Toxic Materials CommunicationAnondho Wijanarko, ChESP-UI

Toxic MaterialsMaterials which, upon entering an human body is capable of producing disease or death

Toxicity factor consist of (1) The quantity of the material (2) The rate and extent to which the material is absorbed into the bloodstream via intravenous, inhalation, intraperitoneal, intramuscular, subcutaneous, oral or cutaneous (3) The rate and extent to which the material is biologically transformed in the body to breakdown product.US Department of Transportation Regulation

Toxic MaterialsHEAVY METAL POISONS (Arsenic, Lead, Mercury salts) DISEASE AGENT (BIOHAZARD) Botulinum Toxin, Ricin toxin, Epsilon toxin, Staphlococcus enterotoxin B, Shigella toxin (Shigella dysenteriae toxin or Stx , CAS # 75757-64-1), Shigella-like toxins produced by Escherencia coli O 157(Shiga-like toxin 1, verotoxin 1, or Stx-1, and Shiga-like toxin 2, verotoxin 2 or Stx-2 )TOXIC GASES Asphyxiant (CO, HCN, NO), Irritant (NO2, H2S, SO2) Anesthetic (diethyl eter, N2O2) ORGANIC PESTICIDES INSECTICIDE Aldrin, DDT, Parathion, Chlordane, Diazinon, Dieldrine, Lindane, Malathion, Methoxychlor, CarbylUS Department of Transportation Regulation

TOXIC CHEMICALSAll substances are intrinsically toxic (hazard) whether or not the inherent toxicity will become a risk depends on the Dose received and the Recipients sensitivity to the chemical concentrationThe Dose received and the Recipients sensitivity can be combined in a dose/response curves to examine the response of a population to different levels of a toxin

TOXIC CHEMICALS

CHEMICALSThe dose/response curve shows that some exposure is necessary before most individuals respond. Hence, toxic effects of chemicals are concentration dependent

CHEMICALS: Major Types of ToxicityAcute toxicity: It involves lethal concentrations and short-term exposures Acute effects of a toxin appear immediately after exposure.The end point is usually death, hence it is used to derive LD50An LD50 is a dose of a toxic chemical that kills half of the population.LD50 is obtained by plotting, for a given dose the proportion of the population that responded to that dose and all lower doses

CHEMICALS: Major Types of Toxicity

CHEMICALS: Major Types of ToxicityChronic toxicity: It involves Sub-lethal concentration and long-term exposureChronic toxicity test is used to derive Effective Dose (ED50): Is the dose by which half of the population has been affectedEffect could be anything but deathED50 is obtained by plotting, for a given dose the proportion of the population that responded to that dose and all lower dosesChronic effects of a toxic response can last a long time or be permanent.

CHEMICALS: Major Types of ToxicityThe end points of chronic toxicity could be: biochemical physiological These ends points may lead to responses at organism level (e.g. behavioral and production changes) Responses at organism level could lead to effects on population which could have implications at the community level Responses at community level could also be implicated at ecosystem level.

CHEMICALS: Major Types of ToxicityUnder chronic conditions the organism survives but production or gene frequency could be affected.This is the level (sublethal) of interest in ecotoxicology.Typical example is the effect of DDT on egg shell thinning in birds. Here the birds survived DDT exposure but their reproduction mechanisms was affectedUnlike transient pollution which has a passing effect on gene frequency, chronic pollution changes the environment.

Intentional Poisoning*

AdvantagesGenderSilent Male46%Precise targeting Female39%Depersonalized Unknown16%Safe for attacker

ProfileBackgroundCaucasianPublic71%MalePhysician 8%Average or above intelligencePolitical 4%UnderachieverNurse 4%Personality defectOther 5%Cowardly, nonconfrontationalUnknown 9%NonathleticNeat and orderly, meticulousCareful planner*Source: Criminal Poisoning (2000)LonerJ. H. Trestrail, Humana Press

Properties of Ideal Poison

Undetectable by sensesSolubleDelayed effectEasily obtainedNot traceableSymptoms mimic actual diseaseChemically stable (?)Undetectable by instrumentationPotent

The dose makes the poison

Potencies of Poisons

AgentLethal dose

Botulinum toxin 0.05 mg

Ricin 0.5 mg

Strychnine 100 mg

Sodium arsenite 200 mg

Sodium cyanide 250 mg

Thallium1000 mg

NB: A dime is 2300 mg

Sources of Poisons

Commercial

Laboratories

Underground catalogs

Antique drug collections

Hobbies/natural sources (e.g., plants)

Pesticide Poisons of Note

Synthetic OrganophosphatesCarbamates Paraquat Fluroacetate (1080 bait)

Plant-derived Oleander Poison hemlock Mushroom Ricin Atropine/belladonna Nicotine Strychnine Cyanogenic glycosides

Top 5 Homicidal Poisons

Agent FrequencyTarget

Arsenic 31%Energy generation

Cyanide 9%

Strychnine 6%Nervous system

Morphine 3%

Chloroform 2%

Toxin Background Analysis

Evidence in vicinity of victimPill bottle, drug paraphernaliaFood, beverage leftoversSymptomsAcuteChronicSamplingOrgans, fluidsAccessory materialDetectionAnalytical instrumentationHPLC, GC, Mass SpecMotivationLove, money, powerDisguised as random

Poison Symptoms

Constricted/dilated pupils (opioids, organophosphates)

Breath odor (arsenic garlic)

Hair loss (thallium)

Convulsions (strychnine)

Paralysis (botulism)

Coma (depressants, hypnotics)

Skin color (CO cherry red; nitrites blue)

Skin appearance (arsenic hyperkeratosis, warts) (dioxin chloracne)

ArsenicCan be used as pesticideAffects skin, liver, nervous systemIs a risk factor for lung cancerHistory and physical examUrine test (can be affected by seafood consumption)

Arsenic As at. No 33 m.p. 613oAbundance & Userelatively rare, no nutritional roleuses include pesticides, pigments, wood preservatives, marine paintfound in WI H20, added to chicken feedPharmacologytoxicity: As+3 > As+5 > organic (shellfish)salts > oxidesefficiently absorbed from gutexcreted in urine, does not accumulatebinds to SH groups

Effectsarsine gas = hemolysis/renal failureG.I. = bloody vomiting & diarrhearenal & vascular necroses--gangrenealopecia, mees lines, bronzing, garlic odor

Assessmenturine, hair semi-reliablemeasured by AA, ICP, colorimetrytreated with dimercaprol (BAL), DMSA

Arsenic Trioxide1 to 2.5 mg/kg - potentially fatal dose binds to cellular proteins containing sulfhydryl groupsdecrease in glutathione necessary for the metabolic detoxification of arsenicCommon toxidrome:Abdominal pain, nausea/vomiting,malaiseNeuropathiesPancytopeniasHepatitisPeripheral vascular diseaseCardiovascular collapse

Arsenic Trioxide>500 years use in traditional Chinese medicine1970s investigators in China reported its use in APL but were ignored by mainstream medicineDual apoptotic and differentiation inducing propertiesDoses 0.06-0.2 mg/kg (~1/3 fatal dose)CR rates ~90% in de-novo APL

And if you change your mind?the earlier the betterChelation therapy Dimercaprol (BAL)DMSOContraindicationspre-existing renal disease, pregnancy, concurrent use of iron, G6PD

Cadmium Cd at. No 48 m.p. 321oAbundance & Usefound w/Zn in 1:70 rationo nutritional roleused in electroplating, batteries, solder, plasticsPharmacologybiological 1/2 life >10 yearstoxicity inhaled > ingestedstrong emeticinternal metallothionen chelationsubstitutes for Zn in enzymes

Effectsemphysemanephrotoxicity, increased Ca excretionosteomalacia, itai-itai disease, kidney stones

Assessmentblood, urine, urinary proteinsmeasured by AA, ICPZn administration confers protectionchelation may increase bioavailability

DioxinsDioxinsWhat are they?Dioxin is a general term for hundreds of chemicals formed by burning chlorine based compounds with hydrocarbons (www.ejnet.org/dioxin, 2002)What do they do?They get into the air, then soil and water, and then our food chainThey attach and accumulate in our fat cellsDioxin is passed onto our childrenThrough placenta, and breastfeedingWe have no defense because it is not metabolized in our bodiesIt can cause serious health problems at parts per trillion (www.acereport.org,2003)

(www.ejnet.org/dioxin,2002)

Harmful Effects of DioxinCauses cancerDisrupts hormonesMay shrink penis size and sperm countMiscarriage, reproductive disorders, birth defects, low birth weightLearning disabilitiesShort term memory and attention spanDamage to nervous and immune systems (www.acereport.org,2003)

TCDD (dioxin) Chloracne

Poisoning of Victor Yushchenko just before Ukraine presidential election

Dioxin (TCDD) Sensitivities

SpeciesLD50 (g/kg)

Guinea pig 2Rat 40Monkey 50Human ?Mouse 130 Rabbit 200Hamster4000

Autopsy samples

Organs (brain, liver, kidney, muscle)Blood (heart, peripheral)Vitreous humor Bile (insoluble metabolites)Urine (soluble)Gastric contents (alkaloids)

HairBoneMaggots

Environmental/Accidental Contamination

Differential diagnosisAccidental death or homicide?Compensable injury or carelessness?Background that could confound interpretation

Verify authenticity/natural source or show adulterationHow did the mass poisoning occur?Substitution of inferior/contaminated component?

Track source of environmental contaminationEnvironmental justice for underserved?Safeguards not enforcedChildren often victimsWhich companies are breaking the law?

Marine Toxins in Food

PufferfishDelicacy in Japanese restaurantsGives tingling of lips when properly preparedTetrodotoxin concentrated in liver and ovary (removed)Blocks sodium channel in nervesFatal in excess (lethal dose 1 mg)

Shellfish Tainted by Red Tide (3 examples)Saxitoxin Paralytic shellfish poison (blocks sodium channel), potentially fatalDomoic acid Amnesic shellfish poison (glutamate neurotransmitter analog)Disorientation, loss of short term memory at moderate dosesFatal excitotoxin activity at higher dosesOkadaic acid Diarrhetic shellfish poison (phosphatase inhibitor), nonfatal

Harmful Algal BloomsThought increasing due to coastal pollution, ocean warmingOf 4,400 known algal species, >1% produce toxinsKnown causes of wildlife epidemicsMarine mammal mortality off California coast from domoic acid

Accidental Food Contamination

Iraq 1972: 5-6,000 people hospitalized, 10% died.Seed grain donated with methyl mercury antifungal agent.Distributed 100,000 tons to farmers, improperly identified.Grain (wheat, barley) mistakenly used to make bread.

Michigan 1973: Nearly 2 million livestock destroyed.Several hundred pounds PBBs mixed with dairy feed.Coverup by company and state officials compounded problem.

Spain 1981: 11,000 people hospitalized, >500 died.Industrial rapeseed oil from France containing aniline refined.Refining process produced toxic components.Resold fraudulently as cooking oil (59 tons) after mixing olive oil.

Adulturation of vegetable oils (soybean/canola in olive) frequent.Biochemical components becoming available for detection.

MercuryUsed as pesticide, pigment or preservativeCan cause central nervous system, behavioral and renal effectsHistory, physical examUrine testing

Mercury Hg at. No 80 m.p. -39oCharacteristics & Useliquid at RT, high vapor pressureGood electrical conductorAll forms toxicmany usesdental amalgamsseed, paint, wood preservative (mostly banned)lamps, switches, thermometersindustrial catalystmedicines (mostly historical)

Hg Chemistry & PharmacologyChemical form importantall toxic, but:effects and pharmacology differinfluences best samples for assessmentMetallic mercury Hgoinhaled vapor ~80% absorbedingestion is nontoxicexcreted in urine (& respired air)urine best test sample

Hg Chem & Pharm, contInorganic mercury (Hg salts) Hg++G.I. absorption 2-38%excreted in bile and urinetest urine or bloodOrganic mercury Ch3Hg+nearly 100% G.I. absorbedpossible dermal absorptionexcreted in bile, some reabsorbedtest blood or hair

Sources of HgNatural sources = 33-50% of totalvolcanoes weathering of mercury-containing rocksAnthropogenic sources = 50-67% of totalmining and smeltingcinnibar ore, HgScombustion of coal 80% anthrowaste incinerationOther municipal/industrial releases

Hg Exposure PathwaysHg vapor precipitates, enters waterwaysSediment bacteria methylateMethylmercury biomagnifies in fish

Dietary intake biggest exposure source

Commercial Activity - Mercury A woman holds a victim of "Minamata Disease", or mercury poisoning, in Minamata, Japan, in 1973. The girl has a malformed hand, like many victims of the disease who suffer from physical deformities and mental retardation. Chisso Corporation, a Japanese fertilizer, petrochemical and plastics company, dumped an estimated 27 tons of mercury compounds into Minamata Bay between 1932 and 1968. Up to10,000 people were affected byeating seafood from the bay.Many sources of mercury exist, either natural (fish) or associated with human activity (chloralkali plants, gold mines, effluent from power plants).Elemental form is methylated by micro-organisms in the environment.

Hg Exposure Pathways, contHg vapor from household products

Hg Health EffectsMetallic Hgprimarily affects CNS, kidneys, & lungstremor, personality changes, deleriumfatigue, anorexia, excess salivationacrodynia, pink diseaseeffects often reversible

Inorganic HgG.I. tract necrosiscramps, bloody diarrhea, circulatory collapserenal failuretooth & jaw necrosis, black gum linesno major CNS effects

Hg Health Effects, contEffects Ch3Hg+potent neurotoxinparasthesias, esp. lips and fingersataxia, slurred speech, blurred visionconfusion & agitationpenetrates skin and latex

Commercial Activity - Lead

Targets: Blood cells (anemia), kidney (gout), sperm (infertility) Nervous system most sensitive target

Adults: Occupational exposures Lead smelters, battery factories, lead additives Painters got peripheral neuropathy (wrist drop)

Children: Colic (acute) and mental retardation (chronic) Legacy of leaded paint and gasoline Eating peeling paint (many inner cities) Playing in contaminated yards (e.g., Oakland)

Commercial activity Acrylamide

Sweden 1997: Hallandsas tunnel construction halted.Acrylamide used in grouting to prevent water seepage.20 workers experienced neurological symptoms (reversible).Several cows grazing nearby showed severe neural effects.Dead fish found in hatchery supplied by water from tunnel.Acrylamide found in ground water near tunnel.

Sensitive methods developed to detect acrylamide showed high background levels in humans.

Surprisingly high levels found in fried foods (potato chips).

Potential exposures in typical labs using acrylamide gels(including DNA identification labs).

AsbestosUsed in plaster, fire retardants, taxidermyCan can pulmonary fibrosisCan result in lung cancerOSHA Asbestos Standard:Annual exam and termination examHistory, physicalPulmonary function studyPeriodic chest x-ray

SolventsUsed to clean and thin paintsCan affect skin, liver, blood (benzene), peripheral and central nervous systemsHistory and physical examUrine for metabolitesCarbon monoxide in exhaled air, or carboxyhemoglobin in blood for methylene chloride

Intracellular Targets of Neurotoxins

Ion channels Signal conductionSodiumPotassiumCalciumChloride

Synaptic region Neurotransmitter processingReleaseReuptake of excessReceptor response (stimulate, block)

Channels and receptors - multigene familiesLocated in different parts of the nervous systemResponsible for differential effects

Psychoactive/Psychedelic

MarijuanaShort term use relaxation; Long term loss of motivationLoss of coordination, slow reaction time, disordered thoughtLegalized for medical use in some states (controversial)Sometimes contaminated with herbicide paraquat

LSDStrong hallucinogen, vivid colorsFlashbacks common

PCP/KetamineAt first, feelings of strength, invulnerability, detachmentThen confusion, agitation, depressionLong term depression, suicide, schizophrenia

Natural sourcesCacti (peyote) mescalineMushrooms psilocybin, ibotenic acid

Depressants

AlcoholResponsible for about half of traffic deathsPoor job performance and disrupted family lifeHealth problems: Cirrhosis, Fetal alcohol syndrome

Barbiturates (sedatives)Sleep inducing, can induce dependenceEspecially dangerous when used with alcohol

Tranquilizers (anxiolytics)Benzodiazepines (Valium, Librium) among most usedVariants not approved include RohypnolCauses loss of short term memoryUsed for personal attacks

Drugs of AbuseOpioids, Amphetamines, Cocaine

Scope of problem in USAHalf a million heroin addictsSix million cocaine usersPersonal tragedies common among usersFamilies adversely affected (vicious circle of poverty, crime)75% of crime lab evidence is drug relatedImpurities always suspect

FeaturesStimulation of reward center: Euphoria (like endorphins)Increase dopamine in nucleus accumbensTolerance: Require increasing doses (100x, previously fatal)Continued use can lead to psychoses (paranoid schizophrenia)Withdrawal: Dysphoria, depression, craving

Opioid Action as Analgesic

Codeine not attractive as street drug (low potency)

Maintenance: Methadone prevents withdrawal, no euphoriaSaid to obviate need for marijuana as painkiller

Research to find derivatives with only analgesic action

Only partially successful: Oxycontin used by 1 millionpatients with chronic pain, 25% abuse use

Illicit syntheses often attempted, often consequences tragic.

Poor technique dangerous derivatives (Parkinsons)

Cocaine derivatives in clinical use

Lidocaine, procaine successful as local anesthetics

Result from blocking neuronal sodium channels

Uses of Amphetamines and Derivatives

Treatment for narcolepsy - 1930s

Maintaining military alertness - 1940s

Occupational alertness (students, truckers) 1950s

Appetite suppressant

Suppress childhood attention deficit disorder

Dietary supplement (ephedrine) as natural energizer

Toxic MaterialsPROTECTION : (1) Recirculating oxygen (2) Demand compressed air/O2 (3) Recirculating self generating oxygen (4) Suits wear that made of material impervious to the toxic materialUS Department of Transportation Regulation

Oxygen content (suffocation)O2 Requirement

% O2 in airSigns and Symptoms19.5 23.5Recommended level for safe operation15 19Decreased ability to work strenuously, May impair coordination, early symptoms in persons with circulatory problems12 17Loss of balance, dizziness. Respiration deeper, increased pulse rate, impaired coordination, perception and judgment.10 12Heavy breathing and high pulse rate, performance failure, giddiness, poor judgment, lips blue, possibly brain damage8 10Mental failure, nausea, vomiting, unconsciousness, ashen face, blueness of lips. 8 minutes: 100% fatal, 6 minutes: 50% fatal, 4 5 mins: recovery with treatment, brain damage possible4Coma in 40 secs, convulsions, respiration ceases, death.

CHEMICAL THREATSChemical warfare agents (CWAs) Mustard (HD)Nerve agents (G, V)Have seen previous terrorist use (Aum Shinrikyo)Toxic industrial chemicals (TICs) Large array of materialsReasonably accessibleAccidents have caused numerous casualties (Bhopal)Non-traditional agents (NTAs)Not TICs