Tobacco is a heavily pesticide-dependent crop. Because pesticides involve human safety and health issues, they are regulated nationally and internationally; however, little is known about how tobacco companies respond to regulatory pressures regarding pesticides. This article analyzes internal tobacco industry documents and US Environmental Protection Agency (EPA) documents obtained through Freedom of Information Act requests to describe industry activities aimed at influencing pesticide regulations, focusing on cases involving methoprene, the ethylene bisdithiocarbamates (EBDC), and phosphine. The documents analysed here suggest that the tobacco industry can exert considerable influence over the pesticide regulatory process. 

Methoprene
In 1974, Philip Morris (PM) formed a partnership with the chemical company Zoecon to market a new insecticide. The active ingredient, methoprene, acted on cigarette beetles and tobacco moths as an endocrine disruptor, preventing their larvae from maturing1. PM pledged to assist Zoecon in introducing methoprene ‘in as many countries as we can’2. Some countries have regulations that require the establishment of maximum residue limits (MRLs) for pesticides on crops; however, PM determined that MRLs were not required in all countries, especially for pesticides on non-food crops such as tobacco3. PM asked Zoecon ‘to not force this issue and submit for MRLs when not required’4. In April 1991 Zoecon alerted PM’s director of research that the Malaysian pesticide board had recently set a MRL of 1.0 parts per million (ppm) for methoprene on tobacco5. Zoecon considered 1.0 ppm to be too low to enable the effective use of methoprene; the level supported by the labelled application rate was 10 ppm6. PM requested that Zoecon ask for an even higher MRL of 15 ppm to allow for application errors7,8. Zoecon representatives met with government authorities and requested a change to 15 ppm9. A Zoecon representative informed PM that, ‘in order to avoid surprises of this nature in the future’, he had directed Zoecon’s pharmaceutical group to obtain information from health authorities in other countries regarding the commodities for which methoprene tolerances were assigned. Assigning this task to the pharmaceutical group instead of the pesticide group, he wrote, ‘will not arouse the curiosity of the health directorates and will allow us to keep our promise to the tobacco industry, namely, that we won’t initiate queries that may cause the health authorities to direct attention to tobacco’10.In April 1992, George Lindahl of Zoecon faxed Bob McCuen, head of PM’s biochemical research, a letter outlining some of his concerns about PM’s approach to establishing MRLs for methoprene on tobacco11. In regard to Zoecon’s effort to establish an MRL of 15 ppm in Malaysia, he explained that: ‘I know we simply argued this case without any data to support our request. In more advanced countries, this tactic will not succeed … [A]ll our data demonstrate the need for a 10 ppm MRL. If a higher value is desired then we will require data from real field operations showing that a worse [sic] case scenario for faulty application will result in a 15 ppm residue, and hence the need for this value.’12 In a fax following this one, he asked PM to provide such data; a handwritten comment from a PM employee who reviewed the fax noted that ‘data doesn’t exist’13. Initially, the Malaysian authorities agreed to increase methoprene’s MRL to 10 ppm14; subsequently, it was raised to 15 ppm15. PM continued to advocate (through Zoecon) for MRLs of 15 ppm in Italy and Germany16.

EBDC Fungicides
In 1987, the US EPA initiated a review of EBDC fungicides, prompted by the agency’s determination that EBDCs’ breakdown product, ethylene thiourea (ETU), was a probable human carcinogen17. Anticipating EPA’s cancellation of many EBDC uses, US manufacturers voluntarily withdrew EBDC registrations for all but 13 food crops in 198918. In internal documents, the tobacco industry expressed concern that the EPA’s action could result in the ‘imposition of potentially crippling product residue tolerances’ in Europe19,20. EBDCs were regarded as vital to control blue mould outbreaks in Europe21. In October 1989, members of CORESTA, an international tobacco research organization with members drawn largely from the tobacco industry, established a sub-committee to ‘provide regulatory agencies with a sound basis for the development of tobacco agrochemical regulations’22,23. As discussed in a larger World Health Organization (WHO) report on tobacco industry influence at that agency, the sub-committee hired a consultant, Dr. Gaston Vettorazzi, to provide advice on influencing regulation24,25. Vettorazzi was a former WHO toxicologist and former technical secretary of the Joint Food and Agriculture Organization /WHO Meeting on Pesticide Residues (JMPR), an international meeting of scientists whose decisions often formed the basis of international law26. Selected partly for his ‘old boys’ contacts’27, Vettorazzi’s initial duties were to provide a review and analysis of toxicological data on EBDCs and ETU28. Vettorazzi’s initial review concluded that ETU was not carcinogenic or genotoxic29. Some of the tobacco industry scientists commented that this statement was ‘too strong in light of the NTP feeding studies’ – a reference to the US National Toxicology Program’s conclusion that animal studies showed clear evidence of ETU’s carcinogenicity30. Vettorazzi subsequently revised his conclusions, stating that ‘[ETU’s] toxicity, including carcinogenicity, can be explained by the known mechanisms of action characteristic of thyroid-function inhibiting agents’. Thus, he stated, a threshold could be set below which ETU did not cause thyroid tumors31. CORESTA authorized the distribution of Vettorazzi’s revised report to his former colleagues at WHO, once all references to tobacco and CORESTA were removed32. WHO’s JMPR was scheduled to review EBDCs/ETU in 1993; if this review were favourable, the tobacco industry would be assured continued access to EBDCs in Europe33. With CORESTA funding ($100,000 a year) and approval, Vettorazzi offered ‘to assist and help’ Dr. Herrman, of the JMPR WHO Secretariat, with JMPR toxicological reviews, without disclosing his tobacco industry ties34,35,36. Vettorazzi wrote and reviewed several working papers on compounds to be discussed at the 1992 JMPR, including the EBDC thiram37,38. One outcome of that meeting was the re-establishment, at a higher level, of the previously cancelled Acceptable Daily Intake (ADI) for thiram39. Vettorazzi continued his work with WHO in 1993, supplying his CORESTA-funded reviews to the adviser responsible for drafting the working paper that would form the basis of the September JMPR on EBDCs/ETU without revealing their sponsor. Vettorazzi also attended the September meeting as an invited ‘temporary adviser’40. The meeting’s outcome reflected Vettorazzi’s conclusions. In contrast to EPA, JMPR determined that ETU was not genotoxic, and thus raised the ADI level (from 0.002 to 0.004 mg/kg body weight)41. CORESTA considered this ‘a very positive result for the industry’, since it ‘clearly indicates that the “carcinogenicity” of [ETU] is not really a burning issue any longer’42,43. JMPR’s safety standard became part of international trade law, preserving tobacco industry access to EBDCs44. Soon after the JMPR meeting, CORESTA extended Vettorazzi’s contract for 18 months, listing one of his duties as ‘[providing] information about the activities of pesticide action groups’. He was to be paid another $100,00045. Vettorazzi continued working for CORESTA until at least 2001, when the organization paid him $30,000 to monitor international activities related to tobacco pesticide residues and registrations46.

Phosphine
Phosphine is a fumigant used on stored commodities, including tobacco and finished cigarettes, to kill insects. Because of the risks it poses, applicators are advised to wear respirators and protective clothing, and warehouses must be sealed to prevent leaks47. In December 1998, EPA proposed a series of 15 risk mitigation measures (RMMs) for phosphine including a threshold limit value of 0.03 parts per million (ppm) of phosphine during fumigation (reduced from the existing 0.3 ppm standard), the establishment of a 500-foot buffer zone around fumigated structures, and prior notification of all residents living within 750 feet of a fumigated structure48. The Tobacco Association of the United States, in a letter to EPA, stated that the economic burdens imposed by the RMMs would ‘make it virtually impossible for our industry to continue to fumigate stored tobacco’49. The Tobacco Association, RJ Reynolds (RJR), Philip Morris, and over 150 other organizations with a stake in the continued use of phosphine formed a lobbying group, the Commodity Industry Coalition for Phosphine Fumigation (the Coalition)50. RJR – represented primarily by toxicologist Joel Seckar – took an active role in the Coalition, assuming responsibility for challenging the scientific basis of EPA’s proposals51. Under his guidance, the Coalition hired Sciences International (Sciences), a consulting firm specializing in health and environmental risk assessment, to provide research to support existing standards52. Sciences was headed by Dr. Elizabeth Anderson, a former director of the Carcinogen Assessment Group and the Office of Health and Environmental Assessment at EPA53. To support the Coalition’s assertion that the proposed exposure level of 0.03 ppm was too conservative, Sciences focused on the interspecies uncertainty factor. EPA had first determined from a published subchronic toxicity study of rats that there were no observed effects attributable to inhaled phosphine at 3 ppm54. To extrapolate to humans, EPA had then used two ten-fold uncertainty factors – one for intraspecies variability and one for interspecies variability – to arrive at a maximum exposure level of 0.03 ppm55. Documents indicate that Sciences’s strategy was to convince EPA that the interspecies uncertainty factor was unnecessary; showing that a number of animal species reacted in the same manner to phosphine would suggest that humans were similar enough that the interspecies uncertainty factor could be removed56,57. This would leave only the intraspecies factor of 10, which would result in a maximum exposure level for humans of 0.3 ppm, the existing standard.In June 1999, Sciences submitted a first draft of its phosphine toxicity review to some Coalition members58. A reviewer from the Coalition’s lobbying firm pointed out that the animal studies cited did little to support the idea that the interspecies uncertainty factor should be eliminated ‘since most [of the animals] appear to be rat or mouse strains with similar breathing characteristics’59. Instead, the studies cited by Sciences seemed to support the idea that phosphine called for a conservative standard, as they indicated that ‘phosphine is a very toxic material to most species tested’60. Another commenter noted that the uncertain and tentative tone of the report ‘will trigger concerns by EPA and they will say “if [an] expert in the field states that there remains great uncertainty, maybe we are on solid ground by being very conservative”’61. Sciences staff revised the report, removing tentative statements and asserting that their work to date supported reducing the interspecies uncertainty factor to 1 (effectively eliminating it), thus preserving the existing exposure standard of 0.3 ppm. They submitted this revised interim report to EPA in July 199962. At a Coalition meeting that same month, Coalition consultant Dan Barolo, former director of EPA’s Office of Pesticide Programs, reportedly urged members to speed their efforts because ‘phosphine is quite hazardous if used improperly. The more the Coalition slows the process, the greater the chance for an accident with possible fatalities, which would send EPA back into conservative mode and make it far more difficult for them to publish reasonable RMMs’63.

In August, John Whalan, a toxicologist at EPA’s Health Effects Division, summarized in a memo his analysis of Sciences’s interim report64. He noted that ‘there is no precedent for using an [interspecies uncertainty factor] of one when establishing … a regulatory value in the Health Effects Division. The only time an interspecies [uncertainty factor] is not applicable is when human data are used. The available data do not support deviating from Agency policy, and the Coalition did not provide any new data.’ He also pointed out that Sciences’s review of animal studies, intended to show that phosphine toxicity was relatively constant across species, was largely ‘irrelevant’, since it did not include a comparison of toxicity for a small versus large mammal.

Although Sciences had not yet submitted to EPA its full report on phosphine, in December 1999, EPA made its final decision65. They mandated a ‘fumigation management plan’ like that proposed by the Coalition66. The agency also eliminated the interspecies safety factor leaving the old 0.3 ppm standard, on condition that phosphine registrants conduct additional research if Sciences’s review was found inadequate67. A Coalition member noted ‘[i]t is important to point out that this additional work will take years and that the current 0.3 ppm threshold will stay in place during that time’68. RJR credited its leadership on the science with saving the company ‘many millions of dollars’69.ConclusionThese case studies provide insight into tactics that the tobacco industry applies to a regulatory agency when trying to influence the outcome of a decision. These tactics go significantly beyond the usual approaches – such as participation in public comment periods and public meetings – to influence scientific and regulatory decision-making. This article also raises questions about industry influence over regulatory agencies. In the case of WHO deliberations on EBDCs, the tobacco industry coordinated covert actions, hiding the financial ties and involvement of CORESTA. Rigorous disclosure requirements and oversight might have allowed WHO’s agencies to judge more accurately the potential for bias related to conflicts of interest. In the case of EPA’s review of phosphine, a regulatory agency appears to have been quite willing to cooperate with the industry and its consultants. Protection of the public interest hinges on an open process and regulatory agencies’ willingness to stand up to pressure from regulated industries. When these are in doubt, public confidence in the fairness and efficacy of regulations may be unwarranted. The resource disparities between powerful industries and public health organizations may make it difficult to ensure that the public interest is fairly represented, particularly when discussions occur behind closed doors, as apparently occurred at EPA. Increased public and media scrutiny of these processes could help ensure that public health considerations are weighed at least as heavily as commercial ones.

Finally, given the deadly epidemic of tobacco-caused disease, which kills an estimated five million people annually worldwide70, is it in the public interest for regulatory agencies today to continue facilitating standards that make it easier and less costly to grow, transport, store, and manufacture tobacco products? 

Reproduced with permission from Environmental Health Perspectives. Complete article available at http://ehp.niehs.nih.gov/docs/2005/7452/abstract.html

Patricia A. McDaniel, PhD, is a Postdoctoral Fellow at the Center for Tobacco Control Research and Education, University of California, San Francisco, US, patricia.mcdaniel@ucsf.edu; Gina Solomon, MD, MPH. is a Senior Scientist at the Natural Resources Defense Council, San Francisco, US, and is Assistant Clinical Professor, Division of Occupational and Environmental Medicine, Univeristy of California, San Francisco, US, gsolomon@nrdc.org; Ruth E. Malone, RN, PhD, FAAN, is an Associate Professor and Director, Masters Specialty Program in Health Policy, and Core Faculty, Center for Tobacco Control Research & Education, Department of Social and Behavioral Sciences, University of California, San Francisco, US, ruth.malone@ucsf.edu.