Chemicals are Evil

1. 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.

2. Dangerous Chemical Causes asphyxiation when inhaled into lungs, killing thousands of people each year, often young children. In gaseous state, will cause deadly burns. Maims and kills thousands each year this way, often young children. Major component of tumor cells. In the environment, this chemical causes more destruction of human lives, property, and wildlife than all other chemicals combined.

3. 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.

4. Why does everyone fear chemicals and believe “natural” means safe?

5. 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: 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) Cancer Test: Multiple animals are fed MTD of molecule for a period of time and the animals are examined for tumors

6. 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.

7. 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

8. 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

9. Why does everyone fear chemicals and believe “natural” means safe? Is it because synthetic chemicals cause more cancer?

10. 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

11. Where are we? Half of all chemicals tested cause cancer in the rodent test whether synthetic or natural. Are we in danger? 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).

12. 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.

13. 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. Where are we? Half of all chemicals tested cause cancer in the rodent test whether synthetic or natural. Are we in danger? Ames, et al., Mutation Research, 2000, 447, 3-13

14. Case History: Benzopyrene from meat on a barbecue Natural molecules can become dangerous during food preparation!

15. 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!

16. 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.

17. 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

18. 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

19. 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

20. 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

21. Although they are valuable test subjects, rodents are not humans and there are even numerous differences between different rodent studies

22. 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.

23. Are modern drugs less effective and/or more dangerous than natural herbal remedies?

24. 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.

25. 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

26. 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.

27. 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

28. 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

29. 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

30. 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

31. 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

32. 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.