Dermatotoxicology of sulfur mustard: Historical perspectives from World War I.

Sulfur mustard has been used as a chemical warfare agent for the past century. After its introduction by the Germans in World War I, investigators quickly began studying its impact on the human body including its deleterious effects on skin. This review focuses on two groups in particular who conducted experiments from 1917 to 1918: the United States Army at the American University Experiment Station Laboratories and Torald Sollmann at Western Reserve University. Through this work, these researchers proved far ahead of their time by anticipating dermatologic phenomena not described in the literature until later in the twentieth century. These include regional variation of percutaneous penetration, effect of vehicle on penetration and predicting immunologic contact urticaria. The work conducted by these researchers set the groundwork for much of twentieth century dermatotoxicology.

Military Importance of Natural Toxins and Their Analogs.

Toxin weapon research, development, production and the ban on its uses is an integral part of international law, with particular attention paid to the protection against these weapons. In spite of this, hazards associated with toxins cannot be completely excluded. Some of these hazards are also pointed out in the present review. The article deals with the characteristics and properties of natural toxins and synthetic analogs potentially constituting the basis of toxin weapons. It briefly describes the history of military research and the use of toxins from distant history up to the present age. With respect to effective disarmament conventions, it mentions certain contemporary concepts of possible toxin applications for military purposes and the protection of public order (suppression of riots); it also briefly refers to the question of terrorism. In addition, it deals with certain traditional as well as modern technologies of the research, synthesis, and use of toxins, which can affect the continuing development of toxin weapons. These are, for example, cases of new toxins from natural sources, their chemical synthesis, production of synthetic analogs, the possibility of using methods of genetic engineering and modern biotechnologies or the possible applications of nanotechnology and certain pharmaceutical methods for the effective transfer of toxins into the organism. The authors evaluate the military importance of toxins based on their comparison with traditional chemical warfare agents. They appeal to the ethics of the scientific work as a principal condition for the prevention of toxin abuse in wars, military conflicts, as well as in non-military attacks.

Poison gas and thefirst World War: key role ofpharmacists.

Poison gas has been the subject of attention from the French army (Grand Quartier General). The 22sd of April 1915, General Joffre decided that the General Direction for Health Service was in charge of the protection of troops against what he called "this new mode of terror, disease, and death". Actions are been launched to found ways for the protection means and to obtain for the army at least equivalent weapons. Pharmacists will have a leading role thanks to their knowledge in chemistry. Research laboratories were working in two areas: individual protection and production of aggressive agents. Paul Lebeau, Gabriel Bertrand, Alexandre Degrez, Charles Moureu were among many others very committed to fight and remains at the top and to react quickly to ennemy's attacks. At the end of the war, Paul Lebeau received the Legion d'Honneur medal for his contribution to war. The school of pharmacy was recognized as faculty of pharmacy, by a decree of May 14th, 1920. The knowledge that were obtained during this period will be used for the second World War, but the chemical weapon was not much used, as opposed to more recent usage in Vietnam, Irak and Syria.

Modern toxic antipersonnel projectiles.

In the spring of 1944, Kurt von Gottberg, the SS police chief in Minsk, was shot and injured by 2 Soviet agents. Although he was only slightly injured, he died 6 hours later. The bullets were hollow and contained a crystalline white powder. They were 4-g bullets, semi-jacketed in cupronickel, containing 28 mg of aconitine. They were later known as akonitinnitratgeschosse. The Sipo (the Nazi security police) then ordered a trial with a 9-mm Parabellum cartridge containing Ditran, an anticholinergic drug with hallucinogenic properties causing intense mental confusion. In later years, QNB was used and given the NATO code BZ (3-quinuclidinyl-benzylate). It was proven that Saddam Hussein had this weapon (agent 15) manufactured and used it against the Kurds. Serbian forces used the same type of weapon in the Bosnian conflict, particularly in Srebrenica.The authors go on to list the Cold War toxic weapons developed by the KGB and the Warsaw pact countries for the discreet elimination of dissidents and proindependence leaders who had taken refuge in the West. These weapons include PSZh-13 launchers, the Troika electronic sequential pistol, and the ingenious 4-S110T captive piston system designed by the engineer Stechkin. Disguised as a cigarette case, it could fire a silent charge of potassium cyanide. This rogues gallery also includes the umbrella rigged to inject a pellet of ricin (or another phytalbumin of similar toxicity, such as abrin or crotin) that was used to assassinate the Bulgarian writer and journalist Georgi Markov on September 7, 1978, in London.During the autopsy, the discovery of a bullet burst into 4 or 5 parts has to make at once suspecting the use of a toxic substance. Toxicological analysis has to look for first and foremost aconitine, cyanide, suxamethonium, Ditran, BZ, or one of the toxic phytalbumins. The use of such complex weapons has to make suspect a powerful organization: army, secret service, terrorism. The existence of the Russian UDAR spray gun in the present day, however, shows that these weapons are still present. The possibility that one might be used to spray a charge of cyanide is still very real, especially as it would not be very difficult for an informed amateur to produce homemade toxic ammunition by adapting existing civil or military cartridges.

[Anniversary of the medical department of the Federal Office for Safe Storage and Destruction of Chemical Weapons].

The article is devoted to the process of formation and development of CW destruction management system and medical support of professional activities of personnel. Founders of Medical department of the Federal Directorate for Safe Storage and Destruction of Chemical Weapons are presented. Main principles and ways of working of medical department in specific conditions are covered.

Challenges faced by British Military Ophthalmic Services during the First World War.

The First World War was a time of great change for many areas of military medicine. This article reviews some of the particular challenges faced by British Ophthalmic Services during 1914-18.

[Sanitary and chemical protection during the Great Patriotic War].

During the Great Patriotic War (1941-1945) there was a real danger of use by German armies of the chemical weapon against staff of Red Army. However German command didn't risked to go on conducting large-scale chemical war against the USSR that rescued from painful death millions person. A principal cause of this decision was well organized and technically provided system of antigas protection in Red Army, including precisely organized actions of sanitary-chemical protection, qualitative preparation of military doctors on these questions and presence at them effective antidotes and other means of treatment of injuries by fighting poison gases.

[First chemical mass attack in history of wars, Bolimów, January 31, 1915]. / Pierwszy masowy atak chemiczny w historii wojen Bolimów, 31 stycznia 1915 R.

World War I was the conflict, during which it was first used chemical warfare on a massive scale. The earliest chemical attack occurred on the Western Front in October 1914 in Neuve Chapelle, but its effects were so minimal that the Allies learned about it only after the war from German documents. The attack in the area Bolimow, made by the Germans against the Russian army with artillery shells containing gas T (xylyl and benzyl bromides), was therefore the first attack on a massive scale recorded on the victim side. The attack, which occurred after it made it possible to obtain some tactical success, but without a strategic breakthrough. Some of the later German attacks on the eastern front where chlorine was used proved to be more effective, but despite the many victims there was not any major strategic success achieved. The Russians did not take attempts to use chemical weapons in the First World War.

The introduction of gas warfare and its medical response in world war one.

The introduction of gas warfare in World War One was impactful, as it both expanded the breadth of warfare and fueled the invention of techniques required to treat these new injuries. Gas injuries were responsible for 91,000 of 1.3 million deaths in World War One. Gassed soldiers had wounds which the world had never seen. They presented in large scale to medical tents and base hospitals across Europe. As gas casualties poured in, doctors and nurses had to treat these conditions in the best way they knew. Gas warfare changed how war was performed and how casualties of this attack were treated. The techniques learned from treating the multitudes of men with gas burns led to advances in the field of burn care, which have helped to improve mortality and reduce morbidity in hospitals across the world.

Choking agents and chlorine gas - History, pathophysiology, clinical effects and treatment.

INTRODUCTION: Choking agent exposure, among them chlorine gas, occurs in household or industrial accidents, chemical warfare and terrorist attacks. AIMS: Review of published animal and human data regarding the history, pathophysiology, clinical effects and management of chlorine exposure. PATHOPHYSIOLOGY: Highly soluble agents cause quick upper respiratory tract symptoms. Chlorine gas has a medium solubility, also causing delayed lower airway symptoms, mainly due to its oxidizing potential by releasing hypochlorous and hydrochloric acid, but also by interacting with Transient Receptor Potential channels. SYMPTOMS: Eyes may show conjunctival injection, abrasions and corrosions. Burns of the oronasal mucosa and trachea can occur. Dyspnea, bronchospasm and possible retrosternal pain occur frequently. Glottis edema or laryngospasm are acute life-threatening emergencies. Chlorine gas can cause toxic pneumonitis, lung edema and acute respiratory distress syndrome (ARDS). MANAGEMENT: General management includes physical examination, pulse oximetry and arterial blood gases. Eyes should be irrigated, humidified oxygen and inhalative bronchodilators administered. An EKG, cardiac enzymes and complete-blood-count should be obtained if there is retrosternal pain. Routine chest x-ray is not recommended - except if pulmonary edema is suspected. Laryngoscopy should be performed if glottis edema is suspected. Sodium bicarbonate inhalation after chlorine gas inhalation is discussed controversially. Mechanical ventilation with continuous-positive-airway-pressure or intubation/tracheotomy with high positive-end-expiratory-pressure may be necessary. Glucocorticoids for prevention of pulmonary edema should be applied restrictively. Prophylactic antibiotics are not recommended. In severe ARDS, extracorporeal membrane oxygenation (ECMO) can be considered. CONCLUSION: Treatment is mainly symptom oriented. New and promising therapies are in development.

The pharmaceutical industry and the German National Socialist Regime: I.G. Farben and pharmacological research.

Before the National Socialist party came to power, the German pharmaceutical industry constituted an international reference as far as the development of new medicines was concerned, having been responsible for synthetic analgesics (phenacetin, phenazones, acetylsalicylic acid), arsphenamine, barbiturates and sulfonamides. The year 1925 saw the founding of I.G. Farben (Interessen-Gemeinschaft Farbenindustrie AG), a conglomerate of companies that would monopolize the country's chemical production and come to own all its major pharmaceutical industries. During the World War II, I.G. Farben participated in numerous operations associated with the criminal activities of the Nazi executive, including the use of slave labour in plants built close to concentration camps, such as that at Auschwitz. With regard to medical and pharmacological research projects, I.G. Farben became involved in experimental programmes using patients from the Nazi regime's euthanasia programmes and healthy subjects recruited without their consent from concentration camps, on whom various pharmacological substances were tested, including sulfamide and arsenical derivatives and other preparations whose composition is not precisely known (B-1012, B-1034, 3382 or Rutenol, 3582 or Acridine), generally in relation to the treatment of infectious diseases, such as typhus, erysipelas, scarlet fever or paratyphoid diarrhoea. Furthermore, I.G. Farben played a decisive role in the German army's chemical warfare programme, contributing to the development of the first two neurotoxic substances, later known as 'nerve agents', tabun and sarin. Some of these activities came to light as a result of the one the famous Nuremberg Trials in 1947, which saw 24 executives and scientists from I.G. Farben brought to justice for, among other offences, the use of slave labour in the concentration camps and forced experimentation with drugs on prisoners.

Military chemical warfare agent human subjects testing: part 1--history of six-decades of military experiments with chemical warfare agents.

Military chemical warfare agent testing from World War I to 1975 produced thousands of veterans with concerns of possible long-term health consequences. Clinical and research evaluation of potential long-term health effects has been difficult because the exposures occurred decades ago, the identity of troops exposed and exposure magnitudes are uncertain, and acute effects during experiments poorly documented. In contrast, a companion article describes the large amount of information available about the specific agents tested and their long-term health effects. This short history describes U.S. military chemical-agent experiments with human subjects and identifies tested agents. Finally, the demonstrated need to anticipate future health concerns from military personnel involved in such military testing suggests current and future military researchers should be required, by law and regulation, to fully record the identity of those exposed, relevant exposure magnitude, and complete medical information for all subjects. New study protocols and institutional review board approvals for research involving military personnel should reflect this need.

Military chemical warfare agent human subjects testing: part 2--long-term health effects among participants of U.S. military chemical warfare agent testing.

Military chemical warfare agent testing from World War I to 1975 produced thousands of veterans with concerns about how their participation affected their health. A companion article describes the history of these experiments, and how the lack of clinical data hampers evaluation of long-term health consequences. Conversely, much information is available about specific agents tested and their long-term health effects in other populations, which may be invaluable for helping clinicians respond effectively to the health care and other needs of affected veterans. The following review describes tested agents and their known long-term health consequences. Although hundreds of chemicals were tested, they fall into only about a half-dozen pharmaceutical classes, including common pharmaceuticals; anticholinesterase agents including military nerve agents and pesticides; anticholinergic glycolic acid esters such as atropine; acetylcholine reactivators such as 2-PAM; psychoactive compounds including cannabinoids, phencyclidine, and LSD; and irritants including tear gas and riot control agents.

Phosgene use in World War 1 and early evaluations of pathophysiology.

World War 1 ended 100 years ago. The aftermath included the consolidation of significant advances in medical care of casualties. Some of these advances were made in the care of chemical casualties, in particular the mechanisms of toxicity and treatment of phosgene exposure. Phosgene, or carbonyl chloride, is an extremely poisonous vapour that was used to devastating effect during World War 1. Observations made of acutely poisoned casualties formed the basis of much research in the early post-World War 1 era. Some extremely elegant experiments, some at the nascent Porton Down research facility, further evaluated the toxin and defences against it. Researchers drew on knowledge that was later forgotten and has since been relearnt later in the 20th century and made many correct assumptions. Their work is the bedrock of our understanding of phosgene toxicity that survives to this day. The horrors of chemical warfare prompted the Geneva Protocol of 1925, prohibiting the use of chemical agents in warfare, and chemical warfare on this scale has not been repeated. The ease with which phosgene can be synthesised requires healthcare providers to be familiar with its effects.

Mass casualty chemical exposure and implications for respiratory failure.

Exposure to chemical agents, both deliberate and accidental, over the past 100 years has resulted in the deaths of thousands and a significant number of casualties requiring hospitalization. The respiratory system is an important portal of entry into the human body for many of these agents, and pulmonary symptoms are a hallmark of many chemical exposures. The 4 major chemical warfare agents are: lung-damaging, blood, blister, and nerve compounds. The review will cover historical exposures, signs and symptoms, treatment, and long-term consequences. There are numerous examples of deliberate (as well as accidental) exposure to harmful chemicals, and each incident requires the provider to understand the signs and symptoms of the particular chemical so that the correct treatment is provided. The respiratory implications of these agents appear to be dose and timing dependent, with full recovery often seen if supportive measures and appropriate antidotes are administered in a timely fashion.

Mustard gas and American race-based human experimentation in World War II.

This essay examines the risks of racialized science as revealed in the American mustard gas experiments of World War II. In a climate of contested beliefs over the existence and meanings of racial differences, medical researchers examined the bodies of Japanese American, African American, and Puerto Rican soldiers for evidence of how they differed from whites.

Chemical warfare agent NOVICHOK - mini-review of available data.

The Cold War period is characterized by the infighting between the Western countries and the USSR in diverse areas. One of such fields was development of the weapons of mass destruction. Within various programs on both sides, a wide scale of different agents have been developed. However, information about some of them are still protected under the designation "top secret". Notwithstanding, in history several cases are known when such information beheld the daylight. One of such cases was the program FOLIANT and NOVICHOK. Both programs were developed by the USSR as a reaction to English/American invention of VX agent. If at least a part of available information is truthful, we can allege that these compounds belong among the most toxic synthetic agents ever. Within this contribution, we have reviewed available Eastern and Western data about the A-agents and their precursors, so-called NOVICHOKs, including their history, synthesis, physical-chemical properties, pharmacological characteristics and clinical manifestation.