Toxic Materials Communication

Anondho Wijanarko, ChESP-UI

US Department of Transportation Regulation

Toxic Materials
Materials 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.

Transportation Regulation

Toxic Materials

HEAVY

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 # 7575764-1), 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 (NO , H S, SO )
2
2
2
Anesthetic (diethyl eter, N O )
2 2

ORGANIC PESTICIDES

TOXIC CHEMICALS
All

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 concentration
The 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

CHEMICALS
The

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

Toxicity
Acute 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 LD50
An 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 Toxicity

Chronic

toxicity: It involves Sub-lethal

concentration and long-term exposure
Chronic toxicity test is used to derive
Effective Dose (ED50): Is the dose by which
half of the population has been affected
Effect could be anything but death
ED50 is obtained by plotting, for a given dose
the proportion of the population that
responded to that dose and all lower doses
Chronic effects of a toxic response can last a
long time or be permanent.

CHEMICALS: Major Types of Toxicity

The

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 Toxicity

Under 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 affected
Unlike transient pollution which has a passing effect
on gene frequency, chronic pollution changes the
environment.

Intentional Poisoning*
Advantages

Gender

Silent
Precise targeting
Depersonalized
Safe for attacker

Male
Female
Unknown

Profile

Background

Caucasian
Male
Average or above intelligence
Underachiever
Personality defect
Cowardly, nonconfrontational
Nonathletic
Neat and orderly, meticulous
Careful planner
Loner

Public
Physician
Political
Nurse
Other
Unknown

46%
39%
16%

71%
8%
4%
4%
5%
9%

*Source: Criminal Poisoning (2000)

J. H. Trestrail, Humana Press

Properties of Ideal Poison

Undetectable by senses
Soluble
Delayed effect
Easily obtained
Not traceable
Symptoms mimic actual disease
Chemically stable (?)
Undetectable by instrumentation
Potent

The dose makes the poison

Potencies of Poisons
Agent

Lethal dose

Botulinum toxin

0.05 mg

Ricin

0.5 mg

Strychnine

100 mg

Sodium arsenite

200 mg

Sodium cyanide

250 mg

Thallium

1000 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

Organophosphates
Carbamates
Paraquat
Fluroacetate (1080 bait)

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

Poison plants readily available from

nurseries, arboreta, backyards, wild areas

Foxglove
purpurea

Datura

digitalis

atropine

Not visible: Lupine (lupanine)

Oleander Autumn Poison Lantana

crocus hemlock
cardiac colchicine coniine
glycosides

Ricinus communis
(Castor bean)

lantadene

ricin

Top 5 Homicidal Poisons

Agent

Frequency

Target

Arsenic

31%

Cyanide

9%

Strychnine

6%

Morphine

3%

Chloroform

2%

Energy generation

Nervous system

Toxin Background Analysis

Evidence in vicinity of victim
Pill bottle, drug paraphernalia
Food, beverage leftovers
Symptoms
Acute
Chronic
Sampling
Organs, fluids
Accessory material
Detection
Analytical instrumentation
HPLC, GC, Mass Spec
Motivation
Love, money, power
Disguised 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)

Arsenic
Can

be used as pesticide
Affects skin, liver, nervous system
Is a risk factor for lung cancer
History and physical exam
Urine test (can be affected by seafood
consumption)

Arsenic As
Abundance

at. No 33 m.p. 613o

& Use

relatively rare, no nutritional role

uses include pesticides, pigments,

wood

preservatives, marine paint

found in WI H 0, added to chicken feed
2
Pharmacology
toxicity:

As+3 > As+5 > organic (shellfish)

salts > oxides

efficiently

absorbed from gut

excreted in urine, does not accumulate
binds to SH groups

 Effects
arsine

gas = hemolysis/renal failure

G.I. = bloody vomiting & diarrhea
renal & vascular necroses--gangrene
alopecia, mees lines, bronzing, garlic odor
Assessment
urine,

hair semi-reliable
measured by AA, ICP, colorimetry
treated with dimercaprol (BAL), DMSA

Arsenic Trioxide

1 to 2.5 mg/kg - potentially fatal dose

binds to cellular proteins containing sulfhydryl groups
decrease in glutathione

necessary for the metabolic detoxification of arsenic

Common toxidrome:

Abdominal pain, nausea/vomiting,malaise

Neuropathies
Pancytopenias
Hepatitis
Peripheral vascular disease
Cardiovascular collapse

Arsenic Trioxide
>500 years use in traditional Chinese medicine
1970s investigators in China reported its use in
APL but were ignored by mainstream medicine
Dual apoptotic and differentiation inducing
properties
Doses 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
better
Chelation therapy

Dimercaprol (BAL)
DMSO

Contraindications

pre-existing renal
disease, pregnancy,
concurrent use of iron,
G6PD

Cadmium Cd
Abundance

at. No 48 m.p. 321o

& Use

found

w/Zn in 1:70 ratio

no nutritional role
used in electroplating, batteries, solder,
plastics
Pharmacology
biological

1/2 life >10 years

toxicity inhaled > ingested
strong emetic
internal metallothionen chelation

substitutes

for Zn in enzymes

 Effects
emphysema
nephrotoxicity,

increased Ca excretion
osteomalacia, itai-itai disease, kidney
stones
Assessment
blood,

urine, urinary proteins

measured by AA, ICP
Zn administration confers protection
chelation may increase bioavailability

Dioxins

Dioxins
What 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 chain
They attach and accumulate in our fat cells
Dioxin is passed onto our children
Through placenta, and breastfeeding
We have no defense because it is not metabolized in
our bodies
It can cause serious health problems at parts per
trillion
(www.acereport.org,2003)

(www.ejnet.org/dioxin,2002)

Harmful Effects of Dioxin

Causes cancer
Disrupts hormones
May shrink penis size and sperm count
Miscarriage, reproductive disorders,
birth defects, low birth weight
Learning disabilities
Short term memory and attention span
Damage to nervous and immune
systems
(www.acereport.org,2003)

TCDD (dioxin) Chloracne

Poisoning of Victor Yushchenko just before Ukraine presidential election

Dioxin (TCDD) Sensitivities

Species

LD50 (g/kg)

Guinea pig
Rat
Monkey
Human
Mouse
Rabbit
Hamster

2
40
50
?
130
200
4000

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

Environmental/Accidental Contamination
Differential diagnosis
Accidental death or homicide?
Compensable injury or carelessness?
Background that could confound interpretation
Verify authenticity/natural source or show adulteration
How did the mass poisoning occur?
Substitution of inferior/contaminated component?
Track source of environmental contamination
Environmental justice for underserved?
Safeguards not enforced
Children often victims
Which companies are breaking the law?

Marine Toxins in Food

Pufferfish
Delicacy in Japanese restaurants
Gives tingling of lips when properly prepared
Tetrodotoxin concentrated in liver and ovary (removed)
Blocks sodium channel in nerves
Fatal in excess (lethal dose 1 mg)

Shellfish Tainted by Red Tide (3 examples)

Saxitoxin Paralytic shellfish poison (blocks sodium channel), potentially fatal
Domoic acid Amnesic shellfish poison (glutamate neurotransmitter analog)
Disorientation, loss of short term memory at moderate doses
Fatal excitotoxin activity at higher doses
Okadaic acid Diarrhetic shellfish poison (phosphatase inhibitor), nonfatal

Harmful Algal Blooms

Thought increasing due to coastal pollution, ocean warming
Of 4,400 known algal species, >1% produce toxins
Known causes of wildlife epidemics
Marine 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.

Mercury
Used

as pesticide, pigment or preservative

Can cause central nervous system,
behavioral and renal effects
History, physical exam
Urine testing

Mercury Hg

at. No 80 m.p. -39o

Characteristics

& Use
liquid at RT, high vapor pressure
Good electrical conductor
All forms toxic
many uses
dental amalgams
seed, paint, wood preservative (mostly banned)
lamps, switches, thermometers
industrial catalyst
medicines (mostly historical)

Hg Chemistry & Pharmacology

Chemical

form important

all

toxic, but:
effects and pharmacology differ
influences best samples for assessment
Metallic

mercury Hgo

inhaled

vapor ~80% absorbed

ingestion is nontoxic
excreted in urine (& respired air)
urine best test sample

Hg Chem & Pharm, cont

Inorganic

mercury (Hg salts) Hg ++

G.I.

absorption 2-38%
excreted in bile and urine
test urine or blood
Organic
nearly

mercury Ch3Hg+

100% G.I. absorbed

possible dermal absorption
excreted in bile, some reabsorbed
test blood or hair

Sources of Hg
Natural

sources = 33-50% of total

volcanoes
weathering

of mercury-containing rocks

Anthropogenic
mining

sources = 50-67% of total

and smelting

cinnibar ore, HgS

combustion

of coal
80% anthro
waste incineration
Other municipal/industrial releases

Hg Exposure Pathways
Hg

vapor precipitates, enters waterways

Sediment bacteria methylate
Methylmercury 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 to
10,000 people were affected by
eating 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, cont

Hg

vapor from household products

Hg Health Effects
Metallic

Hg

primarily affects CNS, kidneys, & lungs

tremor, personality changes, delerium
fatigue, anorexia, excess salivation
acrodynia, pink disease
effects often reversible

Inorganic Hg
G.I. tract necrosis
cramps, bloody diarrhea, circulatory
collapse

renal failure
tooth & jaw necrosis, black gum
lines
no major CNS effects

Hg Health Effects, cont

Effects Ch3Hg+
potent

neurotoxin
parasthesias, esp. lips and fingers
ataxia, slurred speech, blurred vision
confusion & agitation
penetrates 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).

Asbestos
Used

in plaster, fire retardants, taxidermy

Can can pulmonary fibrosis
Can result in lung cancer
OSHA Asbestos Standard:
Annual

exam and termination exam

History, physical
Pulmonary function study
Periodic chest x-ray

Solvents
Used

to clean and thin paints

Can affect skin, liver, blood (benzene),
peripheral and central nervous systems
History and physical exam
Urine for metabolites
Carbon monoxide in exhaled air, or
carboxyhemoglobin in blood for methylene
chloride

Intracellular Targets of Neurotoxins

Ion channels Signal conduction
Sodium
Potassium
Calcium
Chloride

Synaptic region Neurotransmitter processing

Release
Reuptake of excess
Receptor response (stimulate, block)

Channels and receptors - multigene families

Located in different parts of the nervous system
Responsible for differential effects

Psychoactive/Psychedelic
Marijuana
Short term use relaxation; Long term loss of motivation
Loss of coordination, slow reaction time, disordered thought
Legalized for medical use in some states (controversial)
Sometimes contaminated with herbicide paraquat

LSD
Strong hallucinogen, vivid colors
Flashbacks common

PCP/Ketamine
At first, feelings of strength, invulnerability, detachment
Then confusion, agitation, depression
Long term depression, suicide, schizophrenia

Natural sources
Cacti (peyote) mescaline
Mushrooms psilocybin, ibotenic acid

Depressants
Alcohol
Responsible for about half of traffic deaths
Poor job performance and disrupted family life
Health problems: Cirrhosis, Fetal alcohol syndrome

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

Tranquilizers (anxiolytics)
Benzodiazepines (Valium, Librium) among most used
Variants not approved include Rohypnol
Causes loss of short term memory
Used for personal attacks

Drugs of Abuse
Opioids, Amphetamines, Cocaine
Scope of problem in USA
Half a million heroin addicts
Six million cocaine users
Personal tragedies common among users
Families adversely affected (vicious circle of poverty, crime)
75% of crime lab evidence is drug related
Impurities always suspect

Features
Stimulation of reward center: Euphoria (like endorphins)
Increase dopamine in nucleus accumbens
Tolerance: 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 euphoria
Said to obviate need for marijuana as painkiller
Research to find derivatives with only analgesic action
Only partially successful: Oxycontin used by 1 million
patients 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

US Department of Transportation Regulation

Toxic Materials
PROTECTION :
(1) Recirculating oxygen
(2) Demand compressed air/O2
(3) Recirculating self generating oxygen
(4) Suits wear that made of material
impervious to the toxic material

O 2 Requirement

Oxygen content (suffocation)

% O2 in air
19.5 23.5

Signs and Symptoms

Recommended level for safe operation

15 19

Decreased ability to work strenuously, May impair coordination, early

symptoms in persons with circulatory problems

12 17

Loss of balance, dizziness. Respiration deeper, increased pulse rate,

impaired coordination, perception and judgment.

10 12

Heavy breathing and high pulse rate, performance failure, giddiness,

poor judgment, lips blue, possibly brain damage

8 10

Mental 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 possible

Coma in 40 secs, convulsions, respiration ceases, death.

CHEMICAL THREATS

warfare agents (CWAs)

Mustard (HD)
Nerve agents (G, V)
Have seen previous terrorist use
(Aum Shinrikyo)

Chemical

Toxic industrial chemicals (TICs)

Large array of materials
Reasonably accessible
Accidents have caused numerous casualties (Bhopal)

Non-traditional agents (NTAs)

Not TICs