Chemical Warfare Agents Radiotoxicology lecture from Toxicology 15. 12. 2020 Marta Chalupová Chemical Warfare History • poisons used as weapons in warfare • large scale use of toxic chemicals as weapons occurred during the World War I (1914 -1918) – German chlorine gas attack in Flanders on April 1915 – yperite used in 1917 by German army near Ypres in France Chemical Warfare History • World War II (1938 -1945) – Zyklon B – from 1941 used in gas chambers Chemical Warfare History • Vietnam War (1961 -1971) – widespread use of chemical defoliants and herbicides – distributed in drums marked with color-coded bands (Agent Pink, Agent Green, Agent Purple, Agent Blue, Agent White, Agent Orange) Tokyo Sarin Attack • March 20 1995, Tokyo underground • religious sect Aum Shinrikyo with the leader Shoko Asahara • 12 people died Moscow Theater Hostage Crisis • 23 October 2002 Dubrovka Theater in Moscow • Chechens islamists took 850 hostages and after a two-and-a-half day siege they pumped maybe fentanyl into the ventilation • 129 of hostages were killed Chemical Warfare NERVE AGENTS BLISTER AGENTS (VESICANTS) CHOKING AGENTS (LUNG IRRITANTS) INCAPACITATING AGENTS (HALLUCINOGENS) BLOOD AGENTS TEAR GAS (EYE IRRITANTS) BIOLOGICAL WARFARE AGENTS Nerve Agents Organophosphates • sarin, soman, tabun • highly lipophilic compounds taken up by ingestion, inhalation and through the skin • inhibition of acetylcholinesterase (AChE) • peripheral muscarinic stimulation of exocrine glands and smooth muscles • respiratory paralysis with bronchorrhea and bronchospasm • epileptiform stimulation with seizures • treatment: atropine, diazepam, oximes Alkylating Blister Agents (Vesicants) • sulfur and nitrogen mustards (compounds with chloroethyl groups) • slowly evaporating liquids with a strong odor (garlic, fish) • highly reactive, lipophilic compounds taken up by ingestion, inhalation and through the skin • symptom-free interval of several hours, the maximum after 3–4 days • skin: itching, redness, blistering, necrosis • systemic toxicity due to alkylation of DNA (potential cancer causing agent) • treatment: skin cooling, sterile dressings Arsenic-Containing Vesicants LEWISITE • lipophilic substance taken up by ingestion, inhalation and through the skin • wide range of symptoms • eyes – irritation, blepharospasm, erosion • airways – irritation, cough, toxic pulmonary edema • GIT – nausea, vomiting, diarrhea • skin – irritation, burning, redness, swelling, blistering, necrosis Choking Agents (Lung Irritants) • poisons that damage the lungs such as phosgene (COCl2), chlorine gas (Cl2), chloropicrin • major role as choking agents in WWI • lead to choking and toxic lung edema Choking Agents (Lung Irritants) PHOSGENE • smell range from decaying fruit to fresh cut grass or mouldy hay • irritation of eyes, nose and throat, chest tightness occur rapidly followed by shortness of breath and coughing • the dose greater than 30 ppm a minute leads to severe lung damage and fatal lung edema • at high concentrations, individuals lose their sense of smell and their ability to assess danger Psychically Incapacitating Agents • 3-quinuclidinyl benzilate (BZ), hallucinogens (atropine, scopolamine, LSD, hyoscyamine) • lead to the production of temporary mental efects that will render individuals incapable of concerted effort • disturbances in level of consciousness • poor judgment and insight • stupor, confusion, confabulation • hallucinations, ilusions Blood Agents Hydrogen cyanide (HCN) • high toxicity by inhalation or ingestion • high vapor pressure at room temperature • immediate effect – stops cellular respiration by inhibiting an enzyme cytochrome c oxidase in mitochondria • concentration of 3500 ppm (about 3200 mg/m3) will kill a human in about 1 minute • chemical weapon in WWI • used as Zyklon B in gas chambers during WWII Eye Irritants (Tear Gases) • chloroacetophenone, chlorobenzylidene malononitrile • used for self-defence and riot control • primarily taken up by inhalation • mechanism of action have not been estabilished • intense stimulation of the mucosae (eyes, nasopharynx) • high concentrations cause headache, nausea and toxic pulmonary edema Biological Warfare Agents • specific application devices (bomb, letter bomb, poisoning of water supply) that release biological agents – living organisms (bacteria, viruses, fungi) or their toxins • usually release of odorless and invisible aerosol • fear of bioterrorism • genetic manipulation of pathogens with increased virulence, resistance and stability Biological Warfare Agents • smallpox (variola virus) • anthrax (Bacillus anthracis) • plague (Yersinia pestis) • tularemia (Francisella tularensis) • brucellosis (Brucella species) • encephalitis (viruses) • hemorrhage (viruses) • Botulinum toxin (Clostridium botulinum) • Staphylococcus aureus toxin Radiation Ionizing radiation • high-energy electromagnetic radiation (X-rays, γ-rays) and particulate radiation (α-rays, β-rays, protons, neutrons, heavy ions) • radiation capable for producing ions when interacting with matter – x-rays, alpha, beta, gamma, cosmic rays Nonionizing radiation • short-wave radiation (ultraviolet, laser), radiowaves, microwaves, electric and magnetic fields Biological Effects of Ionizing Radiation Alpha Particles • two neutrons and two protons • charge of +2 • emitted from nucleus of radioactive atoms • transfer energy in very short distances (10 cm in air) • shielded by paper or layer of skin • primary hazard from internal exposure • alpha emitters can accumulate in tissue (bone, kidney, liver, lung, spleen) causing local damage Beta Particles • small electrically charged particles similar to electrons • charge of -1 • ejected from nuclei of radioactive atoms • emitted with various kinetic energies • shielded by wood, body penetration 0.2 to 1.3 cm depending on energy • can cause skin burns or be an internal hazard of ingested Gamma Rays • electromagnetic photons or radiation (identical to X-rays except for source) • emitted from nucleus of radioactive atoms – spontaneous emission • emitted with kinetic energy related to radioactive source • highly penetrating – extensive shielding required • serious external radiation hazard X-rays • overlap with gamma-rays • electromagnetic photons or radiation • produced from orbiting electrons or free electrons – usually machine produced • produced when electrons strike a target material inside and x-ray tube • emitted with various energies & wavelengths • highly penetrating – extensive shielding required • external radiation hazard • discovered in 1895 by Roentgen Radiation • abilities to penetrate matter differ considerably Radiation Half life • rate of decay of radioisotope • how long it takes to lose half their strength • can range from very short to billions of years • carbon – 5730 years, which makes it valuable for dating Reducing exposure • time – reduce the spent near the source of radiation • distance – increase the distance from the source of radiation • shielding – place shielding material between you and the source of radiation Ionizing Radiation Health Effects • we evolved with a certain level of naturally occurring ionizing radiation from cosmic radiation, radioactive materials in the earth • we have mechanisms to repair damage • Exposure – X (J/kg) (Related to energy) • Absorbed Dose – Gray (Gy) (amount of energy absorbed) • Equivalent Dose – Sievert (Sv) (makes different sources of radiation equivalent) Examples of Tissue Sensitivity Very High White blood cells (bone marrow) Intestinal epithelium Reproductive cells High Optic lens epithelium Esophageal epithelium Mucous membranes Medium Brain – glial cells Lung, kidney, liver, thyroid, pancreatic epithelium Low Mature red blood cells Muscle cells Mature bone and cartilage Radioactive Metals Radium (Ra) • isotope 226Ra incorporated into the bones • dissintegrates into the noble gas radon occuring in underground mines • used in spas for treating rheumatism or gout • induce damage to bone marrow (hematopoiesis) – leukopenia, osteosarcoma Radioactive Metals Uranium (U) • isotope 235U used as a nuclear fuel • used as the explosive in the Hiroshima bomb • damage to kidneys (uranium nephritis) and lungs (toxic pulmonary edema) Plutonium (Pu) • isotope 239Pu used in the bomb dropped on Nagasaki • bound in the blood to transferrin • stored primarily in the bone marrow and liver