Dioxin And Cancer

An independent scientific panel has begun scrutinizing the Environmental Protection Agency’s most recent draft document that analyzes the cancer risk of the most toxic form of dioxin. At a recent meeting, a majority of the panel’s members indicated that the agency provided sufficient justification for using a risk estimate that might lead to pollution regulations that are stricter than health risks warrant. However, panelists also said EPA needs to consider that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) may not cause cancer at low exposures such as the amounts widely found in the environment.

In the draft document released in May, EPA determined that TCDD poses a cancer risk to humans at any dose (C&EN, May 31, page 41). Scientific controversy swirls around this conclusion, which could have enormous health and financial implications (C&EN, July 12, page 26).

Industrial and federal polluters are pushing hard for EPA to abandon the unsafe-at-any-dose risk estimate. Instead, chlorine chemical producers, pulp- and papermakers, and the military want the agency to conclude that TCDD does not cause cancer at very low doses. Such a decision would likely lead to less extensive and less expensive cleanup of areas contaminated with TCDD or several of its chemical cousins that exhibit similar toxic effects. These related chemicals are other polychlorinated dibenzodioxins, polychlorinated dibenzofurans, and polychlorinated biphenyls (PCBs).

At issue in the draft is the method EPA uses to estimate the cancer risk from TCDD. In a 2003 draft reassessment of the chemical, the agency used a linear model that assumes that risk rises in direct proportion to exposure and that no dose is safe. In addition to cancer, the substance is linked to other adverse health effects such as reproductive and immune-system problems.

At the behest of the George W. Bush Administration, the National Academy of Sciences reviewed the agency’s 2003 draft. The resulting 2006 NAS report recommended that the agency make additional calculations using a model postulating that below some threshold of exposure, TCDD doesn’t pose a cancer risk. The May draft is EPA’s response to the NAS report.

To address the NAS recommendation, the agency said it considered a threshold model but concluded there isn’t enough scientific evidence either to support its use or to rule out the linear one for estimating TCDD’s cancer risks. The task of reviewing the agency’s draft falls to the EPA Science Advisory Board’s Dioxin Review Panel, which will work this summer and fall on determining if the agency’s draft is scientifically acceptable.

At a July 13–15 meeting in Washington, D.C., many of the panel’s 19 members generally agreed there is a growing body of evidence to support the threshold model for TCDD. But, they added, data are not currently sufficient for EPA to reject the linear model and rely solely on the threshold one for assessing the chemical’s cancer risks.

“The evidence is not strong enough to go one way or the other,” summed up panelist Mitchell J. Small, professor of environmental engineering at Carnegie Mellon University.

A large portion of the scientific community believes that TCDD is carcinogenic only at higher doses, according to panel member Harvey Clewell, director of the Center for Human-Health Assessment at the Hamner Institutes for Health Sciences, a nonprofit research organization. There is abundant evidence that this hypothesis is reasonable, he continued.

Yet in the draft response, EPA scientists opted for the linear model because that’s what the agency’s Guidelines for Carcinogen Risk Assessment, adopted in 2005, led them to use, Clewell said. Several panelists indicated they agreed that EPA hewed to its own guidelines.

But some advisers took exception.

Use of the linear model means EPA may be estimating risk for a nonexistent health effect: cancer caused by very low exposures to TCDD, said panelist Karl K. Rozman, professor of pharmacology, toxicology, and therapeutics at the University of Kansas Medical Center. At best, he argued, there is equivocal evidence for TCDD being a carcinogen at exposures found in the environment, in the range of roughly 7 to 10 ppt. Thus, EPA should not conclude TCDD is carcinogenic at any dose until there are conclusive data, he contended.

Rozman said that it appeared to him that the choice of the linear model was an agency policy decision and that science was marshaled to support it. “EPA did adhere to its guidelines” for carcinogen risk assessment, he commented. “That doesn’t mean that [the agency’s decision] is science.”

Likewise, panelist Louis Anthony (Tony) Cox Jr. said EPA’s explanation in the draft of why it chose the linear model “comes across as an argument rather than a pure quest for truth.” He is president of Cox Associates, a Denver consulting company.

As the panel began its deliberations, members heard presentations from representatives of environmental groups and industry. Among them was epidemiologist Devra L. Davis, who urged EPA to finalize its risk assessment while continuing to address TCDD science issues, including those pitting the linear model against the threshold one. EPA could establish a blog on dioxin to allow the public to alert the agency to new scientific evidence about TCDD, suggested Davis, founder of the Environmental Health Trust, a nonprofit that provides education about controllable environmental health risks.

In addition to presenting scientific arguments in favor of the threshold model at the July meeting, industry representatives asked the review panel to scrutinize the calculations EPA uses to compare the hazards of various dioxins, furans, and PCBs. These are called toxicity equivalency factors. Regulators use them in deciding how much cleanup is required at polluted sites. TCDD is given a value of one, and related compounds are each assigned a fraction, based on their individual toxicity. Representatives of Dow Chemical and General Electric, two companies that face massive cleanups, told the review panel that, on the basis of new scientific data, some of these factors for chemicals related to TCDD need to be lowered. Such a move would reduce cleanup liability for those substances.

But Peter W. Preuss, director of EPA’s National Center for Environmental Assessment, asked the panel not to delve into toxicity equivalency factors. The agency is revisiting these conversions in a document separate from its response to NAS, Preuss said. EPA’s Risk Assessment Forum, composed of agency senior scientists, is finalizing a guidance document on TCDD toxicity equivalency factors, he said.

Preuss implored the independent reviewers to limit their recommendations to EPA’s draft response to NAS. He pointed out that the agency has been trying to update its current risk assessment of TCDD, which dates to 1984, for two decades.

“I’m asking that you not give us a report which will require another five years of work and another peer review and continue this process ad infinitum,” Preuss told the advisory panel.

“There are lots of issues awaiting the outcome of this assessment,” Preuss said. But, he added, there is also pressure on the agency from polluters to not finish the analysis so that decisions on regulations and cleanup are left hanging.

The panel will meet again in the fall to assemble its critiques into a report, which is expected later this year.