Phosphine Toxicity: Ethical Questions

Referencing: The Tobacco Industry and Pesticide Regulations: Case Studies from Tobacco Industry Archives

In their article McDaniel et al. (2005) presented three case studies, one involving an evaluation by Sciences International, Inc. (Pepelko et al. 2004), of which I am the president and CEO. This case study was related to the reregistration of phosphine by the U.S. Environmental Protection Agency (EPA). McDaniel et al. (2005) make two principal accusations: a) that I improperly used my status as editor-in-chief of Risk Analysis: An International Journal (Risk Analysis) in the publication of an article on phosphine toxicity, and b) that work done by Sciences International led the U.S. EPA to make an improper decision about phosphine risk. There are serious misrepresentations and omissions in this article. Also, neither the authors nor EHP contacted me before posting of the article.

Sciences International was engaged in 1998 by a coalition of companies with an interest in the fumigation uses of phosphine to provide an evaluation of phosphine acute toxicity for consideration in the U.S. EPA phosphine reregistration process. The membership of the coalition was diverse, representing industries in food processing, grain milling, rail transportation, and tobacco.

Based on this work, an article was published by scientists at my firm in 2004 on the toxicity of phosphine in Risk Analysis (Pepelko et al. 2004). The article was published 5 years after the U.S. EPA made their decision (U.S. EPA 2001) and presented a somewhat more conservative conclusion than that presented by the U.S. EPA. Quite contrary to the impression given by McDaniel et al. (2005), this article went through a thorough peer review and was handled properly in all respects. As a matter of policy, when I, or any member of the editorial staff for Risk Analysis, have a potential conflict of interest, we recuse ourselves from the review. Therefore, to avoid any conflict of interest, I asked Curtis Travis, the editor-in-chief emeritus of Risk Analysis, to handle the review of the two articles that were submitted in 2002, after the reregistration decision for phosphine. Travis sent the draft articles to independent reviewers and ultimately rejected both articles. His comments included the recommendation to consolidate them into one article. We submitted a revised and consolidated article in 2003, again handled by Travis; the article was accepted and published in October 2004 (Pepelko et al. 2004). McDaniel et al. (2005) made an issue of a suggestion I made that the article (Pepelko et al. 2004) could be expedited in the publication process. It is not uncommon for journals to expedite articles that are of timely interest, such as being relevant to a current decision and particularly in cases of new scientific developments. However, the phosphine article (Pepelko et al. 2004) was ultimately never expedited, a fact that McDaniel et al. did not mention after making the initial accusation. Our article (Pepelko et al. 2004) was handled properly and professionally in all respects.

Secondly, McDaniel et al. (2005) implied that the U.S. EPA improperly selected its uncertainty factors for the phosphine risk assessment based on the analysis done by Sciences International. McDaniel et al. did little to make the case that the U.S. EPA's decision was improper, other than to point out that not everyone agreed about it. It is notable that our article (Pepelko et al. 2004) recommended an exposure standard of 0.1 ppm, which is lower (more stringent) than the U.S. EPA's earlier decision (U.S. EPA 2001), and also lower than the standards set by the American Conference of Governmental Industrial Hygienists (ACGIH 2000), the Occupational Safety and Health Administration (OSHA 1999), and the National Institute for Occupational Safety and Health (NIOSH 1997). As described above, our article went through a rigorous peer review and represents a significant scientific contribution; slight scientific differences are not unusual, given the uncertainties involved in setting acute toxicity standards.

McDaniel et al. (2005) provided little description of the ultimate regulatory decision made by the U.S. EPA in regard to phosphine (U.S. EPA 2001), which is necessary to provide context to this discussion. The changes made to phosphine usage were significant, including the requirement for site-specific fumigant management plans, training and certification requirements, and additional label modifications to reduce harmful exposures. These changes represent a significant change in how phosphine is used, substantial requirements and burdens for users, and significant public health protections.

There are legitimate scientific issues that require resolution for setting safe acute toxicity levels, for example, for substances of interest for homeland security. Differing durations of exposure and the accompanying severity of effects present a challenge for evaluating health effects associated with short-term, acute exposures. Investigative tools, including the use of categorical regression and the regional gas-dose model for extrapolating from rat inhalation studies to humans, have been explored by the U.S. EPA and Sciences International for their utility in defining safe acute toxicity levels (U.S. EPA 1994, 2000); the applications of these approaches have been investigated for their utility in setting acute toxicity standards for phosphine. McDaniel et al. (2005) did not attempt to address these challenging scientific issues.

McDaniel et al. (2005) made no attempt to further scientific knowledge; therefore, their article appears to fall short of the scientific standards of EHP.

The author is the president and chief executive officer of Sciences International, Inc., which provides services to clients in the public and private sectors and trade associations; she has received funding from the Phosphine Coalition for previous work but received no financial support for writing this letter.

Elizabeth L. Anderson
Risk Analysis: An International Journal
Alexandria, Virginia
E-mail: elanderson@sciences.com

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Phosphine Toxicity: McDaniel et al. Respond

We appreciate the opportunity to respond to Anderson's letter. We do thank Anderson for providing details on the review process for the article eventually published in Risk Analysis (Pepelko et al. 2004) that was based on Sciences International's work for the Phosphine Coalition. In our article (McDaniel et al. 2005), we did not accuse Anderson of improperly using her status as editor-in-chief of the journal in the publication process. Instead, we point out that she suggested--in a 1999 memorandum to Phosphine Coalition member Joel Seckar--that the peer-review process for the paper couldbe expedited (Anderson 1999). We then pointed out that the article was ultimately published in 2004. We did not conclude from this that the paper was improperly handled. Indeed, we assumed that it was not, given the 5-year delay between the 1999 proposal and the 2004 publication date. Anderson notes that "it is not uncommon for journals to expedite articles that are of timely interest." However, we would question whether it is or should be accepted practice for editors who are also authors to initiate an expedited process for their own papers, or to suggest that they would be willing to do so in order to advance the interests of a regulated industry that has hired them in the context of regulatory deliberations.

In addition, we did not state in our article (McDaniel et al. 2005) that the work done by Sciences International led the U.S. Environmental Protection Agency (EPA) to make an improper decision about phosphine risk. We stated that the Phosphine Coalition hired Sciences International to write a report challenging the scientific basis of the U.S. EPA's proposed risk mitigation measures, focusing on reducing or eliminating the interspecies uncertainty factor that led to the U.S. EPA's proposed exposure level of 0.03 ppm (Seckar 1999). Sciences International did so; we offered evidence to show that a) an early draft was deemed too uncertain and tentative by members of the Phosphine Coalition and was revised by Sciences International to strengthen the language; b) the interim report submitted by Sciences International to the U.S. EPA was judged in a memorandum by a U.S. EPA toxicologist (Barolo 1999; Sciences International 1999a, 1999b) to lack the human data necessary to justify eliminating the interspecies uncertainty factor (Whalan 1999); c) the U.S. EPA made its final decision on the risk mitigation measures in December 1999, before receiving the final revised report from Sciences International (Sharp 1999). The conclusion we drew from this evidence, which we believe is reasonable regardless of the outcome of the decision itself, is that the U.S. EPA's regulatory decision making needs to be more transparent. If the U.S. EPA had provided us with the additional internal documents we requested, we might have been able to better understand how the agency made its final regulatory decision, one that left the existing worker exposure standard in place and failed to add community buffer zones and notification requirements as originally proposed.

Anderson suggests that, in our article (McDaniel et al. 2005), we should have examined such challenging scientific issues as categorical regression and the regional gas-dose model for extrapolating from rat inhalation studies to humans. This was not the focus of our work. We examined cases in which the tobacco industry intervened to influence aspects of the pesticide regulatory process. In the case of phosphine, our focus was on the proposed risk mitigation measures that were deemed of primary concern for the tobacco industry: the more stringent worker exposure standard, the buffer zone, and the notification requirements. All of these public health protections were adamantly opposed by the industry coalition, and none of them survived in the final regulatory decision.

We regret that Anderson attacks EHP in responding to our article (McDaniel et al. 2005). Our work underwent several levels of peer review before its publication; obviously, we believe that it advances knowledge regarding important regulatory processes--processes that, for good or ill, are both sociopolitical and scientific as they unfold, and in which we believe many EHP readers have interest. As we pointed out in our conclusion, although others have charged that agencies responsible for protecting human health and the environment are unduly influenced by the industries they regulate, it is rare to be able to study this process from the perspective of the regulated industry. The tobacco industry documents provide a unique opportunity to identify tactics that industry applies to a regulatory agency when trying to influence the outcome of a decision. The fact that these documents were prepared at a time when their eventual public disclosure was not anticipated raises their archival evidentiary value above what might be learned from contemporaneous interviews years later with persons whose economic interests were at stake in the events discussed. We stand by our interpretation of the documentary record.

P.A.M. and R.E.M. declare they have no competing financial interests. G.S. is employed by the Natural Resources Defense Council, an environmental nonprofit organization with an interest in ensuring that regulations of toxic chemicals are as health-protective as feasible.

Patricia A. McDaniel
Center for Tobacco Control Research and Education
University of California
San Francisco, California
E-mail: patricia.mcdaniel@ucsf.edu

Gina Solomon
Natural Resources Defense Council
San Francisco, California

Ruth E. Malone
Department of Social and Behavioral Sciences & School of Nursing
University of California
San Francisco, California

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