement system, pathologists, investigators and other forensic scientists too (Forensic Toxicology Information Guide). Unlike earlier days Forensic Toxicology is no more confined to only criminal investigation. Although it plays an important role in curbing the menace of drug abuse. Since drug problem in India is unique from other countries as it is a neighboring country with golden crescent and golden triangle. Due to wild growth of cannabis naturally, cultivation of poppy and opium production, it is more challenging to deal with drug related issues (Sharma, 1990). Afghanistan, Pakistan and Iran are commonly termed as “golden crescent” along with another such name called “golden triangle” consisting of the countries Laos, Thailand and Burma for high production of opium and drug smuggling (Laciner, 2008).

Figure 2: A world map showing heroin production regions (Golden Crescent., 2017) Courtesy: en.svg)

https://en.wikipedia.org/w/index.php?title=Golden_Crescent&oldid=752169832#/media/File:HeroinWorld-

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Since Gujarat is one of the bordering states to golden crescent it becomes important to have a proper check on the drugs related

issues especially for Gujarat as

compared to any other state. Inter-link of organized crime with terrorist groups is not a hidden fact. Besides nature and extent of this linkage is always explored by various investigation agencies. Development of organized crime in a given state is bigger issue than clubbing of criminal organization and terrorist groups. Among different kinds of organized crimes like smuggling, counterfeiting currency, illegal selling of weapons etc drug smuggling is one of the major ones which contribute in financing the terrorist activities too. This drug smuggling with the purpose of financing the terrorist activities has grown into narco-terrorism, which is a war between many governments and various terrorist groups, insurgents, mafia etc. Narcoterrorism has many dimensions which involves a whole lot of criminals carrying out the black marketing of drugs. Criminals breach laws and national securities of many nations to fulfill their own agenda (Schmid, 2005). As far as India is concerned apart from the geographical positioning of India between the golden crescent and golden triangle, the internal security issues of naxalism have direct links with the drug market being unlawfully handled. These kinds of activities pose serious dangers to the commoners in the country. Such illegal activities lead into formation of clandestine laboratories for producing and circulating drugs. Chemical compounds are mixed and matched to produce designer drugs or street drugs which are difficult to track than the traditional drugs. Designer drug is a derivative of a controlled substance used for recreational purposes which has similar structural or functional properties and gives similar pharmacological effects like the original drug but it does outwit the law since it is not classified earlier with any standards (Wohlfarth & Wolfgang, 2010). Unlike the popular notion that designer drugs are created originally in the laboratory these drugs are borrowed initially from legal pharmaceutical research organizations. With slight alteration in the chemicals, it is then circulated around the market. These drugs need to be studied for better understanding of drugs of abuse around. One of the most common

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classes of drugs which are studied for designer drugs are phenylethylamines (mescaline derivative). Phenylethylamines includes catecholamines and other illicit analogues. Altering the compounds of phenylethylamines gives a range of chemicals which have the capability of stimulating the sympathetic nervous system. Many other compounds used for altering and making designer drugs are as methamphetamine, amphetamine,

3,4-methylenedioxymethamphetamine

(MDMA)

and

3,4-

methylenedioxyamphetamine (MDA). Mis-practicing the designer drugs may lead to fatal results too. Overdosing of such drugs show similar clinical symptoms as in amphetamines like hypertension, mydraisis, tachycardia, agitation, muscle rigidity, hyperthermia and nausea. Cause of death is due to arrhythmias or hyperthermia. Treatment includes supportive care with special care of controlling seizures, body temperature and blood pressure (Buchanan & Christopher, 1988) .Most common designer drugs encountered in the recent years are as follows (Project know-understanding addiction): Ecstasy (“Molly”— A synthetic drug with psychoactive properties which are similar to amphetamines and mescaline) 

“Spice” (artificial marijuana)



Bath salts (consists of one or more synthetic chemicals related to cathinone)



Methylenedioxypyrovalerone (MDPV) (one of the chemicals found in bath salts)



Mephedrone (frequently found in bath salts)



Methylone (generally found in bath salts)



Krokodil (a less-expensive heroin substitute; like heroin, it is a synthetic morphine derivative)

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In Indian context many herbs are potentially used for formulating designer drugs. One of such herbs is Pedicularis densiflora which is popularly called ‘Indian Warrior’ which has aucubin as the active principle. Likewise, Leonotis leonurus also termed as ‘Wild Dagga’ or alternatively called ‘Lion’s Tail’ have similar effects as that of cannabis. On the other hand, addition of synthetic compounds is speculated to be the cause of the pharmacological activity (Auwärter, Dresen, Weinmann, Müller, Pütz, & Ferreirós, 2009). Qualitative and quantitative estimation of illicit drugs which are seized is a laborious task in forensic science and custom department. Dealing with controlled substances is still doable if the substances involved are traditional or already have standard protocol of testing. But when encountered with new derivatives as the seized drugs the problem becomes gross. In 1980s a derivative of fentanyl in California resulted in an epidemic which later coined the term designer drugs. This resulted in stringent laws in United States which influenced the locations of production of designer drugs. Interpretation of designer drugs is problematic due to the unavailability of the standard references of the graphs, retention time or detector response. Although reference standards can be interchanged by certain governments and organizations if there is prior history. But it is a lengthy process. Besides the import and export adds to the cost of the tests. In most of such cases no reference materials are available. (Laks, Pelander, Vuori, Ali-Tolppa, Sippola, & Ojanperä, 2004) Study by Laks Suvi et al suggests method to deal with street drugs which do not have any reference material.

Types of poisons “Poison: Any substance, either taken internally or applied externally, that is injurious to health or dangerous to life.” (Stedman’s Medical Dictionary, 27th ed., 2000, p. 1416) “Poison: Any substance that, when relatively small amounts are injested, inhaled, or absorbed, or applied to, injected into, or developed within the body, has chemical action that causes damage to structure or disturbance of function, producing

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symptoms, illness, or death.” (Dorland’ Illustrated Medical Dictionary, 29th ed., 2000, p. 1422) “A poison in a small dose is a medicine, and a medicine in a large dose is a poison.” (Taylor, 1859, p. 2) Classification of poisons Understanding of poisons can be increased by classifying poisons based on origin, physical form, chemical nature, target site or use (Poison Biochemistry, 2016) : Classification based on origin Origin of poisons can vary from plant, animal, microbial to synthetic. Many plants are poisonous in nature and have potent toxic agents eg. Dhatura, Belladonna and Abarus Precatorius. Active principles of these plants are responsible for the adverse effect on the body. Animal poisons include animal bites and stings of snakes, scorpion, ants and spiders. Microbial organisms also produce toxins which are responsible for hazardous effects. Most common microbial toxin which is observed is botulin produced by Clostridium botulinum. Poisons of synthetic origins have increased in number after the industrial boom. These include pesticides, chemicals of all kinds, drugs, household cleaners etc. Classification based on physical form Based on the physical form a poison can be divided into - solid, liquid, gas or aerosol. Solid poisons do not get easily dissolved in the blood stream, thus, these have more effect when dissolved in the aqueous solution. Granule size of the solids also has effect on toxicity. Smaller the granules higher the toxicity of the poison, since, smaller granules will easily dissolve in an aqueous solution. Likewise solids also do not dissolve with the same rates, eg. Elemental lead is nontoxic when ingested because it is practically insoluble in water but lead sulphate is comparatively soluble.

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Poisonous liquid can be absorbed by ingestion or inhalation or through dermal passage, eg. phenol, pesticides, acids etc. Poisons in the form of gases are introduced in the body through the air passage, in fact vapor forms of liquid are also inhaled sometimes especially in substance of abuse. Among gaseous poisons most common are the gases like carbon monoxide, nitrogen dioxide, sulphur dioxide and also war gases. Vapors may include any organic liquid which is readily volatile like furfural. Small particles of liquid or gaseous nature are called aerosols which are s...


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