Description

Poisoning is injury or death due to swallowing, inhaling, touching, or injecting various drugs, chemicals, venoms, or gases. Mass poisoning is characterized by the occurrence of similar symptoms in a group of previously healthy people in a narrow time frame. Similar to the definition of “mass” in mass murder or mass grave, mass poisoning refers to the poisoning of three or more victims in a single incident at a single location. However, this definition is problematic for multiple reasons: (1) the implication of “mass” is usually of a multitude of victims, many more than three; (2) requiring so few victims to meet the definition does not adequately distinguish mass poisoning from poisoning in general; and (3) a “single location” is too vague with an implication that is too restricted spatially. For the purposes of this chapter, mass poisoning will consider events of chemical poisoning involving at least 50 victims that result from the same source or circumstances, whether restricted to a single locale or more spatially dispersed, and whether restricted to a single point in time or serialized over a longer period (but usually within a few weeks or months).

This article will not comprehensively address iatrogenic poisoning (ie, toxicity from drugs that have not been adulterated when used appropriately from a medical perspective), which involves issues of drug evaluation, drug regulation, trade-offs between benefit and risk, and issues of manufacturing quality control. This article will also not cover radiation poisoning. Occupational, environmental, and psychogenic mass poisoning are addressed in separate Medlink Neurology articles.

The responsible toxic agent of a mass poisoning event may not be identified during the early stage of the event, especially if mass poisoning results from oral exposure. The toxicity of sources can be inherent to the agent itself or result from contamination.

Although most mass poisonings are unintended, many have resulted from intentional action (eg, adulteration of alcoholic beverages with methanol, adulteration of medical drugs with agents showing higher toxicity than the drug itself, mass murder, genocide).

Heavy metals have been implicated in mass poisonings in occupational poisoning (arsenic, lead, manganese, mercury), environmental poisoning (eg, arsenic, lead, mercury), mass murder (arsenic), and historically in iatrogenic poisoning (eg, mercury and arsenicals for syphilis). Other implicated substances in occupational mass poisoning events (eg, n-hexane) have affected much smaller numbers of people.

The poisons used in mass poisonings can be categorized by the circumstances of poisoning into (1) adulteration, (2) contamination, (3) recreational (usually with intended intoxicants), (4) occupational exposure (ie, poisoning of workers), (5) iatrogenic (ie, toxic substances are intentionally administered because the therapeutic benefit is believed to outweigh the risks from adverse effects of the substances), (6) environmental exposure (ie, with poisons released intentionally or otherwise into a shared environment), (7) mass suicide, (8) mass murder (with multiple subcategories: non-terrorism mass murder, terrorism mass murder, war crimes, genocide), (9) psychogenic, and (10) unknown or unclear (Table 1). Some substances can cause several different kinds of mass poisonings. For example, arsenic has caused mass poisonings by contamination, adulteration, occupational exposure, environmental exposure, and mass murder. Some events are not classifiable because the responsibility and intent are unclear.

Table 1. Categorization of Mass Poisoning Events*

Adulteration

Adulteration means to corrupt foods, drugs, or dietary supplements by adding a foreign or inferior substance, typically to prepare foods or drugs for sale by replacing more valuable ingredients with less valuable ones. Adulterants are substances added to foods, drugs, and dietary supplements (either intentionally or by accident) but not listed as an ingredient. An adulterant may cause a product to be harmful or not work as it should.

In some cases, the adulterating substances can be toxic (eg, adding cheaper methanol to ethanol as was done during Prohibition in the United States and continues to be done in various countries, especially by poor individuals). The intent of adulteration is usually financial without an attempt to harm, but it may be financial with the recognition that the added substance is harmful (eg, the sale of ethanol adulterated with methanol to American Indians by unscrupulous white profiteers in the early 20th century), or it may be malicious (eg, acts of murder or terrorism).

The Plague of Adulteration: A Popular Complaint to a Popular Air

Under the 1938 Federal Food, Drug, And Cosmetic Act (21 U.S. Code § 342) as amended, food, drugs, or dietary substances are considered adulterated if any of the following apply (summarized from the original lengthy legal verbiage):

Clinical applications

Adulteration

Arsenic.

Table 2. Mass Poisoning Due to Adulteration with Arsenicals

Bradford sweets poisoning (1858). In the 1858 Bradford sweets poisoning, more than 200 people in Bradford, England, were poisoned with arsenic that had been accidentally incorporated into candies during preparation. The event contributed to the passage of the Pharmacy Act 1868 in the United Kingdom and legislation regulating the adulteration of foodstuffs.

William Hardaker, known as “Humbug Billy,” sold sweets from a stall in the Greenmarket in central Bradford. Hardaker purchased his supplies from Joseph Neal, who made the sweets (or “lozenges”). The lozenges were peppermint “humbugs” (ie, hard candies, especially ones flavored with peppermint), made from a base of sugar and gum with peppermint oil added for flavor. However, because sugar was expensive, Neal routinely substituted inexpensive powdered gypsum for some of the sugar (the gypsum was known as “daff” and, by weight, cost less than 8% of the cost of sugar). On October 30, 1858, Neal sent James Archer, a lodger at his house, to collect daff from druggist Charles Hodgson. Hodgson was at the pharmacy but was ill, so his young assistant, William Goddard, attended to Archer. Goddard asked Hodgson where the daff was and was told that it was in a cask in a corner of the attic. However, rather than daff, Goddard accidentally sold Archer 12 pounds (5.4 kg) of arsenic trioxide. The mistake remained undetected during the preparation of the sweets by James Appleton, an “experienced sweetmaker” employed by Neal. Appleton became ill during the process and remained ill for several days afterward, suffering with vomiting and pain in his hands and arms, but did not realize a poison caused it. Neal sold 40 pounds (18 kg) of lozenges to Hardaker. Although Hardaker tasted the sweets and promptly became ill, he nevertheless sold 5 pounds (2.3 kg) to patrons that night. Of those who purchased and ate the sweets, 21 people died, and 200 or so more became severely ill within a day.

The first deaths of two children were initially attributed to cholera, but the rapid increase in casualties soon showed that the lozenges from Hardaker's stall were responsible. Goddard was arrested and was questioned by magistrates in the Bradford courthouse on November 1. Goddard, Hodgson, and Neal were all subsequently committed for trial on a charge of manslaughter. Dr. John Henry Bell (1832-1906) identified arsenic as the cause of the mass poisoning, which was confirmed by forensic analytical chemist Felix Rimmington (1818-1897) (18; 55). Rimmington estimated that each humbug contained between 14 and 15 grains (910-970 mg) of arsenic, several times the lethal dose of 4.5 grains (290 mg). The prosecution against Goddard and Neal was later withdrawn, and Hodgson was acquitted at the York Assize on December 21, 1858 (An assize was a periodical court that sat at intervals in each county of England and Wales to administer civil and criminal law).

The tragedy and public reaction served as a major stimulus to the passage of (1) the Pharmacy Act of 1868, which recognized the chemist and druggist as the custodian and seller of named poisons, and (2) the Sale of Food and Drugs Act of 1875, which regulated the adulteration of foods and drugs.

Triorthocresyl phosphate (TOCP). Numerous mass poisoning events have been attributed to triorthocresyl phosphate (TOCP; tri-O-cresyl phosphate) and organophosphate compound (Table 3) (172; 168; 73; 196; 114). Cresol (C7H8O) refers to any of the three methylphenols: ortho- (o-) cresol, meta- (m-) cresol, and para- (p-) cresol. Cresols are obtained from coal tar or petroleum, usually as a mixture (tricresol or cresylic acid) of the three stereoisomers. All three isomers are highly toxic. Triorthocresyl phosphate is an organophosphate with three orthocresol moieties bound to a phosphate. Like organophosphate nerve agents, triorthocresyl phosphate causes organophosphate-induced delayed neurotoxicity (OPIDN) that often manifests as spastic paraparesis.

Jamaica ginger extract (Jake). Jamaica ginger extract, known in the United States by the slang name “Jake,” was a late-19th-century patent medicine, sold in drug stores and at roadside stands since the 1860s, that provided a source of ethanol during the Prohibition era because it contained approximately 70% to 80% ethanol by weight. During the early 1930s, at the end of the Prohibition Era (1920-1933), an estimated 30,000 men in the American South and Midwest developed arm and leg weakness and pain after drinking “Ginger Jake,” which contained a Jamaican ginger extract adulterated with TOCP (20; 21; 22; 33; 37; 53; 98; 47; 57; 65; 59; 39; 87; 86; 180; 186; 207; 28). The damage resulted in the limping “Jake Leg,” “Jake Leg Wobble,” “Jake Limber Leg,” or “Jake Walk,” which were terms frequently used in the blues music of the period (106; 195; 108): “Jake leg blues” (1928, 1930, 1934), “ Alcohol and Jake Blues” (1930), “Jake Leg Rag” (1930), “Jake Leg Wobble” (1930), “ Jake Liquor Blues” (1930), “Got the Jake leg too” (1930), and “Jake Walk Papa” (1933).

In 1930, Jamaican ginger paralysis was linked to adulteration with TOCP by Maurice Isadore Smith MD (1887-1951), Principal Pharmacologist and Chief of the Section on Pharmacology in the Laboratory of Pathology and Pharmacology, Experimental Biology, and Medicine Institute, and Elias Elvove PhD (1883-1962), Senior Chemist, Laboratory of Chemistry, National Institutes of Health, United States Public Health Service (160; 159; 161; 155; 158; 162; 154; 155; 156; 157; 155; 157; 23; 24; 129). Smith and Elvove were both Russian emigres who were educated in the United States and later became influential scientists at the National Institutes of Health.

Europe experienced outbreaks of TOCP poisoning with resultant neuropathy and some deaths from intentionally contaminated abortifacients in the 1930s, and South Africa experienced a similar outbreak in the 1950s (176; 140; 172).

Over a period of 3 weeks, in the fall of 1959, Morocco experienced an epidemic of paralysis from TOCP poisoning. Victims were poor Arab families poisoned by using olive oil adulterated with TOCP “by unscrupulous profiteers to increase its bulk” (151; 58; 134; 131; 178). TOCP was an ingredient of a detergent cleansing fluid used to flush jet engines and was acquired at a cheaper price than olive oil. The cheaper price of adulterated olive oil led to the selective poisoning of people with meager financial resources.

The Moroccan police seized all the olive oil available at that time in Morocco, which terminated the epidemic. Nevertheless, by the end of September 1959, 10,466 individuals had been afflicted.

Table 3. Mass Poisoning Events with Triorthocresyl Phosphate (TOCP) *

Contamination

Arsenic.

English beer poisoning (1900). In 1900, a mass poisoning epidemic affected more than 6,000 people in England, who were poisoned by arsenic-tainted beer (51; 83; 138; 139; 84; 137; 81; 82; 132; 44; 54). Of those afflicted, 70 died. The food safety crisis was caused by arsenic entering the supply chain through impure sugar made with contaminated sulfuric acid. The illness was prevalent across the Midlands and North West England, with Manchester being the most heavily affected. Originally misdiagnosed as alcoholic neuropathy, the main epidemic was only recognized after 4 months.

In November 1900, Ernest Septimus Reynolds (1861-1926), Assistant Physician to the Manchester Royal Infirmary and Visiting Physician to the Manchester Workhouse Infirmary, announced “An epidemic of peripheral neuritis amongst beer drinkers in Manchester and district” and attributed this to arsenic poisoning (138; 139):

Reports confirming and expanding Reynold's observations appeared within weeks (51; 83; 84; 137). A Royal Commission chaired by Lord Kelvin (Sir William Thomson; 1824-1907) published its final report in 1903 (81; 82).

“L'affaire de la poudre Baumol” (“the Baumol powder affair,” 1952). This health scandal took place in France, mainly in the South West and Brittany, in 1952 (56; 89; 90). Because of a manufacturing error, a talc preparation for babies was contaminated with an arsenical compound, causing about 500 casualties, including 82 deaths. Baumol powder, as originally developed by the Francam laboratories in 1914, consisted of a combination of talc powder (talcum, a clay mineral composed of hydrated magnesium silicate) and zinc oxide with a lavender perfume. The Daney laboratories purchased the business in 1951. When they manufactured the baby powder, they accidentally replaced zinc oxide with arsenious anhydride (ie, the anhydride form of arsenous acid, or arsenic trioxide), which is used as a herbicide, pesticide, and rodenticide. The laboratory was found to be negligent with quality control, both of ingredients and finished products. The first health alerts were raised in the spring of 1952, and the product sale was banned in late October of the same year.

Morinaga milk poisoning (1955). In the early summer of 1955, more than 2,113 bottle-fed Japanese infants were poisoned by arsenic, with more than 100 deaths, due to arsenic-contaminated milk powder produced by the Morinaga Company (50). The source of arsenic contamination was an industrial-grade disodium phosphate product added to cow's milk as a stabilizer to preserve constant acidity, but this was of low purity and contained significant amounts of sodium arsenate (Na₃AsO₄) (50).

Table 4. Mass Poisoning by Contamination with Arsenicals

Organomercury.

Table 5. Mass Poisoning by Contamination with Organomercury Compounds

Pesticides.

Table 6. Pesticide Mass Poisoning Events

Hexachorobenzene. Hexachlorobenzene or perchlorobenzene, an aryl chloride compound, was used as a fungicide and pesticide until 1965 and was also used in the production of rubber, aluminum, and dyes and in wood preservation. As a fungicide, it was formerly used as a seed treatment, especially on wheat to control the fungal disease bunt.

Table 7. Mass Poisoning Due to Contamination with Hexachorobenzene

Hexachlorophene (disinfectant). In the “Affaire du talc Morhange” (Morhange talc affair) in 1972, 204 children in the northeastern French community of Morhange became ill, and 39 died in an epidemic of percutaneous poisoning. Affected children developed ulcerative skin lesions, diarrhea, encephalopathy with convulsions, and coma. The toxic agent was a contaminant of talc “baby powder”; because of a manufacturing error, the baby powder contained 6.3% hexachlorophene, an organochlorine compound. The cause of the epidemic was established by chemical analysis of the talc, high hexachlorophene levels and characteristic histological findings in affected children, and toxicity tests in animals (95; 96). In 1972, the U.S. Food and Drug Administration halted the production and distribution of products containing more than 1% hexachlorophene.

Table 8. Mass Poisoning Due to Contamination with Hexachlorophene

Domoic acid.

Table 9. Mass Poisoning Due to Contamination of Mussels with Domoic Acid

Bongkrekic acid.

Mozambique funeral beer poisoning (bongkrekic acid). Bongkrekic acid (also known as bongkrek acid) is a respiratory toxin produced in fermented coconut or corn mash that is contaminated by the bacterium Burkholderia gladioli pathovar cocovenenans. Bongkrekic acid is a highly toxic, heat-stable, colorless, odorless, unsaturated tricarboxylic acid that inhibits ADP/ATP translocase (the mitochondrial ADP/ATP carrier), preventing ATP from leaving the mitochondria to provide metabolic energy to the rest of the cell. Bongkrek acid, when consumed through contaminated foods, mainly targets the liver, brain, and kidneys. Most outbreaks are found in Indonesia and China, but the largest outbreak occurred in 2016 in Mozambique among attendees at a funeral who drank traditionally brewed pombe beer (a traditional fermented beverage made of sorghum, bran, corn, and sugar that is fermented with Schizosaccharomyces pombe yeast). A total of 230 were poisoned, and 75 people died.

Table 10. Mass Poisoning Due to Contamination with Bongkrekic Acid

Recreational exposures associated with mass poisoning

Methanol. Methanol poisoning can be unintentional to the person ingesting it (eg, with adulteration), or it can be intentional (eg, as a misguided attempt to ingest an intoxicating substance, or less commonly as an agent of suicide or murder). In some cases, categorizing the nature of the ingestion is problematic. In this section, we consider all cases of methanol poisoning resulting from drinking surrogate alcohol with a recreational intent.

Surrogate alcohol is a term for a product containing ethanol that is not meant for human consumption but is nevertheless intentionally consumed by humans. Consumption of surrogate alcohol may carry extreme health risks from toxic substances that may be present (eg, methanol or lead). Often those who seek out surrogate alcohol are either underaged, unable to afford consumable alcoholic beverages (eg, homeless alcoholics), or have no immediate access to drinking ethanol (eg, prison inmates and individuals in psychiatric wards).

Table 11. Recreational Mass Poisoning with Neurotoxic Poisons (Methanol)

Although Iranian outbreaks of methanol poisoning were not new in 2020, their magnitude was nevertheless unprecedented and stemmed in part from internet claims that alcohol or methanol specifically could cure COVID-19. The Iranian government mandates that manufacturers of methanol add an artificial color to their products so the public can distinguish it from ethanol. Ethanol production is illegal in Iran. Some Iranian bootleggers add bleach to methanol to remove the added color before selling it as drinkable. Methanol is also used to adulterate traditionally fermented alcohol. All the methanol outbreaks for which data were available are listed above, rather than separating them and considering some as instances of adulteration. There have been numerous reports from Iran concerning the epidemic in 2020, but the documentation is poor, many reports consider “alcohol poisoning” without identifying how many actually had methanol toxicity, and many reports present overlapping or partially overlapping data, either spatially or temporally or both.

Non-terrorism mass murder by poisoning

Many examples of non-terrorism mass murder by mass poisoning were serial poisonings over a period of years by individuals who were medical professionals (ie, a nurse, midwife, or physician) (Bodó 2002a, 2002b; 152; 01; 192). An exception was the mass murders and mass “suicides” ordered of cult members at Jonestown, Guyana, in 1978 (see below). Another exception was a fast-food proprietor, who poisoned his competitor's breakfast snacks with the rodenticide tetramine, causing more than 340 poisonings and 42 deaths, all around September 14, 2002.

Table 12. Non-Terrorism Mass Murder by Poisoning with Neurotoxic Substances

Cyanide use in the Jonestown massacre (1978). In 1978, the Peoples Temple Agricultural Project, better known by its informal name “Jonestown,” was a remote settlement in Guyana (the small remote country east of Venezuela), established by the Peoples Temple, a San Francisco-based cult under the leadership of “Jim” Jones (James Warren Jones; 1931-1978), who had been a political activist, preacher, and faith healer. On November 18, 1978, Jones orchestrated the deaths of more than 900 people at Jonestown, the nearby airstrip in Port Kaituma, and a Temple-run building in Georgetown, Guyana's capital city. The mass tragedy relied heavily on poisoning with cyanide-laced Flavor Aid, with many followers lining up to drink the lethal poison after being instructed to by cult leader Jones (an event that continues to be reflected in the popular expression of “drinking the Kool-Aid” to refer to a person who believes in a possibly doomed or dangerous idea, although most who employ the phrase seem unaware of its historical origin).

In total, 909 individuals died in Jonestown itself, all but two from apparent cyanide poisoning. Although Jones and some Peoples Temple members referred to “revolutionary suicide” on an audio tape of the event and in prior recorded discussions, at least 70 individuals at Jonestown were injected with poison, apparently against their will, and a third of the victims were minors. Moreover, the poisonings in Jonestown followed the murder of five others ordered by Jones at Port Kaituma, including the assassination of U.S. Congressman Leo Ryan (1925-1978) and murder-suicide ordered by Jones in Georgetown. Furthermore, Jones ordered guards armed with firearms and crossbows to shoot anyone who attempted to flee the settlement. Although some initial press descriptions of the event called it a “mass suicide,” this does not accurately reflect the manner of death for many of the victims; consequently, later sources refer to the deaths as mass murder-suicide, a massacre, or simply mass murder. Mass murder-suicide seems best to describe this atrocity.

Terrorism-related mass poisoning with neurotoxic poisons

Sarin. The nerve agent sarin (isopropyl methylphosphonofluoridate; also known as GB) was originally developed in 1938 in Germany as a pesticide. In its pure form, sarin is a clear, colorless, odorless, and tasteless liquid. Exposure to large doses of sarin may result in loss of consciousness, convulsions, paralysis, and respiratory failure, possibly leading to death. Low or moderate doses of sarin may produce some or all of the following symptoms within seconds to hours of exposure: rhinorrhea, ocular symptoms (eg, lacrimation, miosis, ocular pain, blurred vision), drooling, excessive sweating, respiratory symptoms (eg, cough, chest tightness, tachypnea), abdominal symptoms (eg, diarrhea, nausea, vomiting, abdominal pain), cardiovascular symptoms or signs (eg, bradycardia, tachycardia, hypotension, or hypertension), increased urination, confusion, drowsiness, weakness, and headache.

Sarin was used in two terrorist attacks in Japan in 1994 and 1995 by the cult Aum Shinrikyo, collectively poisoning more than 6000 people and killing 19 (199). After earlier failed attempts at developing and dispersing biological weapons (botulinum toxin and anthrax), the cult tested the development of sarin in a small laboratory beginning in November 1992 and then built a large chemical weapon production facility in the Fujigamine district of Kamikuishiki, labeled Satyan-7 (“Truth”).

The first attack occurred in a residential area of the city of Matsumoto, Japan, on June 27, 1994, when terrorists released about 12 liters of the nerve agent. Approximately 600 residents, rescue staff, and hospital personnel were poisoned; 58 were hospitalized, and seven who lived near the release died before reaching the hospital (inhalation caused instantaneous death by respiratory arrest in four of the victims) (107; 113; 112; 121; 146; 120; 179; 199). The geographical distribution of sarin victims was closely related to the direction of the wind (112). Muscarinic signs were common to all victims, whereas nicotinic signs were only seen in severely affected victims (112). Miosis was the most common sign (120). Laboratory findings for severely poisoned people included decreases in serum cholinesterase and acetylcholinesterase in erythrocytes (107; 173). Mild fever and epileptiform abnormalities on electroencephalogram were present for up to 30 days (107). Examination several weeks after the attack generally revealed no persisting abnormal physical findings in mildly exposed individuals (107), but surviving severely exposed individuals had worse outcomes, including one individual with persistent akinetic mutism 2 years after the attack (173). Acetylcholinesterase returned to normal within 3 months (107). Although subclinical miosis and neuropathy were present 30 days after exposure, almost all symptoms of sarin exposure disappeared rapidly and left no evident sequelae in most mildly exposed people (107).

Three weeks after the intoxication, 129 victims still had some symptoms, such as dysesthesia of the extremities (112). At that time, many victims had begun to experience asthenopia (ocular strain), which was even more frequent at 4 months. Although victims who reported sarin-related symptoms decreased by a year after the attack, some had persistent symptoms (112).

The cult employed a different nerve agent, VX, in late 1994 to assassinate up to 20 dissident members.

The second terrorist attack occurred on March 20, 1995, when cult members released sarin gas on the Tokyo subway, killing 12 and injuring more than 5,500 people, including subway users, subway workers, rescue personnel, and emergency room medical staff (25; 116; 117; 174; 123; 194; 179; 69; 199). Of those who died, two died in station yards, and another 10 died in hospitals within a few hours to 3 months after poisoning (199). Severely poisoned victims who did not immediately die arrived at the emergency department with cardiopulmonary or respiratory arrest with marked miosis and extremely low serum cholinesterase value (118). Common signs and symptoms in less severely poisoned victims included miosis, headache, dyspnea, nausea, ocular pain, blurred vision, vomiting, coughing, muscle weakness, muscle twitching, and agitation (118). Almost all patients showed miosis and related symptoms such as headache, blurred vision, and visual darkness (118).

In general, miosis and copious secretions from the respiratory and gastrointestinal tracts (muscarinic effects) were common in severely to slightly affected victims, whereas weakness and muscle twitches (nicotinic effects) appeared in severely affected victims (199). Leukocytosis and high serum CK levels were common clinical laboratory abnormalities in victims (199).

Ocular signs and symptoms resolved between 3 and 21 days after exposure; treatment with 0.5% tropicamide ophthalmic solution effectively decreased ocular pain (77).

Chronic complications included post-traumatic stress disorder (118; 79; 119; 171), insomnia (78), and neurocognitive impairment (psychomotor function and memory) (70; 115; 102), as well as a variety of nonspecific psychiatric and somatic symptoms (eg, fear or anxiety, headache, fatigue or fatigability, asthenia, shoulder stiffness, asthenopia, and blurred vision) (111; 122; 171). The prevalence of post-traumatic stress disorder was less than 8% after 5 years (199). Neuropathy and ataxia were observed in fewer than 10% of victims, but associated findings generally disappeared between 3 days and 3 months. EEG abnormalities persisted for up to 5 years (199). Other subclinical effects were evident in the central and autonomic nervous systems of survivors for months after the attack (109).

Oximes, atropine sulphate, diazepam, and ample intravenous infusion were effective treatments (199). Intravenous pralidoxime iodide reversed cholinesterase and symptoms quickly, even if administered 6 hours after exposure (199).

Table 13. Use of Neurotoxic Poisons in Terrorism

War crimes using neurotoxic agents for mass poisoning

The largest use of chemical weapon nerve agents in war was by Iraq in the Iran-Iraq War (1980-1988). Iraq used two nerve agents in the G series: GA or tabun (EA1205) and GB or sarin (EA1208). G-series nerve agents are a class of chemical warfare agents developed by German scientists before and during World War II. They are organophosphate compounds. The “EA” numbers stand for Edgewood Arsenal number designations for chemical warfare agents. From 1948 to 1975, the U.S. Army Chemical Corps conducted classified human subject research at the Edgewood Arsenal facility in Maryland to evaluate the impact of low-dose chemical warfare agents on military personnel and to test protective clothing, pharmaceuticals, and vaccines.

Iraq's use of nerve agents against Iran in the Iran-Iraq War (1980-1988). Iraq used the nerve gas tabun from 1985 as it faced attacks from Iranian troops and poorly trained but loyal volunteers.

Iraq's use of nerve agents in the Halabja massacre (1988). The Halabja massacre was a massacre of Kurdish people in Halabja in northern Iraq on March 16, 1988, during the closing days of the Iran-Iraq War. Iraqi warplanes and artillery pounded Halabja with mustard gas and the nerve agents sarin and tabun, apparently as punishment because some Kurdish guerrilla forces had joined the Iranian offensive (68). The incident was the largest chemical weapons attack directed against a civilian-populated area in history, killing between 3200 and 5000 people and injuring 7000 to 10,000 more, most of them civilians.

Table 14. Use of Neurotoxic Poisons in War Crimes

Genocide using neurotoxic agents for mass poisoning

Across the various genocides of history, genocide was not commonly implemented by poisoning but rather by forced starvation or execution with bullets, burning, or hanging. However, from 1939 to 1945, the Nazis developed increasingly efficient means of extermination with engine exhaust gas, carbon monoxide, and cyanide. Cyanide and carbon monoxide both bind to cytochrome c oxidase, inhibiting the protein from functioning and leading to the chemical asphyxiation of cells.

The cyanide anion is an inhibitor of the enzyme cytochrome c oxidase (or complex IV, EC 1.9.3.1), a large transmembrane protein complex of the electron transport chain located in the inner membrane of the mitochondria of eukaryotic cells. The cyanide anion attaches to the iron within this protein and prevents the transport of electrons from cytochrome c to oxygen. As a result, the electron transport chain is disrupted, meaning that the cell can no longer aerobically produce ATP for energy. Tissues that depend highly on aerobic respiration, such as the central nervous system and the heart, are particularly affected by this histotoxic hypoxia.

Cyanide use in the Holocaust. Zyklon B (German for Cyclone B) was the trade name of a cyanide-based pesticide invented in Germany in the early 1920s. It consisted of hydrogen cyanide (prussic acid), an eye irritant, and one of several adsorbents (eg, diatomaceous earth).

The product was used by Nazi Germany during the Holocaust to murder approximately 1.1 million people in gas chambers installed at Auschwitz-Birkenau, Majdanek, and other extermination camps. Most of the victims were Jews (although the original tests were done on Russian prisoners of war); by far the majority killed using this method died at Auschwitz. Auschwitz received 23.8 tonnes (23,800 kg), of which 6 tonnes (6000 kg) were used for fumigation (delousing); the remainder of approximately 18 tonnes (18,000 kg) was used in the gas chambers or lost to spoilage (the shelf life was only 3 months).

The gas chambers consisted of a sealed chamber into which a poisonous gas was introduced, usually carbon monoxide or hydrogen cyanide (Zyklon B), both of which specifically inhibit cytochrome c oxidase of the human mitochondrial respiratory chain (09; 43). Despite some pseudo-scientific claims by Holocaust deniers that cyanide was not used to exterminate prisoners, cyanide residuals have been demonstrated on the walls of the gas chambers in the former Auschwitz and Birkenau concentration camps using appropriate forensic methods (94; 60). Residuals of cyanide are also present on the walls of a concrete-walled gas chamber at the former Majdanek concentration camp in the form of the pigment Prussian blue (ferricyanide).

The Nazis started using Zyklon B in extermination camps in early 1942 to murder prisoners during the Holocaust. German SS officer and commandant of the Auschwitz concentration camp Rudolf Hoess (also Höss, Höß, Hoeß; 1901-1947) had been testing and implementing methods to accelerate Hitler's order to systematically exterminate the Jewish population of Nazi-occupied Europe, known as the Final Solution. On the initial suggestion of one of his subordinates, Karl Fritzsch (1903-c1945), deputy and acting commandant at the Auschwitz concentration camp, Hoess introduced the pesticide Zyklon B to be used as the killing agent in the gas chambers. On April 15, 1946, Hoess testified at the International Military Tribunal at Nuremberg, where he gave a detailed accounting of his crimes. On May 25, 1946, Hoess was handed over to Polish authorities, and the Supreme National Tribunal in Poland tried him for murder. Hoess was convicted at his trial in March 1947, and he was sentenced to death by hanging, which was carried out on April 16 next to the crematorium of the former Auschwitz I concentration camp.

Table 15. Genocidal Poisoning with Neurotoxic Agents

Unclassifiable or unclear

Table 16. Unclassifiable Poisoning with Neurotoxic Agents

Esing Bakery Incident or “Ah Lum affair” (1857). The Esing Bakery incident (92; 91) was a food contamination scandal in the early history of British Hong Kong. On January 15, 1857, during the Second Opium War (1856-1860), between 300 and 500 predominantly European residents of the colony were poisoned from bread produced by the Chinese-owned Esing Bakery. Victims fell ill with nausea, vomiting, stomach pain, and dizziness. Later testing concluded that the bread had been adulterated with large amounts of arsenic trioxide. There were no deaths immediately attributable to the poisoning, although three deaths that occurred the following year were ascribed to the long-term effects of arsenic poisoning. The quantity of arsenic involved was thought to be so high that the poison was vomited out before it could be fatally absorbed. A total of 52 Chinese men were detained and examined at the Central Police Station on January 21. The proprietor, Cheong Ah-lum (alternate transliterations of his name include Cheung instead of Cheong and A[-]lum, Allum, Ahlum, or Ah Lum instead of Ah-lum), was accused of plotting the poisoning but was acquitted in a jury trial. Despite this, Cheong was successfully sued for damages and was banished from the colony.

Responsibility for the incident and its intention remain matters of debate; proposed explanations include accidental contamination or intended murder for either commercial sabotage, terrorism, or a war crime orchestrated by the Qing government. Chemical analyses at the time do not support an accidental cause because arsenic was found only in the bread itself, and in massive quantities, but not in the flour, yeast, pastry, or scrapings collected from the table. The poison must have been introduced shortly before baking. Moreover, the decision to poison European-style bread, which was generally not eaten then by the Chinese, served to target European victims with a readily available and fast-acting poison.