Download For synthetic chemicals tested in both mice and rats

Chemicals are Evil
A closer look at the science behind the
widely held belief that “natural” is safe and
“synthetic” causes cancer
Brent Iverson, UT Chemistry Dept.
Dangerous Chemical
1. Causes asphyxiation when inhaled into lungs, killing
thousands of people each year, often young children.
2. In gaseous state, will cause deadly burns. Maims and kills
thousands each year this way, often young children.
3. Major component of tumor cells.
4. In the environment, this chemical causes more destruction
of human lives, property, and wildlife than all other
chemicals combined.
Take home lessons
Most of the world believes that natural means safe and
synthetic causes cancer, even though they are apparently both
equally dangerous based on animal tests.
It has been very profitable ($10 + $4 billion) to sell natural
alternatives in industries such as organic foods and herbal
remedies.
So far,when tested, the science largely does not support these
alternatives on the basis of safety concerns alone.
Better testing procedures are needed to provide more realistic
risk assessments.
Why does everyone fear
chemicals and believe “natural”
means safe?
Why does everyone fear chemicals and believe “natural” means safe?
Is it because synthetic chemicals cause more cancer?
First, we need to explain how chemicals are tested for
cancer:
1. Toxicity Test: Rodents (mice, rats, guinea pigs) are fed
increasing doses of a chemical to find maximum dose
that is tolerated by the animal without causing death
from poisoning - called “maximum tolerated dose”
(MTD)
2. Cancer Test: Multiple animals are fed MTD of molecule
for a period of time and the animals are examined for
tumors
Why does everyone fear chemicals and believe “natural” means safe?
Is it because synthetic chemicals cause more cancer?
3. Dosage Test: Chemicals that cause tumors at MTD
might be diluted to find concentration at which half the
animals get tumors. This identifies very potent
compounds.
4. Establishment of Exposure Risk: Different approaches
here, but most common is to take the MTD or the
concentration determined in 3. and divide by 1,000,000
to give a guideline for human exposure.
Why does everyone fear chemicals and believe “natural” means safe?
Is it because synthetic chemicals cause more cancer?
For synthetic chemicals tested in both mice and rats:
271/451 cause cancer tumors
60%
Ames, et al., Mutation Research, 2000, 447, 3-13
Why does everyone fear chemicals and believe “natural” means safe?
Is it because synthetic chemicals cause more cancer?
For synthetic chemicals tested in both mice and rats:
271/451 cause cancer tumors
60%
For natural chemicals tested in both mice and rats:
79/139 cause cancer tumors
57%
Ames, et al., Mutation Research, 2000, 447, 3-13
Why does everyone fear chemicals and believe “natural” means safe?
Is it because synthetic chemicals cause more cancer?
Why does everyone fear chemicals and believe “natural” means safe?
Is it because synthetic chemicals cause more cancer?
Ames, et al., Mutation Research, 2000, 447, 3-13
Where are we?
Half of all chemicals tested cause cancer in the rodent test
whether synthetic or natural. Are we in danger?
1. Probably not. Very few molecules cause cancer at the low
levels we are exposed to normally.*
*The exceptions are a few notorious cases of worker exposure such
as ethylenedibromide, benzopyrene, carbon tetrachloride, etc.
2. Cancer rates are NOT rising* and basic cancer rates are
correlated with age. CANCER IS PROBABLY A NORMAL
CONSEQUENCE OF AGING, JUST LIKE ALL THE
OTHER KNOWN PROBLEMS SUCH AS GRAY HAIR,
VISION LOSS, DROOPING FEATURES, ETC.
*The exceptions are lung cancer and skin cancer rates, which are
increasing due to behavior (smoking and sunburns).
Where are we?
Half of all chemicals tested cause cancer in the rodent test
whether synthetic or natural. Are we in danger?
Surprising conclusion: Within error, all cancers can be
accounted for through a combination of behavior
(smoking, sunbathing to excess, eating habits) and natural
aging. So far, there is no statistical validity to the
assertion that our contaminated environment is causing
cancer in humans.
Surprising conclusion: It is important to clean up
contaminating chemicals in the environment to avoid
wildlife toxicity, but human cancer rates are unlikely to
change in a significant way even in a pristine environment.
Where are we?
Half of all chemicals tested cause cancer in the rodent test
whether synthetic or natural. Are we in danger?
Calibration: Even heavy coffee drinkers do not drink enough of
these chemicals to pose a real threat and NO cancer link has
been found with coffee.
Ames, et al., Mutation Research, 2000, 447, 3-13
Case History: Benzopyrene from meat on a barbecue
Natural molecules can
become dangerous
during food preparation!
Does our diet put us in danger?
Half of all chemicals tested cause cancer in the rodent test
whether synthetic or natural. Are we in danger?
Surprising conclusion: A correlation between diet and cancer
has been found: a lack of certain vitamins (especially folic
acid) in unhealthy diets (among the poor) leads to 4-fold
increase in cancer! This is likely due to the crippling of
natural cancer fighting mechanisms.
Surprising conclusion: There is always orders of magnitude
more “food” molecules in food then pesticide residue.
Because they are consumed in much larger amounts, the
natural chemicals pose a far greater risk of causing cancer
than the very small amount of pesticide residue on even
unwashed produce!
Scaled for
exposure levels
and relative
potency in the
rodent test,
pesticides from
unwashed food
are orders of
magnitude less
dangerous in a
normal healthy
diet compared
to the natural
chemicals in
the food.
Billions of dollars are spent on significantly more costly organic
foods - often in an effort by consumers to avoid pesticide
residue-but to date the science does not support this.
It is unlikely the increased consumption of organic foods will
reduce cancer rates
Organic Trade Association 2004 Market Overview
Billions of dollars are spent on significantly more costly
organic foods - often in an effort by consumers to avoid
pesticide residue-but to date science does not support this
Salmonella and other dangerous bacteria including E. coli
0157:H7 are present around farm animals, and
contaminate meat products. They are eliminated through
proper cooking temperatures.
Organic produce is generally fertilized using farm animal
manure. Since produce is not cooked, this can be a
significant source of bacterial food poisoning. A recent
study found 22.4% of organically grown lettuce
contaminated with E. coli. Wash your lettuce!
Mukherjee, et al., J. Food Prot., 2004, 67, 894-900
Case History: Dioxin
Dioxin is common byproduct
of insecticide production.
One of the most potent tumor
forming chemicals ever tested
in Guinea pigs! Operates
though strong interaction with
estrogen receptors in guinea
pigs.
Despite dramatic publicity to the contrary,
scientific studies failed to find link exposure to
human cancer although it is a toxin. Human
estrogen receptors are different from those in
guinea pigs!
Victor Yuschenko of
the Ukraine
Where are we?
Half of all chemicals tested cause cancer in the rodent test
whether synthetic or natural. Are we in danger?
Surprising conclusion: It is widely believed that the rodent
test can identify dangerous compounds, but it also can
overestimate danger because:
•
Rodents have different biochemistry compared to humans.
•
The MTD used causes toxicity, leading to cell
stress/death, triggering rapid cell division that makes
cancer more likely. i.e. many observed rodent tumors are
a result of toxicity, not cancer causing potential
Although they are valuable test subjects, rodents are not
humans and there are even numerous differences between
different rodent studies
Good news!
The FDA has just announced new guidelines for assessing
risk.
The new guidelines focus on standardized procedures and
more critical analyses using the latest science to better
distinguish false positives from truly dangerous
compounds.
It is still not clear how to estimate any possible effects of
low levels of exposure or to rationally set realistic
exposure limits.
Are modern drugs less
effective and/or more
dangerous than natural
herbal remedies?
Herbal Remedies vs. Drugs
Herbal remedies represent a $4 billion industry.
History: Drug companies have long used folk remedies
derived from plants as a starting point for identifying new
drugs. Active ingredients are identified, purified, studied
and sold as drugs. Examples include aspirin (from willow
bark) and digoxin (from the foxglove plant)
The advantage of single active chemicals as drugs is that
they can be manufactured and studied as reproducibly
pure materials. Herbal remedies cannot be studied or
manufactured with the same level of reproducibility if the
important ingredients have not been identified.
Herbal Remedies vs. Drugs
The FDA drug approval process 10 years and $800 Million.
All metabolites of a
drug must also be
tested now.
All drug
manufacturing
must follow very
strict General
Manufacturing
Practices (GMP)
protocols.
http://www.fda.gov/cder/handbook/develop.htm
Case History: Seldane and Allegra
Seldane heralded as first
non-drowsy antihistamine.
Demonstrated to be safe
through FDA testing.
Patients started dying from
heart troubles!?!
Investigation revealed 1) Seldane rapidly converted by enzyme (cyt P450) in
body to Allegra. 2) Allegra is actually the effective and safe antihistamine.
3) Seldane is actually cardiotoxic. Some patients were taking other
medications (antibiotics, anti-fungals) that inhibit cyt P450, causing Seldane
to persist and cause toxicity. Allegra now approved and highly prescribed.
All drug metabolites must now tested.
Herbal Remedies vs. Drugs
The FDA herbal remedy approval process. There is none.
Manufacturer makes claim of safety and efficacy.
Manufacturing entirely uncontrolled.
The FDA only investigates when consumers report problems
Case History: Echinacea
An extract of flowers from the Echinacea genus is thought
to boost immune systems and help relieve symptoms of the
common cold.
Sold by large number of different companies and has been
a very successful product from a profit point of view.
Two recent large, FDA style double blind studies failed to
find any efficacy for treatment compared to placebo.
In a recent survey, of 46 brands of echinacea purchased in
the Denver area, only 50% had the level of extract promised
on the label, and six contained no echinacea at all!
2005, Harvard Health Letter, 6-7
Case History: St. John’s Wort
An extract of Hypericum perforatum
(aka St. John’s Wort) thought to relieve
symptoms of depression with no side
effects. Sold by large number of different companies with
sales as high as $86 Million in the US. In Europe,
especially Germany, it is prescribed by M.D’s substantially
more than drugs like prozac.
Multiple attempts have failed to identify any specific active
components.
Small early studies indicated efficacy for mild depression.
More recent FDA-style larger double blind studies showed
no real effect greater than placebo with more severe
depression.
Linde, et al., 2005, British Journal of Psychiatry, 186, 99-107
Related Trend: Herbal Remedies vs. Drugs
The FDA herbal remedy approval process. There is none.
Manufacturer makes claim of safety and efficacy.
Manufacturing entirely uncontrolled.
The FDA only investigates when consumers report problems
The NIH has started funding comprehensive FDA style
studies on herbal remedies, but the results have disappointed
many
Bottom line
Better testing procedures are needed to provide more realistic
risk assessments at realistic, low levels of exposure.
Until such tests are widely performed and the results
publicized, the world will probably stay convinced that:
Chemicals are Evil
Take home lessons
Most of the world believes that natural means safe and
synthetic causes cancer, even though they are apparently both
equally dangerous based on current animal tests.
It has been very profitable ($10 + $4 billion) to sell natural
alternatives in industries such as organic foods and herbal
remedies.
So far, when tested, the science largely does not support these
alternatives on the basis of safety concerns alone.
Better testing procedures are needed to provide more realistic
risk assessments.