CHAPTER 13TERRORISM, TOXICITY, AND VULNERABILITY: CHEMISTRY IN DEFENSE OF HUMAN WELFARE

From Green Chemistry and the Ten Commandments of Sustainability, Stanley E. Manahan, ChemChar Research,

Inc., 2006manahans@missouri.edu

13.1. VULNERABILITY TO TERRORIST ATTACKChemicals harming people in terrorist attacks and accidents• Explosive mixture of ammonium nitrate (a common agricultural

fertilizer) and diesel in the attack on the Alfred P. Murrah Oklahoma City Federal Building in 1995

• Explosives used by suicide bombers in the Middle East• Methyl isocyanate in the industrial chemical accident in Bhopal,

India, in 1984• Almost 200 killed by hydrogen sulfide in natural gas released

Chuandongbei natural gas field of southwestern China in December, 2003

Environment susceptible to terrorist attack

Protection With Green ChemistryGreen chemistry to mitigate terrorist threats• Uses the safest possible chemicals as safely as possible• Minimizes the accumulation of hazardous chemicals and

eliminates hazardous chemical wastes• Better detection of hazardous materials• Effective substitute materials to reduce potential for “resource

blackmail”• Sustainable energy sources to reduce “energy blackmail” such as

supplies of petroleum and natural gas• Biochemistry and recombinant DNA science to enable the

development of better vaccines against pathogenic biological warfare agents and antidotes to chemical and biological toxins

13.2. PROTECTING THE ANTHROSPHEREInfrastructure• Water purification and delivery• Electricity generation and distribution• Transportation infrastructureVulnerability due to interconnectivity• Failure of electrical gridsCascading failures on complex networks that operate “close to the edge” so that a relatively small failure can rapidly cascade into a major failure• Electrical grids •Internet systems • “Just in time” manufacturingChemistry can be applied to infrastructure protection• Example: Production of materials that resist heat and flame

13.3. SUBSTANCES THAT EXPLODE, BURN, OR REACT VIOLENTLY

Explosives

Nitroglycerin 2,4,6-Trinitrotoluene (TNT)

C

C

C

H

H

H

H

H

ONO2

ONO2

ONO2

C

H

HC

H

H

H

H

ONO2

H

ONO2

H

C

C

C

ONO2O2NO

CH3

NO2

NO2

O2N

N

N

NNO2

NO2

O2N

1,3,5-Trinitro-1,3,5- Pentaerythritoltriazacyclohexane (RDX) tetranitrate (PETN)

Hazardous Substances (Cont.)Flammable fuels and solventsCorrosive substances• Sulfuric acidHazardous substances widely used in industryPractice of industrial ecology and green chemistry minimizes threats, producing and using hazardous substances• In minimal quantities• Where needed• As needed, “just-in-time”

13.4. TOXIC SUBSTANCES AND TOXICOLOGYTable 13.1. Major Target Systems of Toxic Substances

Respiratory system Emphysema from cigarette smoke, lung cancer from asbestos

Skin responses Allergic contact dermatitis, such as from exposure to dichromate; chloracne from exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (“dioxin”); skin cancer from exposure to coal tar constituents

Hepatotoxicity (toxic effects)

Steatosis (fatty liver), such as from exposure to carbon tetrachloride cirrhosis; (deposition and buildup of fibrous collagen tissue) from excessive ingestion of ethanol; haemangiosarcoma, a type of liver cancer observed in workers heavily exposed to vinyl chloride in PVC plastic manufacture

Reproductive system Interference with sperm development by some industrial chemicals, interference with cells involved with egg formation by chemicals such as cyclophosphamide

Target system Typical toxic responses

Blood Carboxyhemoglobin formation from binding of carbon monoxide to blood hemoglobin, methemoglobinemia consisting of conversion of iron(II) to iron(III) in hemoglobin from exposure to substances such as aniline or nitrobenzene, aplastic anemia from exposure to benzene

Immune system effects Immunosuppression from exposure to radiation, hypersensitivity from exposure to beryllium

Endocrine system effects Disruption of endocrine function by endocrine disruptors such as bisphenol-A

Nervous system Encephelopathy (brain disorder), such as from exposure to lead; peripheral neuropathy from exposure to organic solvents; inhibition of acetylcholinesterase enzyme in nerve function by exposure to organophosphate military poisons

Kidney and urinary tract system

Nephrotoxicity to the kidney by heavy metal cadmium

Table 13.1. Major Target Systems of Toxic Substances (Cont.)

* LD50 values are in units of mg of toxicant per kg of body mass.

Puffer fish toxin#

Relative ToxicitiesRelative Toxicities–––––––––––––––––––––

105104105431052101

1. Practically nontoxicDEHPEthanolSodium chlorideMalathionChlordaneHeptachlorParathionTEPPTetrodotoxinTCDD5Botulinus toxin

3. Moderately toxic, 500 to 5000 mg/kg10-110-210-310-410-5

> 1.5 × 104 /mg kg2. , 5 Slightly toxic× 103 1.5 to× 104 /mg kg Substance Approximate LD50* T oxicity rating

4. V , 50 ery toxic to 500 /mg kg5. ,Extremely toxic 5 50 /to mg kg6. ,Supertoxic < 5 /mg kg Inland taipan venom#

Relative Toxicities of Insecticidal Parathion and Nerve Gas Sarin

Metabolism of Toxic SubstancesXenobiotic substances are those that are normally foreign to living systemsXenobiotic substances, are subject to metabolic processes• Activate to more toxic substance• Convert to less toxic substance (detoxication)Two phases of metabolism of toxic substancesPhase I reactions normally consist of attachment of a functional group, usually accompanied by oxidationPhase II reactions consist of binding to an endogenous conjugating agent, typically glucuronide

Phase I Reactions

Most Phase I reactions are microsomal mixed-function oxidaseReactions• Catalyzed by the cytochrome P-450 enzyme system• Associated with cell endoplasmic reticulum• Occurring most abundantly in the liver of vertebrates

Phase II ReactionsCOOCarboxyl:OHHydroxyl:F,Cl,Br,IHalogen:NHHAmino::EpoxideCCOConjugationproduct

EndogenousconjugatingagentFunctional groups that reactwith a conjugating agentXenobioticcompound,often Phase1 reactionproduct

+

• More easilyeliminated• Greater water solubility• Higher polarityGlucuronide conjugate

HOOOOHOHOHXRC

Phase I and Phase II Reactions and ToxicityIn some cases, Phase I and Phase II reactions make substances toxic or more toxic• Most human carcinogens are produced metabolically from non-

carcinogenic precursors

Dynamic Phase of Toxicity

13.5. TOXIC CHEMICAL ATTACKBhopalAccidental release of methyl isocyanate from a chemical manufacturing operation in Bhopal, India, during the night of December 2/3, 1984 illustrates potential for terrorist attack

Methyl isocyanateC NH

H

H

C O

• About 40 tons of methyl isocyanate was released exposing thousands

• More than 3000 died, primarily from pulmonary edema (fluid accumulation in the lung)

• Immunological, neurological, ophthalmic (eye), and hematological effects

Methyl isocyanate is the most toxic of the isocyanates• High vapor pressure • Toxicity to multiple organs• Cross cell membranes • Reach organs far from exposure site

Potential Chemical AgentsCarbon monoxide• Has killed thousands accidentally and by suicide• Odorless, no warning

+ O2NNNNFe2+HemoglobinmoleculeHb O2HbNNNNFe2+HemoglobinmoleculeO2

Carbon monoxide binding with hemoglobin:

O2Hb + CO COHb + O2 (13.5.1)Effects• 10 ppm: Impaired visual perception and judgment• 100 ppm: Dizziness, headache, and fatigue• 250 ppm: Unconsciousness • 1000 ppm: Rapid death

Potential Terrorist Agents (Cont.)

Chlorine (Cl2)Widely usedFirst military poison in World War IStrong oxidizer that forms acids and is especially damaging to respiratory tissue• 10-20 ppm: Acute respiratory tract discomfort• 1000 ppm: Rapidly fatalHydrogen cyanide, HCN, is a highly toxic gaseous substance with potential for attack through the atmosphere• Also toxic as salts, such as KCN (potential attack through food and

water)

Cyanide binds with iron in the +3 oxidation state of ferricytochrome oxidase enzyme preventing utilization of O2 leading to rapid death• Antidote is to form iron in the +3 oxidation state from blood

hemoglobin to produce methemoglobin that binds with cyanide

Potential Terrorist Agents (Cont.)

Hydrogen sulfide, H2S• Colorless gas with a foul, rotten-egg odor• As toxic as hydrogen cyanide and may kill even more rapidly• 1000 ppm: Rapid death from respiratory system paralysis• Nonfatal doses can cause excitement due to damage to the central

nervous system; headache and dizziness may be symptoms of exposure

Military PoisonsMustard oil, bis(2-chloroethyl)sulfide:

Mustard oil

ClC

H

HH

H

CC

H

HH

H

C SCl

• Vapors penetrate rapidly and deeply into tissue• Tissue damage and destruction well below the point of entry• Blistering gas producing severely inflamed lesions that are

susceptible to infection• Likely to be fatal in lungs• Mutagen and possible carcinogen

Nerve GasesNerve gas organophosphates are the military poisons of most concern

H C P FOH

HO

CC CH

H

H H H

H

HP CO

NNH

HCH

H

H

H

CO

H CC

H H

H

H

H3C CH3C

H

O

O FP

O

H

C CH3H3C

Sarin Tabun Diisopropylphosphofluoridate

Sarin• Tokyo subway attack• Fatal at a dose of only about 0.01 milligrams of Sarin per kilogram

of body mass• Single drop through the skin can kill a human

Action of Organophosphate PoisonsOrganophosphate military poisons act on the nervous system by binding with and inhibiting acetylcholinesterase enzyme

Inhibited enzyme+H3CNCNCHHOHOHH CNCNOHHHHCHCCH3H3COHCH3CH3COOP

Serine side-chain onenzyme active sitePOOCCH3CH3HOH3CCHCFDiisopropylphospho-fluoridate(13.5.2)

Toxins from Biological SourcesBiotoxins• Some of the most toxic substances knownBotulinum toxin• From Clostridium botulinum bacteria growing in the absence of

oxygen• As little as 1 millionth of a gram can be fatal to a human• In principle, millions of people could be killed by the amount of

botulinum toxin carried in a terrorist’s pocket• Binds with nerve terminals causing paralysis of the respiratory

muscles and death

Ricin BiotoxinRicin• Very stable proteinaceous material extracted from castor beans

(Ricinus communis)• Injection of an amount about the size of a pinhead can be fatal• Failure of kidneys, liver, and spleen along with massive blood loss

from the digestive tract• Hazard lessened by need to inject

13.6. PROTECTING WATER, FOOD, AND AIRChemical attack on food supply at a sufficient scale to cause many poisonings is not likelyAttack on food supply by microorganisms• Anthrax bacteria through air or contact, such as through mail• Shigella dysenteriae bacteria on food can cause severe dysentery• Salmonella bacteria in contaminated food can cause debilitating

digestive tract effects• Although usually not fatal, Salmonella on food have the potential

to cause temporary disability

Protection of Water SuppliesCentral distribution to large numbers of peopleSusceptible to both chemical and biological attack, though such an attack would be difficultArsenic in Bangladesh well water shows potential of chemical attackA small amount of botulinus toxin in water could kill manyMicroorganism contamination of drinking water• Millions have been killed by waterborne cholera, typhoid, and

dysentery• In 1993, more than 400,000 people in Milwaukee were sickened

and over 50 died from waterborne protozoal Cryptosporidium parvum

• In May, 2000, approximately 3000 people were made ill and seven died in Walkerton, Ontario, Canada, from drinking water contaminated with Escherichia coli bacteria that produced shiga toxin by transfer of DNA from Shigella dysenteriae bacteria

• Bacteria that could be added deliberately to drinking water include Shigella dysenteriae, Vibrio cholerae, and Yersinia pestis.

Attack Through The AtmosphereAtmosphere as a medium for chemical attack• Means of delivery, such as a low-flying crop-spraying plane would

give warningAtmosphere as a medium for biological attack• Anthrax spores from Bacillus anthracis are a particular concern• Variola major, which causes smallpox• Francisella tularensis, which causes tularemia• Viruses that cause viral hemorrhagic fevers, including Ebola,

Marburg, Lassa, and Machupo• Bubonic plague caused by Yersinia pestis bacteria that killed tens

of millions during the Middle Ages

13.7. DETECTING HAZARDSExplosives• Residues of TNT, RDX, and PETN explosives detected by

sophisticated instruments including ion mobility spectrometers and chemiluminecence sensors

• Nuclear quadrupole resonance (NQR) may be useful to detect explosives because it responds to nitrogen, which all major explosives contain

• Canine olfactory detection (dog’s nose)

13.8. GREEN CHEMISTRY TO COMBAT TERRORISMSafe and sustainable green chemistry can help combat terrorism• Hazardous substances that might be stolen or diverted for use in

attacks are not made or used in large quantities• Chemical products do what they are supposed to do and are used in

minimum quantities• Materials and processes that are likely to result in violent reactions,

fires, high pressures, and other extreme conditions are avoided• Potentially hazardous auxiliary substances and flammable

materials are avoided• Minimizes energy consumption, thereby reducing energetic, high-

temperature processes that might be susceptible to sabotage

Green Chemistry to Combat Terrorism• Biological processes used in green chemistry are carried out under

the mild, low temperature, toxic-substance-free, inherently less hazardous conditions conducive to biochemical reactions

• Reduces demand on uncertain sources of energy and raw materials controlled by potentially hostile populations that are inherently subject to disruption and blackmail

The practice of green chemistry requires exacting process control combined with real-time, in-process monitoring techniques • Conditions that resist sabotage• Passive safety systems that function by default in the event of

failure of or deliberate damage to intricate control systems• Example: Making methyl isocyanate on site as needed

13.9. GREEN CHEMISTRY FOR SUSTAINABLE PROSPERITY AND A SAFER WORLD

Reducing poverty, human misery, and hopelessness helps alleviate conditions that promote terrorismPeople with satisfied material needs able to lead comfortable and fulfilling lives are relatively less likely to commit violent acts

Prosperity, narrowly defined, has resulted in consumption of increasingly scarce resources and environmental degradation

• Quote: “We are past the days when we can trade environmental contamination for economic prosperity; that is only a temporary bargain, and the cost of pollution both economically and on human health is too high.”

• Green chemistry fulfills human needs and makes life more comfortable

Green chemistry and the practice of industrial ecology can provide high living standards sustainably

Abundant, Inexpensive, Sustainable Energy is Key

Energy (Cont.)Problems with energy• Energy sources tend to be contentious and competition for them

has precipitated past wars• Some major regions of petroleum of petroleum production are

breeding grounds for terrorists. The provision of adequate energy independent of such sources would substantially reduce terrorist threats.

Abundant, sustainable energy can lead to less terror-prone societies• Production of food through synthesis of fertilizers (particularly by

synthetic fixation of atmospheric nitrogen) and for irrigation, cultivation, and reclamation of farmland

• Fabricate materials for housing and provide the heating, cooling, and lighting required to make dwellings comfortable

• Pump water from abundant sources to more arid regions• Purify marginal sources of water and reclaim water after use• Desalinate water• Provide safe, comfortable, non-polluting transportation systems

Energy (Cont.)Abundant, sustainable energy requires the best practice of green chemistry, green engineering, and industrial ecology• Increased efficiency of energy utilization is a key aspect of

providing more usable energy• Solar, wind, and biomass energy are sustainable, renewable energy

sources• Fossil fuels will play an interim role, especially if sequestration of

greenhouse gas carbon dioxide byproduct can be achieved• Nuclear fission with uranium fuel can provide abundant energy

safely with new-generation nuclear reactors and reprocessing of nuclear fuel.

Energy (Cont.)Because wind and solar sources are by nature intermittent and dispersed and often produce electricity in locations far from where it is used, storage and transport of energy are very important• Superconductor or quantum conductor power cables are candidates

for transport of electrical energy from source to use• Pumped water hydroelectric storage or high-speed flywheels

coupled with electric motor/generators

• Elemental hydrogen, H2, will be widely used for energy storage and transport as well as for fuel, moved by pipeline and used to produce electricity directly in fuel cells

• Hydrogen from electrolysis of water• Direct photoconversion of water to hydrogen and oxygen may

eventually become practical