13. Poisons/Toxins, Hazards chapter 20

Are all chemicals toxic? Yes……..but it depends on the dose!!! Even pure water can kill you (Sacramento Cal. radio station contest Jan 2007) Woman drank ~ 20 : 220mL bottles (ie 4.4 Liters) of pure water in ~ 3 hours , died from electrolyte imbalance Lawsuits pending

A toxin is a harmful substance that has a biological origin. A poison is a substance that can cause illness or death when it enters our bodies. A toxin is a harmful substance that has a biological origin. The effect of a toxic substance can be > immediate (acute toxicity) > prolonged (chronic toxicity)

Compounds that can counter- act the effects of a poison by destroying it or rendering it ineffective are called antidotes. eg. chelates for metals, thiosulfate('hypo') for cyanide

The lethal dose of a substance is the quantity that causes death The lethal dose of a substance is the quantity that causes death. The LD50 of a chemical is the amount that kills exactly half of a large population of animals. as: mg(of substance) / Kg(of body weight) ie. Smaller = worse; Larger = better Problems: children have much lower LD50 values possible synergisms of mixtures can't extrapolate between species directly "Dosis sola facit venenum" - the dose makes the poison. (Paracelsus, 1493-1541)

Toxicity Classes Class supertoxic extremely very moderately slightly Water!! LD50(mg/kg) < 5 5 – 50 50 – 500 500 – 5000 5000 –15000 > 15g For 70kg male < 7 drops 7 dps – 1 tspn 1 tspn – 1 oz 1 oz – 1 lb 1 lb – 4 lb > 4 lb

LD50's for Several Chemicals LD50 (mg/kg, orally to rat) Chemical (*=natural) *Ethanol *Sodium chloride Aspirin *Caffeine *Heroin *Lead *Cocaine *Sodium cyanide *Nicotine *Strychnine 10000 3750 1750 200 150 20 17.5 10 2 0.8

LD50s of some of the Most Lethal Poisons LD50 (mg/kg, orally to rat) Substance (*=natural) *Botulinum toxin *Tetanus toxin *Diphtheria toxin 'Dioxin'(TCDD) *Muscarine(mushrooms) Sarin(nerve gas) *Tubocurarine(arrow poison) Parathion(insecticide) *Aflatoxin(peanut mold) *Solanine(greenspots on potatoes) 3 x 10-8 5 x 10-6 3 x 10-4 3 x 10-2 2 x 10-1 4 x 10-1 7 x 10-1 4 10 42

LD50 Values for Dioxin Species LD50 (mg/kg) Guinea pig Rat Monkey Rabbit Dog Mouse Hamster Bullfrog Human?(few deaths) 0.0006 0.04 0.07 0.12 0.15 0.20 3.5 >1.0 ~40kg/400km2 in Seveso, Italy,1976; Vietnam(agent orange)

Toxicity of Dioxin vs Botox Botulinum toxin is 1 million times more toxic than Dioxin! But we still use Botox for cosmetic purposes!! Human vanity trumps safety concerns!!

Botox treatments Botox injections are a diluted form of botulinum toxin (botulism) which are injected into facial (or other) muscles to paralyze or weaken the muscles that form wrinkles (nerve impulses are blocked) 1.6 million done in USA in 2006 Results last 3-4 months and require occasional touchups

Botox treatment cont’d Approved for use by US FDA in 2002

Warnings! Patient must remain upright and avoid alcohol for several hours after injection Botulinum injections are also under study for possible treatment of migraines and juvenile cerebral palsy *** The Dose is everything!!

US FDA Issues Botox Warning! Feb 9, 2008 re: Botox, Botox Cosmetic and Myobloc products Severe adverse reactions (including deaths) May be related to overdosing Toxin may spread from injection site Symptoms: difficulty swallowing, talking breathing, general weakness

Most severe effects In children with cerebral palsy, being treated for spasticity in limbs (not an FDA approved treatment) No use permitted for ages<12.

Toxic doses can enter an organism by three means inhalation ingestion skin contact Huge differences in LD50, eg. nicotine: orally(230mg) vs. intravenously(0.3mg) anthrax: inhalation vs. skin contact

Premature Death - What will Kill You? In NA an est. 1 million/yr die prematurely Chemical: in your food? - not too likely second-hand tobacco smoke ~3500 Sociological(ie. lifestyle): heart disease(obesity & smoking) ~500,000; cancer(>60% diet & smoking) ~200,000 Physical: murder ~22,000; car accidents? war? Biological: food poisoning ~10,000(~7 million ill) Geological: ? Radiation?? Worldwide: TB(3 million), measles(1.2 million), malaria(2 million), drinking contaminated water (3 million children under 5)

The Death of Socrates (Jacques Louis David – 1787) Socrates – a cup of Hemlock ‘Tea’ The Death of Socrates (Jacques Louis David – 1787)

Safety = the degree of acceptability of risk at either the individual or societal level. Eg. warning labels on products screw-cap bottle tops for aspirin nitrites/nitrates(carcinogens) in processed meats vs. botulinum smoking(individual 'rights' vs. public health safety & cost) tetrodotoxin(puffer fish) in Japan ( ~100 deaths/yr!)

The acceptable daily intake (ADI) of a food additive is 1% of the maximum daily amount of ' additive' that produces no observable effect* on laboratory animals (at least two and usually more). Any long-term hazards must also be considered. *no effect level = mg/kg of body wt for that animal (NB. much less than the LD50)

corrosive metabolic neurotoxic mutagenic teratogenic carcinogenic Toxic substances can be classified according to the way in which they disrupt body chemistry as: corrosive metabolic neurotoxic mutagenic teratogenic carcinogenic

Corrosive poisons destroy tissue which, if critically situated, can render the person(animal?) incapable of functioning. Corrosive poisons are usually: strong acids strong bases/alkalis oxidizing agents

Some Corrosive Poisons Strong acids: sulfuric acid(auto batteries) hydrochloric/muriatic acid(tile/concrete cleaner) Strong bases: sodium hydroxide(drain/oven cleaners-aerosols!) ammonia(window cleaners) Oxidizers: ozone(photocopiers/smog) hypochlorite/peroxide(bleach) chloramine/nitrosyl chloride gases(from mixing household ammonia + bleach!)

Metabolic Poisons A metabolic poison causes illness or death by interfering with a vital bio- chemical mechanism to such an extent that it ceases to function or is prevented from functioning efficiently. Two principal 'mechanisms of action' : > affect oxygen transport or oxidative processes in the cell > 'disable' certain proteins by reacting with -SH groups

Will it Kill me or just make me High? Does it contain ? 1) amatinin – a cyclic peptide(metabolic poison) from the amanita phalloides mushroom. 2) psylocibin – a seretonin analog(hallucinogen) from Teonancatal(psylocibe mexicana), the magic/ sacred mushroom.

The human body can usually accommodate small, repeated doses of many metabolic poisons because detoxification mechanisms (in liver) exist for them. However, over a long period of exposure, the build up of subacute doses of these cumulative poisons (which the body cannot efficiently eliminate) can lead to chronic effects. These usually result in a lessening of the efficiency of body functions, such as motor skills or cognitive ability. If these functional impairments are not recognized, damage becomes cumulative, with serious disabling or even lethal effects. Those having no warning properties are especially dangerous.

Jimson Weed seeds : a cheap and very dangerous high Also known as fireweed, devil’s apple, stinkweed, Jamestown weed, angel’s trumpet, magical strawberries, thorn apple 15 Cornwall teenagers hospitalized (Oct /07) Attacks CNS, causes fever, racing heart, blurred vision, hallucinations Seizures, coma and at least 2 deaths in Canada

Beautiful (but dangerous!)

Carbon Monoxide*- binds with Heme(Iron) Oxyhemoglobin (aq) + CO (g) Carboxyhemoglobin (aq) + O2(g)g If a person breathes air with a CO conc'n. higher than about 0.1%, formation of carboxyhemoglobin is favoured (60% conversion after 4hrs - and death!). When a victim is exposed to fresh air (pure O2) the equilibrium favours oxyhemoglobin. * from incomplete combustion, eg. kerosene heaters/BBQs/generators indoors, auto exhaust, cigarettes, smoldering leaves. ~250 million tons/yr generated in NA

Individuals differ in their tolerance of carbon monoxide, but generally those with anemia or other- wise low reserves of hemoglobin, eg. children are more susceptible to its effects. A pregnant woman who smokes can damage her fetus because carbon monoxide from the inhaled tobacco smoke can deprive the fetus of the oxygen it needs during critical developmental stages. Studies consistently show that low birth weight is closely related to the mother’s smoking habits.

Cyanide (HCN / NaCN) Irreversibly complexes to iron(Fe3+) of cytochrome oxidases (glucose oxidizing enzymes). Used to fumigate cargo ships/warehouses for insects & rodents. 50mg = death in seconds. Hydrogen cyanide(bp26o) Amygdalin Ar-HC(CN)-O-Sugars + 2H2O HCN + 2C6H12O6 + Ar-CHO Glucose Benzaldehyde Amygdalin(seeds of cherry/plum/peach/apple/apricot) = laetrile(contoversial anti-cancer 'drug')

Other Metabolic Poisons - Heavy Metals - Bind to various proteins, via -SH groups; thus changes structure(denaturation)  changes function. Kidney/liver damage, neurological effects, cancer >>>>>>>

Some Metal Poisons Arsenic - favourite homicidal poison, eg. Arsenic and Old Lace (Agatha Christie); present in - pressure treated wood (Cu/Cr/As), some insecticides, shrimp (~15ppm). Mercury - 'Mad Hatter's disease'(Alice in Wonderland); present in - thermometers, tooth amalgams, fluorescent lights, fungicides, mining & extraction (Minimata disease). Also: nickel, cadmium, chromium, copper/iron/zinc!

Lead - Environmentally Ubiquitous Lead often occurs in beverages (20-30 g/L), foods (100-300 g/kg), public water supplies (100g/L, from old lead- sealed pipes) and even air. Until the phase-out of lead in automobile fuels in the '80s, lead in air came primarily from automobile emissions. Today because so much lead was deposited from auto exhausts over the years, lead is still found in soil samples and even on city sidewalks and streets. Until the '80s most paints contained lead-based pigments. Even continuous handling of bullets, lead foil or toy soldiers can cause problems.

One of the major sources of lead is drinking water that has contacted lead-containing pipes, joints and plumbing fixtures. In 1993 the US EPA released a list of public water supplies that exceeded its maximum allowable level of 15 ppb lead. Hundreds of cities and towns were on the EPA list, some were as high as 484 ppb! We hope Canada isn't as bad.

On continuous exposure, lead can accumulate in the body, principally in the bones. The average person can excrete about 2 mg (2000 g)/day of lead; fortunately one’s daily intake is normally less than this. If intake exceeds this amount, accumulation and storage result. . In bones lead acts on the bone marrow (skeletal problems). . In soft tissues lead behaves like other heavy-metal poisons(metabolic problems). . Lead can also affect the central nervous system (neurological problems).

For adults in the workplace where lead exposure would be expected, the acceptable blood lead level is 40 g/dL. US estimates are ~500,000 miscarriages per year due to lead 'poisoning'.

Children are much more susceptible to lead poisoning: • for under six years of age 10 g/dL is the acceptable blood level. They do not 'store' lead in their bones. •many children (especially from low-income homes) chew old paint, play in city streets and are undernourished. In the US an estimated 1 in 6 are above this intervention level, ie. >10,000/yr with some mental retardation due to excess lead levels.

Effects of Lead(g/dL) in Children's Blood Blood levels Acute effects Chronic Effects ~5 none blood pressure ~10 none intelligence 15-20 none heme/vit D synthesis 25-40 none IQ, impaired CNS/ hearing/hemoglobin 40-80 CNS damage anemia >80 convulsions, mental retardation coma, death?

Lead in Montreal Water supply March 2007 Homes in Plateau Mont Royal,Villeray and Notre Dame de Grace districts still serviced by lead pipes! 400,000 households Children under 6 and pregnant women should only drink filtered water

Lead in Ontario School Drinking water: the law is an Ass! November 2007; 5 minute flushing of pipes in all schools-no money for staff to do this .Waste of water. Solution test for lead-easy to do. Restrictions to bottled water only in affected schools

A type of metabolic poison limited to action on the nervous system. Neurotoxins A type of metabolic poison limited to action on the nervous system. These include botulinum toxin, strychnine, curare, atropine ('natural' alkaloids) and 'organophosphates' (nerve gases & insecticides).

A nerve impulse is transmitted along a nerve fiber by an electrical impulse carried by the movement of ions. Between one nerve fiber and the next is a gap called a synapse. The impulse / 'message' is carried across this gap by acetylcholine (a neurotransmitter) which then binds to a receptor on the adjacent nerve. The acetylcholine is then removed/recycled (by acetylcholinesterase) so the system can continue to function properly.

The CNS and a Nerve Synapse axon synapse

Acetylcholine – the Ubiquitous Neurotransmitter The human brain operates at ~25 W and can handle ~10 trillion bits of info’. The Central Nervous System (CNS) has 12 billion (109) neurons containing 1013(>10 trillion) synapses. Of more than 100 different neurotransmitters perhaps the most prevalent is acetylcholine: O CH3C-OCH2CH2-N+(CH3)3 For proper functioning the acetylcholine from I ‘synaptic firing’ must be ‘cleared’ within 2 milliseconds.

Neurotoxins affect the transmission of the nerve impulses by interfering with this neurotransmitter function in three ways. Block the synthesis of acetylcholine: no messenger = no impulses = paralysis(botulinum) Block the receptor site: no impulse received = rapid heart beat = death(atropine- also dilate pupils; curare - also muscle relaxant; local anesthetics) Inhibit the 'removal': neurotransmitter builds up = nerves 'fire' wildly = convulsions or death (organophosphates as nerve gases or insecticides)

Nerve Gases (LD50,mg/kg) Insecticides Sarin(0.55) Parathion(10) Tabun(3.7) Malathion(1000) Soman(0.8)

Teratogens Chemical agents that can cause birth defects are called teratogens. From the Greek 'terat' meaning 'monster'. In addition to chemicals, high-energy radiation and some viral agents are known teratogens. Birth defects occur in 2% to 3% of all births. About 25% of these occur from genetic causes, 5% to 10% are the result of known teratogens and the remaining ~60 % result from unknown causes..

In the development of the newborn, there are three periods during which the fetus is at risk. 1) For ~17 days between conception and implantation of the fertilized egg in the uterine wall, a chemical “insult” will result in cell death. If a 'lethal dose' is administered, death of the organism occurs, followed by spontaneous abortion or reabsorption. The so-called 'morning-after' pill, RU-486, (developed in France in 1988 ) works in this way.

The morning after pill A modified steroid

2) In the period 18 to 55 days after fertilization is the critical embryonic stage during which organogenesis (organ development) occurs. At this time the embryo is extremely sensitive to teratogens. Contact with teratogens results in reduction of cell size and number; this is manifested in growth retardation and failure of vital organs to reach maturity. 3) During the fetal period (from 56 days to term), the fetus is less than sensitive to chemical insults.

Any chemical substance that can cross the placenta is a potential teratogen. During pregnancy any 'toxic' chemicals in the mother’s blood( esp. days 18-55) might prove dangerous for the well-being of the fetus. Smoking results in higher levels of: carbon monoxide, hydrogen cyanide, cadmium, nicotine, and benzo- pyrene( a PAH). Fetal alcohol syndrome(mental retardation) and cocaine addiction are observed in many newborns delivered by mothers who consume ethanol or use cocaine.

Teratogens Effects on the fetus can be: eye defects, abortion, brain/neurological damage, limb/skeletal defects, growth retardation. Some known organic human teratogens are: thalidomide('60s), accutane(acne medication), ethanol(FAS), PCBs, diethylstilbestrol (synthetic growth hormone). Others from animal studies: caffeine. Some inorganics(animal studies only): arsenic, cadmium, cobalt, gallium, lead, mercury, thallium, zinc. Often are waste by-products of industrial processes.

Mutagens Agents (chemicals, irradiation, etc.) capable of altering the genes and chromosomes sufficiently to cause abnormalities in offspring. Mutagens alter the structures of DNA and RNA, that transmit the traits of parent to offspring. Although many chemicals are under suspicion because of their mutagenic effects on laboratory animals. As yet there is no conclusive evidence that any chemical causes mutations in human germinal cells( slowness of life cycle, probabilities, etc.)

Mutagens Some examples from plant/animal studies: LSD, aflatoxin (moldy peanuts), maleic hydrazide (plant growth inhibitor), mustard gas, ozone, captan (a fungicide), toluene/ethyl acetate (solvents in glue), caffeine, benzopyrene (from cigarette and coal smoke), chloroprene (monomer for plastics), *nitrites/nitrous acid (preservatives) *Sodium nitrate continues in use as a preservative in processed meats because it is the most effective agent for preventing the growth of the deadly micro- organism botulinum. Many countries are decreasing allowable limits.

Carcinogens Carcinogens cause the growth of tumors. The mechanisms are not clearly understood. A tumor is an abnormal growth of new tissue; they can be either benign or malignant.

Benign tumors are slow growing and do not invade neighbouring tissue; they often regress. Malignant tumors( cancers?) can grow slowly or rapidly but irreversibly. They invade and destroy neighbouring tissue and often lose specialized functions. The term 'cancer' is applied to about 200 different afflictions and may take 10-20 years to manifest itself.

Some Human Carcinogens NB. Many of these examples are 'industrial chemicals' that present a particular danger for exposed workers. Inorganic: arsenic(insecticides, alloys, treated wood), asbestos(brake linings, insulation?), cadmium/chromium/nickel(metal plating) Organic: benzene/carbon tetrachloride/ethylene oxide(industrial solvents), acrylonitrile/vinyl chloride(plastics monomers), benzopyrene (tobacco smoke), nitrosamines(frying bacon)

Industries and their Hazardous Waste Products Industry plastics pesticides medicines paints petroleum metals leather textiles Associated Waste organochlorines organochlorines, organophosphates organic solvent residues, heavy metals heavy metals, pigments, solvent residues oil, phenols, metals, strong acids/bases fluorides, cyanides, plating salts, phenols metals, solvent residues metals, dyes, solvents

Carcinogens - How do we Know? Bacterial screening: in the '80s(at U Cal) Prof. Bruce Ames developed a simple test that can identify chemicals that cause mutations in sensitive strains of bacteria. The Ames test can identify not only mutagenic chemicals, but potential carcinogens (~90% correlation). Animal testing: usually with ~30 animals (+controls ) and high/toxic(?) doses. Each test = ~$1 million & 2 yrs. Realistic doses? Different metabolisms! Are there low but safe thresholds? Epidemiological studies: statistical analyses of human populations with higher than normal illness rates to pinpoint common factors. Not 'legal' !

Cancer Deaths - Perception vs. Reality

Natural Carcinogens There are ~30 identified human carcinogens plus ~300 for animals. Very few are synthetic chemicals. Many plants contain molds / fungi or produce chemicals, as protective insecticides(?), that are not only toxic but carcinogenic as well. These become part of our food supply. >>>>>>>>>>>

It is estimated that 99. 99% of ingested carcinogens are 'natural'; eg It is estimated that 99.99% of ingested carcinogens are 'natural'; eg. in basil, 'bruised' celery / fennel, mustard / horseradish, pepper, citrus oils, saffrole / oil of sassafras(banned as flavouring for 'root beer'!) Remember antioxidants probably are anticarcinogens. Eat your cruciferous veggies(cabbage, broccoli, kale brussel sprouts,) as 'natural' sources of vit. A, C, E.

Arithmetic example for LD50s: 1) Cocktail shrimp(5g) may contain 15ppm arsenic. How many must be eaten by a 70kg person to reach the 15mg/kg level?

# shrimp required! 15mg/kg for a 70 kg person= 70x.015g=1.05g Each shrimp contains 5 x15 ppm of arsenic =5x15x10-6g or .000075g # shrimp required =1.05/.000075= 14,000!

Radiation Dangers E=hv (h=Planck’s) v=frequency c (Speed of light)=wavelength x v Thus v =c/wavelength So E=h x c/wavelength Thus longer wavelength = lower E!

Electromagnetic spectrum

Most dangerous radiation X-rays (high E) Gamma rays: destroy cells UV : can cause skin cancer Longer wavelengths generally safer (radio, microwaves),but……………..

Can cell phone use cause cancer? Frequencies are in microwave region Some evidence that living close to a communications tower may endanger health in long term (yrs): headaches,sleep disruptions, altered memory function Vodafone towers in London UK: (175, 000 in USA)

Some extreme views! “Dr”. Mercola says “using cell phones is far more dangerous than smoking cigarettes ever was!” Your views???????????

On balance Extensive use of hand held cell phones by children should be avoided Use speaker phones where possible Should be no problem with moderate use

Other radiation dangers Living close to high voltage power lines High magnetic fields Lots of anecdotal evidence re: cancer induction Childhood leukemia risk elevated

Some risk……………. 1979 study: children living within 40 meters of high voltage line were~ 2-3 x more prone to leukemia 1996 National Academy of Science Study : no conclusive evidence of adverse effects

Leachates from plastics Phthalates and Bisphenol A in the news! Concerns re: microwave /heat effects on plastics, degradation etc.

Why is Bisphenol A used? Production of polycarbonate based plastics Used in epoxy linings in canned foods and drinks (extends shelf life) “to protect canned foods from contamination by corroded metal and bacteria” (polycarbonate/BPA group of the American Chemistry council)

Structure of BPA 2 phenol rings

Polycarbonates from Bisphenol A Use phosgene (Cl)2C=O Reacts with OH group to form carbonates and HCl

Infant safety? Commonly used “sippy cups” and baby bottles are made of polycarbonate plastics with BPA’s present

The findings 95% of US adults (2006) had traces of BPA in urine (ppb level) Rat study suggests increased breast cancer risk BPA’s act as “estrogen” mimics “could be a factor in the increased incidence of breast cancer over the last 50 years”

Estrogen Mimics (endocrine Disrupters) BPA causes mammary gland hyperplasia (an abnormal increase in the number of cells): similar to estrogen General effects: more estrogen mimics in the environment may also be responsible for decreasing levels of testosterone in serum among US males (~ 1% reduction per year)

Endocrine Systems Glands and hormones that regulate development, growth, reproduction and behavior of all species Include thyroid, pituitary and adrenal glands in humans

Less is more! Small doses (ng) of BPA’s affect the endocrine system more than large ones Body’s hormone receptor sites ignore big doses, because hormones don’t arrive in big doses If a small signal is seen “that’s a hormone signal”

Conflicting results (2007) 2 US gov’t convened panels reached nearly opposite conclusions re: Safety of BPA’s Routes of ingestion may be important BPA free plastics now available Avoid microwave, dishwashers Glass, porcelain or stainless steel alternatives

Phthalates in plastics Used as plasticizers Also function as estrogen mimics Also in some baby lotions, shampoos and powders May influence long term reproductive capacity (ie. lower testosterone) in males

Plasticizers are everywhere Additives that increase the fluidity or “plasticity” of the material to which they are added Added to concrete, wallboard and plastics! Phthalates used where good resistance to water and oils is required

That new car smell Plasticizers work by embedding themselves between chains of polymers such as PVC, thus increasing the “free volume” of the polymer and making it softer and more flexible Some evaporation occurs: in enclosed space giving the characteristic odour

Structures of phthalates Plasticizers

Flame retardants (PBDE’s) 2 ppm levels found in some fish Polybromodiphenyl ethers: used to prevent upholstery, electronics, carpets from catching fire Structurally similar to the hormone thyroxine

Other endocrine disruptors? PBDE’s

Thyroxine structure Also a halogenated diphenyl ether

The future: endocrine disruptors Not lethal : no LD50 data. Effects are much more long term and subtle Feminization of the human race?? (maybe good for world peace!)

Estrogen Structure A steroid

Are there any specific criteria? Estrogen mimics do not have to be structurally similar to estrogen. But, the aromatic (benzene ring) is common to all

Other Estrogen mimics Many pesticide residues: metabolites from chemicals used vs. mosquitoes/locusts/rats/ants/agricultural pests etc

Pesticide residues Insecticides such as DDT (1st made in Germany in 1874) (dichlorodiphenyltrichloroethane) used extensively after WWII Paul Muller (Nobel Prize in medicine for showing its use as a potent insecticide in 1948)

BUT…………….. Rachel Carson studied its harmful effects “Silent Spring” 1962 DDT resisted degradation, highly fat soluble, harmful effects on birds (weakened egg shells) ,fish ,mammals Highly restricted for use in NA in 1973 But still used in Africa to combat malaria

DDT: a chlorinated insecticide Still made in USA for export

DDT: a strong estrogen mimic Note presence of benzene ring! Reproductive habits of fish strongly influenced by DDT

DDT use is controversial!! W.H.O. says more DDT should be used in Africa to combat malaria Environmental groups say NO “DDT vs. Death by Malaria” Alternatives: Rick Mercer/Belinda Stronach “malaria net” program $10 pp.

Other Toxins of Note: Ricin LD50 value= 1.6 x10-3. (~ 105 less toxic than botulinum) A protein extracted from the castor bean Consists of 2 distinct chains (Ricin A and Ricin B) linked by disulfide (S-S) unit Can be denatured by heating; only active if Ricin B stays bonded (allows entry into cells)

Uses as a military agent Bulgarian dissident Georgi Markov assassinated by Bulgarian police with a pellet containing Ricin (1978) Death took several days after shooting Dangerous mainly since it is easy to make and no known antidote (but can be denatured readily by heating). Much less dangerous than botulism or anthrax.