Mammalian acute and prolonged toxicity of vesicants has been studied extensively providing a number of data on mechanisms of toxicity and toxicological end points (Watson and Griffin 1992; Ghabili et al. 2010; Razavi et al. 2012; Graham and Schoneboom 2013). Vesicants, but also their degradation products, are extremely toxic for terrestrial mammals. Reviewing the toxicological end points of vesicants Munro et al. (1999) collected the data on median lethal doses (concentrations, carcinogenicity, genotoxicity, reproductive, systemic and other relevant effects of mustards and lewisite derivatives. HN1 and SM as typical alkylating agents as well as their degradation products have been shown to be mutagenic in a wide variety of species (Fox and Scott 1980). International Agency for Research on Cancer (IARC) has classified sulfur mustard as “carcinogenic to humans” (Group 1) based on sufficient evidence in humans (ATSDR 2003; Wulf et al. 1985).

The toxic military material, often dumped in sea waters worldwide, represents a serious potential threat to the marine environment. Vesicants are toxic to all aquatic species, however, their toxic effect is limited by their low water solubility. Toxicity of degradation products is generally lower than the toxicity of parent compounds. Estimated lethal concentration of SM in fish amounted in the range of 25–50 μg/L, whereas after chronic (30 – day) exposure of bluegill sunfish (Lepomis macrochirus), red-eared sunfish (Lepomis microlophus) and black bullheads (Ameiurus melas) toxicity threshold was assessed at 2 mg/L (Munro et al. 1999). Although difficult to make direct comparisons of test results, it seems that nitrogen mustards were less toxic than sulfur mustard for aquatic organisms. Chronic toxicity threshold values of nitrogen mustards with black bullheads were at least four times higher (HN1 – 25 mg/L, HN2 – 10 mg/L, HN3 – 8 mg/L) than the value of sulfur mustard obtained for the same exposure duration (30 days). Acute toxicity tests of HN2 performed for invertebrata Ceriodaphnia dubia and Daphnia magna after 48 h exposure resulted in LC₅₀ of 1.12 and 2.52 mg/L, respectively, and LC₅₀ of 98.86 mg/L for the fish species Pimephelas promelas obtained after 96 h exposure (Lan et al. 2005). Based on these data it can be concluded that HN2 is toxic for invertebrata and harmful for fish species. Chronic toxicity tests related to survival and reproduction effect of HN2 showed the dissimilar susceptibility of the species with the no observed effect concentrations (NOECs) of 0.0039 and 2.5 mg/L for Ceriodaphnia dubia and Pimephelas promelas, respectively. The clear difference in toxicity between species is attributed to the ability of more complex organisms, such as fish, to detoxify HN2.

In 30 – day tests, the thresholds for lethality of lewisite for two aquatic organisms were 0.2 mg/L (black bullheads) and 0.5 mg/L (bluegill sunfish), indicating much higher toxicity in relation to mustard agents (Munro et al. 1999).

In 2005, within the EU the Sixth Framework Programme project (FP6), a project Modeling of Ecological Risks Related to Sea-dumped Chemical Weapons (MERCW) was launched to evaluate overall chemical war agents (CWA) risks in the Baltic Sea and also to identify uncertainties and future needs. Data on ecotoxicological risk have been expressed in toxic units (TU), which represent the ratio between the exposure concentration and fish no observed effect concentration (NOEC). Total calculated TU for all nine identified CWAs was 0.62, whereas TU of SM alone was 0.083 (Sanderson et al. 2010), indicating no risk for the model applied in the study. There are no data proving the potential of vesicants to bioconcentrate or biomagnify, due to generally low Kow values (<2) and probably due to their high in vivo reactivity. For example, results of MERCW project have shown that models developed to describe CWAs biomagnification potential in the Baltic commercial fish, including cod (Gadus morhua), herring (Clupea harengus), and sprat (Sprattus sprattus) revealed no such potential of SM.

According to review article of Munro et al. (1999), the nitrogen mustards were less toxic than SM to phytoplankton and higher aquatic plants. At 5 mg/L, Lewisite inhibited the growth of the phytoplankton, and the water milfoil and water crowfoot died; at 50 mg/L, all plants died.

The analysis of the microbial community can be used as an indicator of CWA presence. Some species of microbes are tolerant to hydrolytic products (primarily thiodiglycol) and use these as their sole source of carbon and energy (Medvedeva et al. 2009). But for some other microbiota SM and its hydrolysis products have a broad spectrum of toxic effects reducing thus significantly the near – bottom water heterotrophic microorganism community and species diversity (Sanderson et al. 2010).

Soil contamination with chemicals can exert toxic effects directly to soil organisms, or indirectly, by altering specific interactions and by disrupting the soil food chain. Vesicants may be present in soil for a long time and thus induce the reduction in microbial activity as a consequence of its high toxicity to soil microorganisms. Results of microcosm assay have shown that the EC₅₀ value of sulfur mustard for total numbers of microarthropods was 65 and 130 mg/kg for total numbers of nematodes (Kuperman et al. 2007). The results also suggested that soil constituents, including soil organic matter, can affect the partitioning of sulfur mustard from solid to aqueous phase in soil and thus modify the bioavailability of this chemical to a specific group of the soil invertebrate community.

Throughout history, the toxic properties of certain substances have been applied in armed conflicts. Along with the scientific and industrial progress of a society, the weapons evolved from poisonous darts to fumigants, or rudimentary Chinese chemical grenades to chemical artillery at the beginning of the industrial revolution. Although the use of these toxic substances was sometimes advantageous on the battlefield, the horror and agony of the afflicted echoed in the form of unequivocal public examining and disapproval for many years to come, far outweighing the prospect of using them to temporarily gain the upper hand in war (Mayor 2003).

World War I and the German lethal chlorine gas attack against the Allied Forces at Ypres (April 22, 1915) marked the turning point in the history of chemical warfare. The surprise use of 160 tons of chlorine gas, spread over the French trenches, killing more than 1000 French and Algerian soldiers, and wounding about 4000 more. Whils and effective way of bypassing the trench gunfights and weakening the enemy defenses, WWI led to over 100,000 deaths and a million injuries. (Fitzegerald 2008). Whilst an effective way of bypassing the trench gunfights and weakening the enemy defenses, it led to over 100,000 deaths and a million injuries (Fig. 14.1).

However, this did not stop the major military powers from producing and stockpiling large quantities of chemical arms (200,000 metric tons) after the war, and they had started to become important parts of many armies’ arsenals. Most of them were chlorine, phosgene, diphosgene, chloropicrine, hydrogen cyanide, and vesicants – the first generation of chemical weapons (CW) – as well as tear gases and irritant incapacitants. Over time, mustard, lewisite, as well as their various mixtures, were introduced (propylene mustard, O-mustard, sesquimustard, nitrogen mustard).

After years of effort and peace negotiations, the greatest Allied Forces managed to get the international support to ban the use of CW. The protocol for the prohibition of the use in war of asphyxiating, poisonous or other gases, and of bacteriological methods of warfare, commonly known as the Geneva Protocol, was signed by a number of countries in 1925 and put in motion in 1928. One of the biggest limitations of the protocol was that the countries that had signed it needed only to refrain from using CW first, but not as a counterattack in case they were attacked by one. Additionally, it did not restrict the possession and stockpiling of chemical arms, predict the possibility of sanctions or include a verification mechanism (Hurst et al. 1997; Kenyon 2000; Pitschmann 2014).

The pre-World War II period was marked by the development of new, highly toxic organophosphorus agents in Leverkusen by IG Farben. These compounds represent the second generation of CW. They were used in the conflict between Japan and China in the 1930s, but not during the rest of the WWII (Salem et al. 2008). Following a period of decreased interest in chemical warfare due to the development of nuclear arms, the Geneva Protocol reemerged and was the basis for further resolutions after the use of tear gases and herbicides in the Vietnam War (1961–1973).

The 18th National Committee on Disarmament marked the resumption of the peace negotiations on the chemical arms ban. During the meeting it was agreed that the chemical and biological warfare should be regarded independently. At that time, there was a great divide in the world powers of the West, the countries that were neutral, and the Eastern Bloc, which presented a great hurdle to reaching an agreement. Besides the stockpiles of the USSR and the USA, there were other states as well that were interested in acquiring capacities for CW, including South Africa, some of the Middle East, South Asia, China and the Koreas. Although this was followed by increased preparedness for chemical defense at the state level, civil defense was not in the focus of their interest, as at that time, CW were counted as primarily battlefield weapons. However, as many times before in the history, practice has confuted it.

Bilateral meetings between the USA and the USSR, followed by individual efforts of some countries in negotiations on chemical disarmament, although without significant progress, at least provided important documents, including the draft version of the Convention. In the late 1980s, warming of the relations between the great world powers made it possible to see a global recession from CW as a reality. The use of CW, nerve agents and mustard, in the Iran-Iraq War from 1983 to 1988, also changed the climate in favor of the initiative to ban CW. The UN Secretary-General in March 1984 confirmed in his Report the use of CW, and 1 month later a working paper (CD/500) with the draft CWC was introduced by the USA. Renewed diplomatic process between the Soviet Union and the USA, in the period 1986 to 1991, facilitated the exchange of the detailed information on stockpiles of CW, but also provided a base for the formalized obligation to cease the production of binary CW and controlled destruction of stockpiles.

Confronted with the danger of chemical warfare during the Persian Gulf War, albeit CW were not actually used by Iraq, additionally stimulated negotiators at the Conference on Disarmament to reach the consent on disarmament in September 1992. The draft treaty text of the Convention was submitted to the United Nations and adopted as its Resolution 47/93 (Kenyon 2000).

In 1993, the Convention on the Prohibition of the Development, Production, Stockpiling and Use of Chemical Weapons and their Destruction (CWC) was presented and after a 3 day meeting in Paris, signed by 130 states. The seat of the Organisation for the Prohibition of the Chemical Weapons (OPCW), as it was agreed, would be at the Hague, where the Preparatory Commission would meet and prepare the 1st Session of the Conference of the State Parties (Zanders et al. 1997).

On April 20, 1997, CWC entered into force, and the OPCW began its work providing implementation of the Convention. Up to now, 190 countries have signed the Convention. Israel and Myanmar have not ratified it, and Angola, Egypt, South Sudan and the Korean People’s Democratic Republic have not yet signed (OPCW 2014). From about 71,000 t of declared chemical toxic substances and precursors, more than 72 % had been destroyed by the end of 2012, but the destruction of CW is still not finished, as well as the destruction of old CW. However, one cannot assume that the CW era is history, especially with the increasing potential of their further development using new scientific and technological methods that overlap the field of chemistry and biology, or the continuous research of psychoactive substances. The OPCW is following the scientific achievements, trying to keep abreast of materials and methods that could have implications on CWC (Table 14.2).