The Safe-Dose Myth

The Science.

"There is simply no safe dose of mutagen. 
This is a central tenet in the fields of molecular toxicology and cancer epidemiology."

–  Dr. Wallace LeStourgeon, PhD, Professor of Biological Sciences, Vanderbilt University.

       Dr. LeStourgeon made these statements to the Metropolitan Board of Public Health in Nashville because of his professional concern about and opposition to using ULV spraying of mosquitoes to try to control West Nile virus.  In a letter to the Board, Dr.  LeStourgeon, who teaches an advanced course in environmental toxins at Vanderbilt, makes these additional sobering statements:

1.  95-98% of all cancers are caused by mutations in somatic cells as we pass through life and not by the inheritance of defective parental genes.

2.  Today 46%, essentially half of all white males, and 39.5% of all white females will be diagnosed with cancer in their lifetime.  [Note – the rate is only slightly less for African Americans.]

3.  Mutations are cumulative throughout our lifetimes . . . This is why cancer is referred to as a disease of the elderly . . . [this] is a misconception . . . cancer incidence and onset correlates most directly with the "rate" and "magnitude" of DNA damage and is not strictly correlated to age. 

4.  Tissues that show the maximum rate of increased cancer in recent years are precisely the same tissues that are most in harm's way from the mutagens in the environment.

    For the non-specialists among us, Dr. LeStourgeon explains: "mutagens are chemicals that directly or indirectly induce DNA damage (a mutation).  All mutagens are carcinogens (chemicals that induce cancer-causing mutations).  DNA is a chemical, and the only way to modify a chemical is with another chemical.  While irradiation (X-ray, UV light, etc.) is a powerful mutagen, at the molecular level, the DNA damage induced by irradiation is actually chemical." 

    Relative to our local situation in Sacramento and Yolo counties there is abundant evidence that the PBO/pyrethrum mix sprayed by SYMVCD from airplanes over populated areas and Suspend SC, sprayed from backpacks and containing the pyrethroid Deltamethrin, are mutagens (below see the scientific references that accompanied Dr. LeStourgeon's letter in Nashville).

    Dr. LeStourgeon's point 3 above deserves special emphasis.  In less technical language, this molecular biologist says that there is nothing inherent about the aging process itself that causes cancer or sets the stage for cancer in our bodies; rather, the culprit is the exposure to mutagens and accumulation of mutations throughout our lives.  A lifetime exposure to low doses is serious due to the fact that once a mutation occurs in a cell, the progeny of that cell will carry the damage.  So, we accumulate mutations as we pass through life -– the concentration and DNA damage increase, the elderly have had more time to accumulate the mutations, and the probabilities of getting various cancers thus increase over time.  Against this backdrop do we really wish to spray populated areas with what the Sacramento County Public Health Officer has called "very potent chemicals" (see below)?

    As to the full contents of the letter, Professor LeStourgeon states "I believe that if the general public knew this information, they would choose not to expose themselves or their children to a risk that likely exceeds that from mosquito-borne illness."

    He explains his position in more detail in "Evidence that a Safe Dose of Mutagen Does Not Exist."  He also notes that, except for lung cancer and several other easily diagnosed precancerous conditions, the cancer rate is increasing, the exposure is cumulative, and "even the best DNA repair system in the most healthy person can not detect and repair all premutational lesions prior to DNA replication."  The scientific message, spelled out in more detail below, seems clear that we must begin to decrease our exposure to environmental toxins instead of spraying populated areas with them, particularly since these particular ones are so completely ineffective at slowing the transmission of WNv to humans.

Fact: It is against federal law for pesticide applicators to claim that a pesticide is “safe.” The pesticide used in our area, Evergreen 60-6 consists of 6% pyrethrin, 60% piperonyl butoxide, and 34% unknown. PBO is listed by the EPA as a Group C carcinogen. The remaining 34% are only listed as “other ingredients.” However, “other” or “inert” ingredients are not inert in the usual sense of the word; often they are neither chemically, biologically, nor toxicologically inert (NCAP).

See references to other papers about dose at the end of this page.

The Local Spray Politics.

    In contrast to the clear and well-supported scientific message from Dr. LeStourgeon, the political message from local vector control and public health officials in this district is, essentially, that the dose is so low that it can't hurt you.  Or, alternatively, the risk from WNv is much greater than the risk of exposure to the spray.  As examples, here are a few excerpts from officials' testimony before the Sacramento City Council on August 9, 2007.  A DVD of the session can be obtained from the City Council office.  Time zero on the DVD was the beginning of the evening session, a few minutes after 6:00, and council members asked about safety of the sprayed chemicals and supporting studies at several points:

17:18:  Dr. Glennah Trochet, Sacramento County Public Health Officer: " . . . the risk assessment is that the risk of the ultra-low volume pesticide that is sprayed for 3 to 6 days a year, or every 2 years as it happens in Sacramento, is so low compared to risk of somebody having a life-changing event such as having paralytic disease from West Nile virus that it is very well worth that risk."

19:26:  Trochet:  "There are some ongoing studies. Most of them are looking at very high levels of pesticides.  The amounts of pesticide that people are exposed to through this spraying are so low that to my knowledge there are no ongoing studies.  It is almost not worth the money."

21:30:  David Brown, District Manager of SYMVCD:  " . . . at our very low doses there is minimal risk of the pesticides . . . "

31:40:  Brown:  " . . . at the low dosages there is minimal risk . . . "

32:38:  Trochet:  "Exposures to those pesticides at those levels so far have not shown large amounts of cancer in anyone other than the people who actually are exposed to the pesticides, either in production or in the handling of them at high doses."

33:03:  Trochet:  "We may find in the future that there are problems."

33:24:  "Unfortunately, it is impossible to have absolute certitude about every public health intervention we have.  . . .   But I am sorry but I cannot give you with absolute certitude that someone 30 years from now won't have cancer.  What I can tell you with great certitude is that if we continue to have high numbers of infected mosquitoes we will continue to have death, people who are paralyzed for life and people who have neuroinvasive disease.  That I can tell you for sure." [Emphasis ours.]

37:53:  Trochet:  "There is no question that these are very potent chemicals, but the poison is in the dose."  [Emphasis ours.]

42:57  Trochet:  "The preponderance of the evidence is that it does not have major health effects.  Again, like fluoride, like any chemical, the higher dose you take, the higher the risk of having adverse consequences.  But at the dosage used there is no evidence that it has health consequences."  [Emphasis ours.]

    First, officials have shown no scientific evidence or rigorous modeling to indicate that spraying 3 days a year with insufficient kill rates has any chance to make any difference whatsoever in the transmission of WNv to humans, given a mosquito population that grows exponentially during the better part of the season.  Some mosquitoes are killed, to be sure, but that is not the point.  The question is whether enough mosquitoes are killed to slow the transmission of WNv to humans, they have no solid scientific evidence of this, and there is solid scientific evidence to the contrary (e.g. Pimentel, 2004;Reddy, et al., 2006)

    Second, Trochet seems to say that exposing hundreds of thousands of citizens in this district to "very potent chemicals" is justified if it can prevent even one person from having a life-changing event through WNv, which is simply not a proportional public health concern.  According to county and state information, there had been at most four neuroinvasive WNv cases in Sacramento this year and none in Yolo County, as of 8/18/08.  As to relative risk, in the vast majority of infections WNv produces no symptoms, in about 20% of the cases it produces very mild flu-like symptoms, and in about 0.67% of the cases it produces a more severe disease that may become fatal.  While any fatality is tragic, note that an average of approximately 17 possible WNv deaths a year over the last four years in all of California reveals an extremely low relative risk, as this pales in comparison to the over 7000 deaths a year from flu and pneumonia in the state, for example. 

    Third, we do not have and have not had "high numbers of infected mosquitoes."  Officials declare an "epidemic" if they find 5 infected mosquitoes per 1000 captured, but we have asked for and received no justification for this figure they use in their "risk assessment" – no models or studies.  It seems to have been borrowed from what has been done with St. Louis Encephalitis, it does not come from any forecasting model that has been revealed to us, but vector control presents it as one.  Both its predictive validity and its significance for WNv are very questionable, as is their entire risk-assessment method.

    It is also important to note that a new study has just been published, which indicates that "Patients infected with West Nile virus can develop long-term symptoms such as fatigue, fuzzy thinking and movement difficulties but these symptoms go away after about a year," according to a Reuters article.

    Fourth, Dr. Trochet seems uninformed about the current research about the safety of what is being sprayed.  She explicitly notes that she is unaware of any "low-dose" studies.  Contrast that with what Dr. LeStourgeon has supplied (see the full detail below).

    Fifth, the message could not be more clear that these officials want us to believe that the danger is only in high doses of these "very potent chemicals" – the poison is in the dose, so they say – but the caveat that we may find problems in the future and the contradictory statements about low risk (17:18 and 33:24) and no evidence of health consequences (42:57) of the spray suggest that they really do not know what they are doing, at least in part because of their lack of familiarity with the scientific literature.  And, it is important to point out that the community and physicians have not been informed about symptoms of pesticide poisoning, and no program was put in place for physicians to report health consequences.  If your eyes and ears are closed, the information indeed will not get through.

    And finally about the testimony before the Council, it is not necessarily the case that the "poison is in the dose" or that the "dose makes the poison," as inverted dose/response relationships are present in some situations.

    Indeed, as Dr. LeStourgeon explains "in classical toxicology the phrase 'the poison is in the dose' is applicable only for subthreshold doses of an acute toxin.  Since dose/response curves for mutagens extrapolate to zero [straight line dose-response curve that shows no 'threshold.'  In other words the line is straight down to background] one must conclude that a single molecule of mutagen may induce a single mutation.  It is important here to point out that the patient never feels the mutation and thus usually concludes there is no problem."  We have previously commented about dose considerations, with details more specific to this district, and we explicitly noted the example that "Dioxin is yet another chemical group that has some effect at any measurable dosage."

    As another example of commentary by local officials, on NPR's "Insight" radio program, July 31, 2007, in the context of statements about use of pesticides in places such as the city, the home, and on golf courses, Trochet said "I do not accept the argument that it is OK to use pesticides for these reasons, but it is not OK to use the small amount of pesticide that is so far as we can tell safe in the amounts used to prevent some people from getting life-threatening disease.”  [Emphasis ours]  There are a number of troubling things about this statement, in addition to the unsupported assumption that the amount of the pesticide used is so small that it is safe.  Many people would not accept that it is OK to use pesticides in the amount used in the other contexts either, particularly if they were aware of the facts presented by Professor LeStourgeon.  Furthermore, there is no evidence whatsoever that using this pesticide will prevent anybody from getting the life-threatening disease about which she speaks – the neuroinvasive form of West Nile disease – and, again, only a very small fraction of the population becomes infected with WNv, only 1 in 150 of those people get the neuroinvasive form, and only a fraction of those die.  In 2007, the chances of a citizen getting the neuroinvasive disease in all of California were a little over 4.3 in 1,000,000 (156 neuroinvasive cases in a state with over 36,000,000 people).  Whatever Trochet's motivations are, the comments about the extremely rare neuroinvasive disease serve to scare people.  As we have insisted from the start, our citizens deserve public health based on facts and not fear.

    We do not accept the argument Trochet is essentially making: that we are awash in pesticides, so what does a little more matter when we spray populated areas?  We believe that the increasing cancer rate, the cumulative exposure, and the other disturbing scientific facts presented by Dr. LeStourgeon and others are a wakeup call to use far less pesticides in far less volume than we are doing now in all areas, without needlessly adding to the total, particularly when the pesticide is completely ineffective at slowing or stopping WNv.

Resolving the Conflict
– the Science.

    Certainly the critical question for local officials is what evidence they can supply to support their position.  And, by evidence we mean rigorously refereed studies by independent scientists in legitimate scientific journals, as opposed to review and publication in a growing number of "company" journals supported by the chemical, oil, pharmaceutical, pesticide, and other industries, with either non-scientists or acolytes supplying the reviews.  To date, vector control officials have supplied no such references to us, either about the safety or the efficacy of their aerial ULV spray program over populated areas.  The "Insight" program of July 31, 2007, and the Sacramento City Council meeting of August 9, 2007, were classic cases in point – numerous assertions were made about safety, efficacy was assumed, but no specific references were offered, other than repeated mention of the fatally flawed 2005 Sacramento study about efficacy, an excellent example of a "company" study in a "company" journal.  Indeed, in her testimony before the Sacramento City Council, noted above, Dr. Trochet says that she knows of no low-dose studies about risk – they would almost not be "worth the money."

    To the contrary, for his testimony before the Metro Board of Public Health, Dr. LeStourgeon supplied a packet containing a large amount of scientific information, accompanying the cover letter mentioned above.  Abstracts and short articles are posted here.  The appendices are as follows:

Appendix I:  A brief explanation of the SEER program as administered by the National Cancer Institute, a high quality national database that is of great value because it allows epidemiologists and cancer researchers to see trends in cause, incidence, diagnosis, and therapy over a relatively long time span.  Also, data from the National Cancer Institute that emphasize that pollutants, toxins, and endocrine disruptors continue to exist as an increasing threat to all citizens, supporting the points in the cover letter. 

Appendix II:  Abstracts of peer-reviewed published research in legitimate scientific publications dealing mainly with the genotoxicity of piperonyl butoxide (PBO), the synergant used in (and 60% of) the mix sprayed aerially by SYMVCD, clearly demonstrating the chemical's ability to induce mutations and/or modify normal patterns of gene expression and natural biochemical pathways.

Appendix III:  Abstracts of peer-reviewed published research in legitimate scientific publications dealing mainly with the estrogenic and general endocrine disrupting properties of Sumithrin, a pyrethroid.  The pyrethroid Deltamethrin is sprayed by backpack by SYMVCD, and David Brown stated to the Sacramento City Council on August 9, 2007, that what is sprayed by air and what is sprayed on the ground in this district have "no real difference" (at 30:04 into the meeting).

Appendix IV:  An abstract and two articles.  The abstract is that of a pesticide-industry funded research project.  It has been quoted by the pesticide industry in public forums while the papers presented in Appendices II and III are almost always ignored.  Only one of the chemical isomers that make up Sumithrin was tested, Sumithrin itself was not tested, and the method used here has failed to yield positive results with well characterized estrogenic compounds like bisphenol-A.  The two articles are about the special vulnerability of children to carcinogens and the ever increasing chemical pollution and ever increasing cancer incidences around the world.

Appendix V:  Abstracts of four classic review articles that document the evidence that 95-98% of all cancers are caused by somatic mutations in the genes that control cell growth. 

    There seems to be some confusion about the difference between pyrethrins and pyrethroids.  Dr. LeStourgeon clarifies: "Pyrethroids are synthetic pyrethrins.  Pyrethroids are much cheaper to make and have a similar chemical structure to the natural pyrethrins and similar biological activity.  Often they are designed to have more lipid solubility, as lipid soluble chemicals pass into cells more readily and often they are more volatile." It is important to keep in mind that 60% of the aerail spray mixture, Evergreen 60-6, is PBO, and 34% consists of unknown, "inert," ingredients, which are not inert in the usual sense of the word; often they are neither chemically, biologically, nor toxicologically inert (NCAP). 

    A 2006 paper studies the pyrethroid Bifenthrin, and the authors come to the conclusion that "exposure to bifenthrin, even at 'acceptable' limits, can increase the risk for and frequency of inflammatory responses and diseases such as asthma" (emphasis ours).  Additionally, a study published in the September 15, 2008, issue of Environmental Science & Technology has found pyrethroid contamination in 100 percent of urban streams sampled.  Beyond Pesticides notes that "California is currently reevaluating certain pyrethroid-containing pesticides as a result of increasingly conclusive research."

    As reported by Beyond Pesticides, the World Health Organization recently released a report about "children's heightened vulnerability to chemical exposures at different periods of their growth and development," noting that "children are not just small adults" and ". . .  over 30% of the global burden of disease in children can be attributed to environmental factors, including pesticides."  The report "highlights the fact that for children, the stage of their development when chemical exposure occurs may be just as important as the magnitude of the exposure. With respect to pesticides, the report cites several studies that tie pesticide exposure during key periods of development to neurobehavioral problems, Parkinson’s disease, and immunotoxicity, including respiratory diseases" (emphasis ours).  This of course means that "the poison is in the dose" is even less true for children than for adults.

    Along these lines, a September 2008 study indicates that "low-dose, short-term exposure to esfenvalerate, a synthetic pyrethroid pesticide, delays the onset of puberty in rats at doses two times lower than U.S. EPA’s stated no observable effect level," according to an article from Beyond Pesticides.  The researchers conclude that "This could potentially affect current established exposure levels for humans, because the reference dose for [esfenvalerate] of 0.02 mg/kg/day is based directly on the rodent NOEL of 2.0 mg/kg/day."

The Pseudo Science.

    As we have become more familiar with the very compelling science on this issue and at the same time observed public officials seemingly ignore it, we have been perplexed about why this might be happening.  It strikes us that it is possible that public officials lack the experience and/or knowledge to move from a possibly successful rural control program to handling a perceived urban problem, particularly since somebody like Vicki Kramer, Chief, Vector-Borne Disease Section of the CDPH, attached her name to the fatally flawed report without having any of the raw data (she supplied no data whatsoever in response to a formal Public Records Act request).  Her qualifications list a PhD in entomology from UC Berkeley, but a degree in entomology is not needed to see the fatal flaws.  This also hearkens back to the apparent lack of knowledge about DDT on the part of Dr. Trochet.

    Some skeptics have suggested that public officials might ignore the science because of influence by various commercial interests, and we have indeed begun to observe the new pseudo-scientific "company" journals that publish fatally flawed reports, the corporate influence in public agencies, etc.  And, the disagreements over proper public policy are nothing like honest scientific disagreements that occur among dedicated scientists; rather, they amount either to blatantly ignoring good science, to not having made the effort to become familiar with it, or to conjuring up studies that do not meet rigorous scientific standards.  Note, for example, when local officials first sprayed Sacramento in 2005 they were not even aware of what they now call the "encephalitis mosquito," which they now insist, well after the fact, is the main threat here.  They also completely mischaracterized the differences in what is done in Washington, D.C. (very effective control without aerial spray) and what is done here.  Furthermore,  they submitted the "Louisiana paper," essentially an administrative report and not scientific evidence, when they were questioned about their justification of the spray.  And of course they continue to offer up the fatally flawed Carney report as their main example of "peer reviewed evidence."

    As to influence by commercial interests, an August 16, 2008, article in the Washington Post, gives a good example of how the chemical industry controls agencies like the FDA, relative to a timely issue for those of us in this district, the use of BPA, given the capitulation to that industry by our own Legislature on SB 1713 and SB 1313 on August 18, 2008.  This was due to "an avalanche of lobbying" and "heavy-handed efforts to pressure [legislators] to vote no," according to the Sacramento Bee story.  As to some industry brochures opposing one of the bills, Assemblywoman Lois Wolk said "It is an extremely deceptive tactic, and I think . . . we ought not to reward the American Chemical Council by rejecting this bill." 

    Who is being rewarded by indiscriminate spraying of populated areas with ineffective pesticides for the purported control of WNv?

    It is important to note that representatives of a large number of EPA scientists recently sent a letter to the Administrator of the US EPA complaining that they were being coerced into making false and misleading safety claims regarding pesticides.  They said "We are concerned that the Agency has lost sight of its regulatory responsibilities in trying to reach consensus with those that it regulates, and the result is that the integrity of the science upon which the Agency decisions are based has been compromised," and "Our colleagues in the Pesticide Program feel besieged by political pressure exerted by Agency officials perceived to be too closely aligned with the pesticide industry and former EPA officials now representing the pesticide and agricultural community."

    Certainly a classic case of influence on marketing by pseudo science is given in the history of the tobacco industry.  After years of accusations of lies and coverups, including dubious testimony before Congress by top-ranking company officials, an article entitled "Tobacco firms' smoking gun revealed" in the October 19, 2007, Issue of Dateline UCDavis, reports that "after combing through nearly 50 million pages of previously secret, internal tobacco-industry documents, UC Davis and UC San Francisco researchers say they have documented for the first time how the industry funded and used scientific studies to undermine evidence linking secondhand smoke to cardiovascular disease."  See the full article, "Tobacco Industry Efforts Undermining Evidence Linking Secondhand Smoke With Cardiovascular Disease," in "Circulation," a Journal of the American Heart Association. 

    Is the pesticide industry now where the tobacco industry was years ago?

    After years of dealing with studies of varying quality about safety of pesticides, in a handout from his advanced course, Molecular Biology 273 (page 80 of the catalog), Professor LeStourgeon refutes the major arguments of the industrial conservatives.  And, in a careful piece containing some concentration analogies he candidly asks if "these 'conservative' groups care about my health or 'conserving' their profit margin."  We have previously noted Dr. Trochet's connections to the chemical and pesticide industries.  Also, David Brown is the 2008 president of the Mosquito and Vector Control Association of California (MVCAC), which lists "effective legislative advocacy" as part of its mission and lists a collection of 14 associated "vendor sites" on its web page.

    Finally, there is growing concern in the scientific community about restoring scientific integrity.  See the discussion on the web page of the Union of Concerned Scientists, for example, in which they note that relative to our impressive history of respecting the independence of scientists " . . . recent actions by political appointees, however, threaten to undermine this legacy by preventing the best available science from informing policy decisions that have serious consequences for our health, safety, and environment."  They discuss the growing problem and give important examples of such things as interference at the EPA.

Risk/Benefit Analysis.

    Dr. Trochet says that she cannot say "with certitude" that there is no risk from the spray.  Indeed, she cannot.  However, she then says that she can say "with certitude" that if we don't spray there will be death, neuroinvasive cases of the disease, and people paralyzed for life.  This is simply false – those rare events are not guaranteed if we don't spray, and if they are on the horizon the spray certainly will not stop them.  Indeed, with at most only four cases of neuroinvasive disease in the Sacramento area this year (2008) and no deaths tens, if not hundreds, of thousands of people were sprayed with "very potent" chemicals.  Officials might try to take credit for the almost non-existent case count because of the spray of South Sacramento, but there is no scientific evidence to support that contention.  And, without spray there has been very little sign of infection at all in Yolo County this summer and zero WNv cases of any kind.  This is not an aberration – it is completely consistent with the very low infection levels of such a disease as it naturally moves into what is called chronic endemicity after a few more active early years in a region.

    Any responsible "public health intervention" must undergo a risk/benefit analysis.  Public officials unfortunately have this one exactly backward.  They assume, in absence of any scientific evidence, that the spray works and there are thus benefits.  There is simply no evidence for that assumption.  They then assume that the risk of the spray is less than the risks of not spraying.  That is not possible – no benefit from the spray means that there is no risk not to spray.  The facts of the matter are that there are immediate risks for a certain segment of our population, such as people with asthma or Parkinson's disease, and there are long-term risks for all of us in terms of the new mutagens added to our environment and the mutational load that a number of us will suffer from spraying "very potent chemicals" over populated areas.

    If local officials can put aside the pseudo science, and if any benefits of the aerial ULV spray are ever demonstrated scientifically, an accurate risk/benefit analysis can be done, unless officials have either begun to use other means to combat the already small and steadily diminishing threat (see the comparison to Western Equine Encephalitis in the Summary) or begun to allow the virus to run its course like some other districts do.   We strongly support methods such as effective, risk-free, and long-lasting biological controls, for example.  With a scientific demonstration of efficacy of spraying the actual benefits could then be weighed against the very clear risks of spraying and the rarity and very mild nature of the disease for the vast majority of people.  However, at present the science of the matter shows that there is no demonstrated benefit, there are distinct short and long-term risks, and for the safety of our citizens the aerial ULV spray program of the SYMVCD should therefore be terminated.

Further References about Dose

•  Why the Adage 'the Dose Makes the Poison' Can Be Toxic to Corporate Chemicals Policy.
•  Does "the dose make the poison?"
•  Are all things poison? Rethinking safety standards for low doses of chemicals.
•  Time to Update Environmental Regulations: Should public health standards for endocrine-disrupting compounds be based upon sixteenth century dogma or modern endocrinology?
•  Dose Doesn’t Always Make Poison.