How Industry Exploits the Limits to Science

Witholding Critical Data and Information

"...Dow Chemical sent a representative down to my lab a number of months ago and essentially asked if there were a mutually beneficial outcome that we could arrive at where I held off publishing the information about this chemical until they had repeated my studies, and after repeating my studies approval for publication was received by all the plastic manufacturers.

DH: They were trying to buy you off?

FvS: We didn't get to anywhere beyond that. My response was, "Do you have a scientific criticism that would justify not publishing this paper?" Because if anybody can ever provide a valid scientific criticism on the research that I've done, that would be a reason not to publish an article. But this was research funded through the National Institutes of Health. I have an absolute obligation to take public money and report the findings from research conducted with those public funds. To not do so would be a gross violation of professional ethics, and I don't need to tell you would be totally inappropriate.

So I don't know what mutually beneficial outcome they were thinking about, but there was no beneficial outcome that I would have found acceptable and so I simply shut that conversation off. But clearly that was an example where they would have preferred that the information not be seen by the general community, and not be discussed about in this format.

DH: Dow Chemical said this didn't happen. There may have been a misunderstanding, or whatever, but they certainly weren't trying to influence your research.

FvS: Well, if you say that Dow says this didn't happen, there were a number of other people in the room during this conversation and I wrote a letter to the Food and Drug Administration documenting the conversation in detail. Quite a detailed letter that was sent to the government with copies all through my university hierarchy. I never received a letter back from anybody at Dow suggesting that there was anything in that letter that wasn't exactly as it had happened which, again, was also witnessed by numerous other people. If they have any problem with what I am saying here, they can deal with that however they want. What I am saying is exactly what happened and could be corroborated by a number of other people who were in the room and heard this.

DH: Why would they do this?

The chemical industry has shown an absolute unwillingness to give any money not attached to strings where they control the process of putting together the experiments and then publishing the experiments. And that is just unacceptable. And this is a perfect example of what would happen if I had a contractual arrangement with them that allowed them to shut me down in terms of providing you with the information I am providing to you.

What we have been calling for, in the scientific community, for a number of years is for the chemical industry to set up a mechanism to give money to address the basic issues of how chemicals work without controlling the design of the experiments and the ability to publish the work once the research has been done..

[Interview with Frederick vom Saal, Ph.D, Professor of Biological Sciences, University of Missouri. Vom Saal is a leading researcher in the field of developmental biology
See: Interview conducted in February 1998 by Doug Hamilton, producer of FRONTLINE's "Fooling With Nature.
"http://www.pbs.org/wgbh/pages/frontline/shows/nature/interviews/vomsaal.html ]

The Strategy of Creating Doubt

Most agricultural chemicals have never been assessed. Pesticide studies - when they are eventually performed - are carried out on animals where the laboratory procedures are controlled. The results of those studies are extrapolated to humans living in the real world. Therefore the results are far from perfect. It is assumed that if something is caused in animals then it will have similar (if not identical) effects in people. But this is not certain. Further, scientists look to exposures in people that occur over the course of 20, 30 years or more. Since everybody has multiple exposures in their lifetime (and to a large number of toxins with some simultaneously) the answers are never precise. Scientists and regulators are faced with the question, how do you weigh the evidence, how do you make the best judgment based on the best current available evidence?

Industry groups are demanding certainty and precision with respect to the provision of proof that their products cause harm. They can do this because the onus of proof of harm has been placed on the human population exposed to these chemicals as well as the publicly-funded Government regulators. A 1997 judgement in the United Kingdom however has softened this hardline approach by introducing the concept that harm can recognised as having been done by a pesticide 'on the balance of probabilities' presented. This decision may herald an era of commonsense where the public no longer have to wait for a revolutionary scientific breakthrough that proves strict scientific causation of disease for each biocide implicated in incidents before adequate compensation is made available to victims.

References:
'OP damage - judge agrees'
http://www.pan-uk.org/pestnews/pn38/pn38p6.HTM 'NPR Manufacturing Science
http://www.thecre.com/quality/2005/20050807_quality.html 'Bush Stacking Science Panels'
http://www.albionmonitor.com/0301a/bushsciencepanels.html

Toxic Below Limits of Detection

FvS: "For some chemicals, and for some hormones, the technical capacity to measure them is actually less sensitive than the body's ability to detect them."

"...DH: You've said that the doses at which hormones affect the body are extremely low. Give me an example to make me understand that.

FvS: The issue of the amount of hormone that actually causes effects is very difficult for scientists to talk to people about because we're dealing with numbers that are outside of the frame of reference that anybody is going to be thinking about. We see changes, profound changes, in the course of development of essentially the whole body of experimental animals, and we're working with mice and rats, and we see these changes at fifty femtograms of the hormone per milliliter of blood. That's 0.05 trillionths of a gram of this hormone in a milliliter of blood.

DH: And what sort of effect does it have?

FvS: We see changes in the functioning of the prostate. We see dramatic change in the sprouting of glands within the fetal prostate. We see changes in testicular sperm production. We see changes in the structure of the endocrine control region in the brain, which is accompanied by changes in sex behavior, aggression, the way these animals behave towards infants, their whole social interaction, the way they age, the time that they enter puberty, the age at which they cease reproduction. It changes their entire life history, and these changes are capable of occurring at very low levels of hormones.

[Interview with Frederick vom Saal, Ph.D, Professor of Biological Sciences, University of Missouri. Vom Saal is a leading researcher in the field of developmental biology
See: Interview conducted in February 1998 by Doug Hamilton, producer of FRONTLINE's "Fooling With Nature.
"http://www.pbs.org/wgbh/pages/frontline/shows/nature/interviews/vomsaal.html ]

Autoimmunity hasn't been explored

Absence of Testing Protocols for Endocrine Effects

"Every independent peer-reviewed trial except one has found atrzine to have a castrating effect on frogs and fish. All the trials done by Syngenta to determine whether atrazine does have a chemically castrating effect on frogs have been dogged by breaches of laboratory protocols." [Source: ‘The cancer scare around a common chemical’ ,Australian Financial Review, Page 26. May 7-8, 2005.Author: Julie Macken]

However,

"A corn and chemical lobbying group has petitioned the U.S. Environmental Protection Agency (EPA) under the Act challenging the agency's right to include peer reviewed studies documenting endocrine disruption effects in its risk assessment of the herbicide atrazine. The group argues that the EPA has not yet established testing protocols to characterize endocrine effects.[Source: 'Critics Say 1993 Court Ruling Undermines Science', By J.R. Pegg.WASHINGTON, DC, June 23, 2003 (Environmental News Service)

How are Potential Endocrine Disrupting Chemicals Regulated Today?

Insufficient data to assess endocrine disruption for most chemicals - August 2005

"While EPA has some data on endocrine-disrupting pesticides, currently insufficient scientific data are available on most of the estimated 87,000 chemicals produced today to allow for an evaluation of of endocrine associated risks. To address this issue, EPA is developing a two-tiered screening and testing process." [Source: 'The Endocrine Disruption Screening Program', US EPA.
http://www.epa.gov/scipoly/oscpendo/edspoverview/primer.htm#3

The current status of assays to assess endocrine disruption can be found at: http://www.epa.gov/scipoly/oscpendo/assayvalidation/status.htm

The Regulation of Atrazine - a way to track a potential endocrine disruptor

European Union to ban Atrazine by early 2005

".. the European Union has announced it will ban it entirely by early 2005. ..

Reference: 'EPA Won't Restrict Toxic Herbicide Atrazine, Despite Health Threat'
http://www.nrdc.org/health/pesticides/natrazine.asp

NRDC files lawsuit against the US EPA over approval process for Atrazine - February 17th, 2005

"..the Natural Resources Defense Council (NRDC) filed a lawsuit against the U.S. Environmental Protection Agency (EPA) for holding upwards of 40 private meetings with atrazine's manufacturer, Syngenta, while the agency was conducting a special review of the herbicide to consider its impacts on amphibians and links to cancer in humans. That review resulted in EPA approving continued use of the herbicide in 2003."

"NRDC's recent legal challenge to EPA bears a remarkable resemblance to a similar lawsuit filed more than 20 years ago by the environmental organization, also charging EPA with making sweet deals with industry. As that case progressed, (the then) EPA Administrator Ann Gorsuch resigned amid allegations of improper industry influence, and the agency agreed to a strict criteria of open and transparent decision making around the re-registration or "special review" of pesticides. Those restrictions forbade EPA to make a final decision based on negotiations with industry and required a balance of perspectives in committees of outside advisors. The NRDC lawsuit charges that EPA has ignored these regulations in its regulation of atrazine."

Resources: Annual Data Report http://www.mda.state.mn.us/appd/ace/reports/2005annual.pdf; Press Release, Minnesota Center for Environmental Advocacy, http://www.mncenter.org; Press Release, Feb 17, 2005, NRDC, http://www.nrdc.org.

Reference: 'EPA Sweet on Atrazine'
http://www.ghorganics.com/Atrazine%20Ground%20Water%20Contamination.htm

EPA concludes atrazine unlikely to be a human carcinogen and opposes further review of the chemical - July 2004

"EPA has asked NTP to withdraw atrazine from review in NTP's 12th Report on Carcinogens. EPA's letter to National Toxicology Program points out that EPA has just completed its own multi-year review of atrazine and cancer. Based on EPA's review of all the best available evidence, EPA concluded that atrazine is not likely to be a human carcinogen. No new evidence will be available until several years from now, when ongoing epidemiological studies will be completed. EPA itself intends to review atrazine again when the new epidemiological data become available. Consequently, EPA believes there is "no merit" in NTP's proposed cancer review of atrazine for the 12th Report on Carcinogens." One of the objections put by the EPA is that the NTP failed to mention that the data from The National Cancer Institute (“NCI”) who are/were conducting an epidemiological study of agricultural workers, pesticide exposure, and cancer is not available. Noting that the study will not be complete until mid-2005 at the earliest.[Source: 'No Merit" in NTP Atrazine Review'
http://www.thecre.com/quality/20040726_regweek.html

Reference: 'EPA Won't Restrict Toxic Herbicide Atrazine, Despite Health Threat'
http://www.nrdc.org/health/pesticides/natrazine.asp

Reference: 'EPA Won't Restrict Toxic Herbicide Atrazine, Despite Health Threat'
http://www.nrdc.org/health/pesticides/natrazine.asp

FOI requests from NRDC re Atrazine approval fail - October 2003

" The National Resource Defence Council in the US filed a series of Freedom of Information Act requests with the White House and the EPA, which failed to produce relevant documents."

Reference: 'EPA Won't Restrict Toxic Herbicide Atrazine, Despite Health Threat'
http://www.nrdc.org/health/pesticides/natrazine.asp

NRDC files lawsuit against the EPA regarding its approval of Atrazine - August 2003

"..The US Environment Protection Agency (EPA) allowed Syngenta, the main manufacturer of atrazine, and other companies to continue to sell Atrazine in the United States with no significant restrictions. ..In a lawsuit filed in August 2003, NRDC charged the EPA with failing to protect endangered species from atrazine, despite having acknowledged that the weed-killer might cause widespread harm to endangered species. NRDC is calling on the EPA to fulfill its obligations under the Endangered Species Act and ban atrazine from the market. NRDC has also asked Syngenta to hand over to the EPA, and to make readily available to the public, any other data it may have on atrazine's health effects...

Instead of addressing the water contamination issues, EPA developed an agreement with Syngenta, on reapproval of Atrazine, to conduct a monitoring program in 40 watersheds, fewer than 4 percent of the 1,000 streams identified by the EPA as being at highest risk for atrazine contamination.

"..an August 2003 report from the EPA's independent scientific advisory panel noted that atrazine exposure could not be ruled out as the cause of cancers observed in studies of the chemical..."

References: 'EPA Won't Restrict Toxic Herbicide Atrazine, Despite Health Threat'
http://www.nrdc.org/health/pesticides/natrazine.asp

EPA finally accepts limited public comments on draft guidelines for the Endocrine Disruptor Screening Program - March 2003

In March 2003, three and half years after its Congressionally-mandated deadline, the U.S. Environmental Protection Agency began accepting public comments on draft guidelines for the Endocrine Disruptor Screening Program (EDSP), a program to test chemicals for endocrine disrupting potential. In a controversial move, the agency proposed to exclude from the first round investigation chemicals with a known or suspected ability to disrupt hormones in humans and animals. The agency would also not accept public input on which specific chemicals should be reviewed.[Source: 'Endocrine Disrupting Chemical Program Released for Public Comment', March 17, 2003. Beyond Pesticides. http://www.beyondpesticides.org/news/daily_news_archive/2003/03_17_03.htm

UN Environmental Program lists Atrazine as a globally important persistent toxic substance - 2002

"In 2002 the herbicide, atrazine, was listed by the UN Environmental Programme as a globally important persistent toxic substance with the potential for regional transport. Measurable levels of the herbicide have been found in rain and fog in Europe as well as in the U.S., where atrazine has been detected at levels higher than EPA's safety standard in the drinking water serving more than a million U.S. residents."

Reference: 'EPA Sweet on Atrazine'
http://www.ghorganics.com/Atrazine%20Ground%20Water%20Contamination.htm

Dr Tyrone Hayes Atrazine studies report reproductive and other hormonal effects on frogs - 2002

In 2002, Dr. Hayes reported chemical castration (demasculization) and feminization of frogs at low but ecologically relevant concentrations of atrazine. This study, published in a peer reviewed scientific journal, was not the first performed by Hayes revealing atrazine's effects. Earlier work done by Hayes and his laboratory with funding from Syngenta was disputed by the agro-chemical giant and not published. Hayes duplicated his work independently, examining leopard frogs (Rana pipiens) across a transect of the U.S. extending from Utah to the Iowa/Illinois border, and detecting frog abnormalities similar to those found in his laboratory in every site where atrazine levels were over 0.1ppb. When Hayes' work was published, EPA was midway through a special review of atrazine. Syngenta continued to dispute Hayes' findings while also offering him two million dollars to continue his research in "a private setting."

Reference: 'EPA Sweet on Atrazine'
http://www.ghorganics.com/Atrazine%20Ground%20Water%20Contamination.htm

Note: Non-Guideline Studies by the US EPA show Atrazine has endocrine effects - November 2000

studies have been conducted that show that atrazine has reproductive and developmental effects that can be attributed to alterations in endocrine function." Draft Atrazine R.A., Part A, p.19. EPA further explained,

Adverse reproductive or developmental consequences have been identified following treatment of different strains of pregnant rats or neonates with atrazine or its metabolites. [T]his evidence does not come from results of EPA guideline studies but from results of special studies conducted with atrazine or its metabolites.

Two of these "special studies" use protocols that are not included among EPA's currently operative guideline tests: i.e., "'Research Protocol for Assessment of Pubertal Development and Thyroid Function in Juvenile Female Rats (U.S. EPA, 1998b...."; and "'Research Protocol for the Assessment of Pubertal Development and Thyroid function in Juvenile Male Rats (U.S. EPA, 1998b)." Draft Atrazine R.A., Part C, pp. 9-10. Both these test protocols are proposed as part of EPA's Tier I screening tests for endocrine effects in the Agency's Endocrine Disruptor Screening Program ("EDSP"). 63 FR 71542, 71551-52 (Dec. 28, 1998).

Thus, EPA is assessing atrazine's non-cancer risks using:

EPA is bound by its current operative non-cancer guidelines until EPA promulgates new validated and standardized non-cancer effects guidelines and tests in accordance with the APA, FQPA, and CRA. Neither atrazine nor any other substance can be regulated on the basis of tests for which "reliability and reproducibility" are still being evaluated.[Source: 'EPA is Improperly Using Proposed, Unvalidated Tests to Assess and Regulate Herbicides and Other Substances' published by The Centre for Regulatory Effectiveness. http://www.thecre.com/action/00-11-2.html

Syngenta begins funding Ecorisk to investigate Atrazine - 1997

"Since 1997, Syngenta has paid millions of dollars to Ecorisk, a Ferndale, Wash., company that does consulting and project management in toxicology, to investigate environmental issues related to atrazine. Ecorisk’s atrazine panel, which was headed by Texas Tech University toxicologist Ronald Kendall, planned, funded, and executed the atrazine studies criticized by Hayes.

At SETAC, Hayes attempted to prove his point by showing e-mail messages from Ecorisk researchers to himself and others. (Hayes was at one time a member of the Ecorisk panel, but resigned after a disagreement about the significance of his work.) Hayes says that he was driven to take this action because he is appalled that EPA would attempt to objectively evaluate data from Ecorisk scientists despite knowing that they had been dishonest, manipulated data, and conducted poor studies. Kendall, a well-known scientist who has served on many government advisory panels and committees, has denied Hayes’ allegations."

Hayes publicly contends that Syngenta manipulated EPA, managed the regulatory process, and subverted science to keep atrazine on the market. Meanwhile, the EPA SAP report released in October found fault with all the studies of frogs reported so far, calling the science “flawed”.

In a statement, EPA said it decided to re-register atrazine in part because the SAP report concluded that although amphibian studies, such as those from Hayes’ group, provide evidence to support the hypothesis that atrazine may affect amphibian development, they did not provide enough evidence to show that atrazine produces a consistent, reproducible effect on amphibian development. On the other hand, because of its adherence to the precautionary principle, the European Union has already banned atrazine.

The issue was hotly debated at the last Society of Environmental Toxicology and Chemistry (SETAC) meeting in November, where Hayes, a dynamic speaker, stunned a standing-room-only crowd of environmental scientists by declaring that the issue was about subverting, not advancing, science. Hayes said that he was driven to such a conclusion by industry efforts to muddy the scientific waters with sloppy, poorly designed studies that never attempted to replicate his work.

Reference: Science News - February 19, 2004. 'Controversy clouds atrazine studies'
http://pubs.acs.org/subscribe/journals/esthag-w/2004/feb/science/rr_controversy.html

The Prague Declaration on Endocrine Disruption(May 2005)

http://www.bio.uni-frankfurt.de/ee/ecotox/news/PragueDeclaration.pdf

"International experts and scientists representing many different disciplines came together in Prague on 10 – 12 May 2005 for a workshop on chemicals interfering with hormone systems, so-called endocrine disrupters. The workshop was convened to discuss recent European research on the health risks associated with these chemicals. Much of this work emanated from large research projects funded by the European Union, and joined together in the cluster for research on endocrine disrupters, CREDO. The results presented at the Prague workshop have reinforced concerns over the long-term consequences of exposure to endocrine disrupters to humans and wildlife....

13. A fundamental element of chemical safety assessment is the assumption of a threshold dose below which there are no effects. This may not be tenable when dealing with endocrine disrupters, because certain hormonally active chemicals act in concert with natural hormones already present in exposed organisms. Thus, even small amounts of chemicals may add to the overall effects, irrespective of thresholds that might exist for these chemicals in the absence of natural hormones. Additionally, due to limited sensitivity of established test methods, it is likely that effects are overlooked.

14. A further complication is that hormonal effects are often masked by other toxic responses. Only when testing is carried out at low doses usually not administered during routine testing do these effects become apparent. Furthermore, a feature of endocrine disrupters is the late occurrence of adverse effects long after exposure has ceased. Existing testing methods are not designed to deal with this possibility."

15. These difficulties are exacerbated when the effects of simultaneous exposure to many chemicals (mixture effects) are considered. Recent studies have shown that mixture effects can occur even when each component is present at a dose that individually does not produce effects. These observations further undermine the belief that threshold doses can be applied meaningfully during the safety assessment of chemicals. A dose of a single chemical judged to be safe after testing in isolation may give a false sense of security when exposure includes large numbers of other endocrine active chemicals.

16. The array of standardised methods that exists for the safety assessment of chemicals is ill-equipped to identify endocrine disrupters or to anticipate their likely effects on humans and wildlife. An inevitable consequence of these deficiencies has been that many pollutants now recognised as endocrine disrupters, such as the case of tributyl tin, estradiol and phthalates (used as plasticisers in consumer goods), were only identified through scientific studies, but not by routine safety testing. By this time considerable environmental damage had already been caused. Therefore, there is an urgent need to improve existing, and to develop novel, regulatory test methods.

17. Due to the weaknesses of existing regulations in identifying endocrine disrupters, biological and chemical monitoring programmes become increasingly important for the detection of as yet unidentified effects missed during the current risk assessment of chemicals. Existing monitoring programmes lack the ability to deal appropriately with endocrine disrupters, and chemical and biological monitoring must exist in concert.

18. Environmental exposure to chemicals is as a mixture, not a single agent. However, this is not reflected in testing, and provisions to take mixture effects into account are totally lacking. Recent research indicates that this may lead to a significant underestimation of risks. The issue is beginning to receive attention among regulators, but jointly, regulators and scientists need to cooperate to develop workable approaches to dealing with mixtures. Proposed measures and actions to be taken.

19. For the foreseeable future, regulation of endocrine disrupters will have to cope with the tension between the biological plausibility of serious, perhaps irreversible damage and delays in generating data suitable for comprehensive risk assessment. In view of the magnitude of the potential risks, we strongly believe that scientific uncertainty should not delay precautionary action for risk reduction....

And

What the Australian federal pesticide regulator (APVMA) has to say about a chemical strongly linked to endocrine disruption - Atrazine

"atrazine 'poses no undue hazard to most users', according to the Australian Pesticide and Veterinary Medicines Authority. However, this authority, responsible for registering and regulating agricultural and veterinary chemicals, is funded solely by the chemical companies it regulates. The federal government plans to make this dependence more complete by charging a levy on chemicals – which can then be directed to support the running costs of the APVMA.

Heffernan wants the APVMA audited. As the chairman of the Senate’s Rural and Regional Affairs and Transport Legislation Committee, he intends to ensure this happens. “We need to audit the APVMA to determine who they answer to, because it seems to have no real accountability at the moment,” he says.[Source: ‘The cancer scare around a common chemical’ ,Australian Financial Review, Page 26. May 7-8, 2005.Author: Julie Macken]