On to Other Things for a Moment – Another Perspective on the Petition from Hell

This doesn’t have the urgency of creating an effective disaster response mechanism on the heels of the Hurricane Katrina debacle, but I didn’t want this news to grow too cold. From Effect Measure, I heard about the American Council for Science and Health’s (ACSH) initiative to kneecap some of EPA’s regulatory efforts, by challenging the agency’s carcinogen assessment guidelines through its Quality procedures. The ACSH’s intellectual basis for their efforts is published in their book, America's War on "Carcinogens": Reassessing The Use of Animal Tests to Predict Human Cancer Risk. I haven’t purchased a copy yet (I will be reviewing it in a future post), and their petition for a Request for Correction wasn’t up on EPA’s web site when I checked last weekend, so I don’t know the specifics about their complaint. But those wouldn’t be hard to figure out (a summary can be found here). Other things that ACSH says on their web site about America’s War on “Carcinogens” is:

American consumers should not be subject any longer to the “carcinogen du jour” scares that have dominated the headlines for the past five decades. Corporations should not be forced to withdraw perfectly useful and safe products from the market (or take unnecessary efforts to purge chemicals from the environment) just because a substance is labeled an animal carcinogen. In our pursuit of methods to reduce the risk of cancer in America, science and common sense, not rhetoric, scare tactics, and hyperbole, should prevail.

In this book, scientists associated with the American Council on Science and Health call upon Congress, the National Cancer Institute, the National Toxicology Program, our nation’s regulators, scientists from many disciplines, as well as members of the media to step back from the familiar but scientifically baseless mantra that “if it causes cancer in animals, it must be assumed to be a human cancer risk.” Such a simplistic, unscientific, inconsistent approach to ferreting out risks for human cancer is a losing strategy in the war on cancer.

Unless there’s a lot more to ACSH’s book, this is a cartoon depiction of carcinogen policy that scarcely resembles the actual agency approach (recently updated as of March 2005, months after publication of America’s War on “Carcinogens”). A summary of that approach, presented here, emphasizes full characterization of all of the information used to identify substances as carcinogens and characterize their dose-response (not just the animal bioassay data), and an expanded role for mode-of-action data (which responds in part to the ongoing concern that tumors observed in high-dose animal studies cannot be appropriately extrapolated to low-dose human exposure). A range of approaches for extrapolation from high-to-low dose settings are provided, not just the linear non-threshold model first published in the 1986 version of the carcinogen guidelines, and a favored whipping boy for the anti-carcinogenic regulatory crowd. In short, it is possible that ACSH is complaining about a carcinogen risk assessment policy that has been superseded for many years?

Some of the talking points from the book are in a Western Legal Foundation backgrounder produced by ACSH. It strays off topic at times (see for yourself), and today’s post isn’t the place to deconstruct the environmentalist blame-fest for all of humankind’s woes that are in it. Presented below are some of the talking points regarding carcinogen assessment from ACSH’s legal backgrounder; in some cases I’ve provided corresponding statements from EPA’s guidelines for carcinogen risk assessment; in others, some follow up commentary:

ACSH: The regulatory science practiced at the EPA/NTP is deficient and based on closely-held beliefs about high-dose animal testing, rather than upon relevant scientific or epidemiological data, and should be reevaluated and modified to conform to generally accepted scientific principles of risk assessment.

EPA: . . . [E]pidemiologic studies typically evaluate agents under more relevant conditions. When human data of high quality and adequate statistical power are available, they are generally preferable over animal data and should be given greater weight in hazard characterization and dose-response assessment, although both can be used (page 2-3).

ACSH: Rather than relying on a few high-dose rodent tests to label a substance “carcinogenic” (or a “likely carcinogen”), the totality of the data should be considered, including evidence from multiple species and human epidemiology when available.

EPA: Evidence considered includes tumor findings, or lack thereof, in humans and laboratory animals; an agent’s chemical and physical properties; its structure-activity relationships (SARs) as compared with other carcinogenic agents; and studies addressing potential carcinogenic processes and mode(s) of action, either in vivo or in vitro. Data from epidemiologic studies are generally preferred for characterizing human cancer hazard and risk. However, all of the information discussed above could provide valuable insights into the possible mode(s) of action and likelihood of human cancer hazard and risk. The cancer guidelines recognize the growing sophistication of research methods, particularly in their ability to reveal the modes of action of carcinogenic agents at cellular and subcellular levels as well as toxicokinetic processes.

Weighing of the evidence includes addressing not only the likelihood of human carcinogenic effects of the agent but also the conditions under which such effects may be expressed, to the extent that these are revealed in the toxicological and other biologically important features of the agent (page 1-12).

ACSH: This sort of approach is actually what FDA used for substances “grandfathered” at the time of the Delaney Clause, e.g., aflatoxin, a well studied and potent human carcinogen, is allowed to be present in foods at minute levels known to be without risk at those levels.

I guess the point being made here is that FDA has a distinctly different and superior approach to carcinogen risk assessment from EPA. I’m having to dredge up the history of aflatoxin regulation to understand this one better, but I have found a statement by Joseph Roderick from a 2001 conference, reminiscing about his time at FDA when aflatoxins were being addressed, and stating that “EPA has been quite good about guidelines, FDA has not done that, but their assessments are very much like EPA's.” That doesn’t sound so different to me.

ACSH: This same approach should be applied—based on sound science in risk analysis—to all suspected carcinogens, whether synthetic or natural.

EPA: The cancer guidelines cover the assessment of available data. They do not imply that one kind of data or another is prerequisite for regulatory action concerning any agent. It is important that, when evaluating and considering the use of any data, EPA analysts incorporate the basic standards of quality, as defined by the EPA Information Quality Guidelines (U.S. EPA, 2002a see Appendix B) and other Agency guidance on data quality such as the EPA Quality Manual for Environmental Programs (U.S. EPA, 2000e), as well as OMB Guidelines for Ensuring and Maximizing the Quality, Utility, and Integrity of Information Disseminated by Federal Agencies (OMB, 2002). It is very important that all analyses consider the basic standards of quality, including objectivity, utility, and integrity. A summary of the factors and considerations generally used by the Agency when evaluating and considering the use of scientific and technical information is contained in EPA's A Summary of General Assessment Factors for Evaluating the Quality of Scientific and Technical Information (U.S. EPA, 2003) (page 1-5).

It is difficult to imagine that guidelines highly unfavorable to industry could emerge from a regulatory agency under the thumb of the Office of Management and Budget (OMB) in the Bush Administration. There is a lot more to say about this topic (more on it later – this post was already a couple of days in the making), but for now it’s sufficient to say that there’s a distinctly different story to tell about how carcinogens are studied and regulated than the one coming from ACSH.