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 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 counteract 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 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
LD50(mg/kg)
For 70kg male
supertoxic
extremely
very
moderately
slightly
Water!!
<5
5 – 50
50 – 500
500 – 5000
5000 –15000
> 15g
< 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
Chemical
(*=natural)
*Ethanol
*Sodium chloride
Aspirin
*Caffeine
*Heroin
*Lead
*Cocaine
*Sodium cyanide
*Nicotine
*Strychnine
LD50
(mg/kg, orally to rat)
10000
3750
1750
200
150
20
17.5
10
2
0.8
LD50s of some of the Most Lethal Poisons
Substance
(*=natural)
LD50
(mg/kg, orally to rat)
*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
0.0006
Rat
0.04
Monkey
0.07
Rabbit
0.12
Dog
0.15
Mouse
0.20
Hamster
3.5
Bullfrog
>1.0
Human?(few deaths)
~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)
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)
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 biochemical 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 otherwise 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
2C6H12O6
Glucose
+
HCN +
Ar-CHO
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 leadcontaining 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
~10
none
none
blood pressure
intelligence
15-20
none
heme/vit D synthesis
25-40
none
IQ, impaired CNS/
hearing/hemoglobin
40-80
CNS damage
>80
convulsions,
coma, death?
anemia
mental retardation
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
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
O
O P F
Sarin(0.55)
S
O P O
NO2
O
O
Parathion(10)
N P CN
O
S
Tabun(3.7)
O
O P F
CH3
Soman(0.8)
CH3O P S
COOC2H5
OCH3
COOC2H5
Malathion(1000)
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 benzopyrene( 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 microorganism 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. 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.