2006 Naphthalene State-of-the-Science Symposium

Home

Program & Agenda
• Event Schedule
• Planning Committee

Invited Participants

Reference Material

Registration

Travel and Accommodations

Sponsors

Co-Sponsors

Society for Risk Analysis

What is naphthalene, how is it used, and how are people exposed?

Naphthalene is a bicyclic aromatic hydrocarbon with the chemical formula C10H8. Pure naphthalene is a white, water-insoluble solid at room temperature. It is produced by distillation and fractionation of either petroleum or coal tar. Naphthalene's principal use is as an intermediate in the production of phthalic anhydride, a chemical important in the manufacture of phthalate plasticizers, resins, dyes, and insect and animal repellents. Naphthalene is also used in the manufacture of synthetic leather tanning agents and the insecticide carbaryl. Naphthalene has been used as a moth repellent and as a deodorizer for diaper pails and toilets. A large number of hazardous waste sites included on the U.S. Environmental Protection Agency's (U.S. EPA's) National Priorities List have detectable levels of naphthalene that heretofore have not been believed to pose any appreciable risk to human health. Naphthalene exposure is widespread in the environment at part per billion (ppb) levels.

Does naphthalene cause cancer in humans?

Historically, naphthalene in the environment has been believed to present no material human cancer risk. This view was based on the fact that ambient environmental levels are in the ppb range, and there have been no credible scientific studies showing that naphthalene caused cancer in animals even at doses more than a thousand times greater. In 2001, however, the U.S. National Toxicology Program (NTP) released the results of a two-year bioassay showing that some rats exposed to doses of 10, 30 and 60 parts per million (ppm) exhibited rare cancers in the nasal epithelium. Based on this study, U.S. EPA's National Air Toxics Assessment extrapolates that as much as 5% of all cancers from air toxics are attributable to naphthalene.

Why is science important?

The protection of public health is our primary concern. If naphthalene at environmental concentrations does cause cancer in humans at the rate implied by the various risk factors that have been proposed based on this NTP study, then thousands more Americans experience cancer over their lifetimes than if these exposures were prevented. On the other hand, if naphthalene at environmental doses causes cancer in humans at less than these implied rates (or perhaps not at all), then resources expended to avoid human exposure will not reduce the number of persons who experience cancer, but they will diminish national and individual wealth, including the capacity to invest in other goods, services, and activities that reduce or eliminate cancer and other human health risks.

What is NS³ about?

Our goal is first to provide a circumspect accounting of what is known and unknown about fundamental scientific issues related to the human carcinogenic risk posed by exposure to naphthalene at environmentally relevant doses. Second, we seek to provide an independently validated agenda for research having a high level of policy-relevant information value.

Specifically, NS³ is designed to:

Share openly, with participation invited from all interested parties, all salient knowledge regarding the specific scientific issues that will be addressed, with formal presentations by leading investigators;

Report the collective scientific wisdom of a panel of independently-selected and universally-recognized scientific experts; and

Propose an agenda for research that if conducted, will resolve critical remaining scientific uncertainties.

Apply uncertainty analysis methods to those scientific areas that cannot be adequately resolved by the conduct of timely, cost-effective research.

NS³ will therefore provide valuable information to basic research scientists, applied scientists and risk assessors, public- and private-sector research sponsors, risk managers, and advocates of all persuasions who are committed to public policies informed by science. Since January 2006 when we first wrote to you, we have expanded both the NS³ Planning Committee to achieve even greater diversity and broadened the scope of the event to explicitly address uncertainty analysis. These changes ensure that NS³ will be a cutting-edge event.

NS³ will review four fundamental science issues related to the quantification of human cancer risk from naphthalene exposure at environmentally relevant levels. Researchers who performed the most important recent scientific studies in animal systems on metabolism, biochemistry, animal-to-human extrapolation, and mechanism of action will present their work. A review of the literature on human exposure, occupational and environmental epidemiology, and the incidence in humans of nasal epithelial tumors (the specific tumors reported in the NTP bioassay) also will be presented.

The audience for NS³ is scientists, consultants, industry, advocacy groups, regulatory agency officials, and others interested in learning the latest about naphthalene first-hand from scientists who have performed and published the most relevant scientific research. We are bringing together distinguished, independent scientists who will provide their informed insights on these subjects and help craft consensus reports on the state of the science. Our expert panels will identify gaps in scientific knowledge and help craft specific, targeted, cost-effective research projects that could be performed in a timely manner which would resolve many remaining scientific uncertainties. Some scientific uncertainties are impervious to resolution by scientific means, or they cannot be resolved promptly or cost-effectively. For these matters NS³ explicitly includes a day devoted to the framing (and if possible) application of appropriate uncertainty analysis tools.

Our goals are twofold: first, to produce a research agenda that, if promptly and cost-effectively implemented, would enable human health risk assessment and risk management to be informed by the best available science; and second, to expedite the completion of a scientifically-based assessment of human cancer risk at environmentally relevant doses that captures scientific uncertainty. The four fundamental science issues to be addressed by NS³ are:

Animal data. The most important laboratory study on naphthalene was performed by the NTP and published in 2001. What was the basis for its design? How was it performed? What did it reveal? What inferences are scientifically appropriate to make from it?
Human data. What is known about human exposure to naphthalene, especially in environmental contexts? What does the body of occupational and environmental epidemiology tell us? What is the incidence in humans of the specific types of cancer observed in the NTP study?
Anatomy, Physiology, and Metabolic Activation and Deactivation. The primary mode of action is cytochrome P-450 metabolism in tissues at or near the point of contact in the respiratory system. Most data have been obtained from animal models. What is known (and unknown) about naphthalene metabolites? How much metabolism occurs, and under what conditions? To what extent can the production of metabolites be related to their carcinogenic potential? What are the relevant similarities and differences between animals and humans? What do we know (and don't know) about developmental and gender differences in animals? To what extent can these differences be quantified?
Mechanisms of carcinogenesis. Alternative mechanisms of carcinogenesis have been suggested, including both genotoxicity and cytotoxicity. What data exist that support or contradict each of these alternative mechanisms? Do they operate at differential intensities at different doses? To what extent can carcinogenic potential be quantified?

For each module a pool of recognized experts has been assembled by the Planning Committee from which all expert panelists will be drawn. Each individual listed is widely respected for intellectual rigor, scholarship, independence and open-mindedness, and was identified by consensus. The identities and affiliations of members of the Planning Committee are listed in Attachment A.

Attachment B provides an outline of the NS³ program, including the scientific topics to be addressed, the identities and affiliations of the invited research speakers, and the names and affiliations of members of the expert panel pool. At this time we are unaware of any conflict-of-interest concerns that would cast doubt on the ability of any scientist on this list to capably and fully perform the duties assigned.

What is NS³ not about?

NS³ is not about policy. Our focus is strictly on science, and in particular, primary scientific data, opportunities for scientific research, and the application of uncertainty analysis where research is technically infeasible or cannot be performed promptly or cost-effectively. For that reason, NS³ will not review the adequacy or sufficiency of risk assessment documents prepared by various government agencies or private stakeholders, nor will we debate the merits of public policy judgments that are (or could be) contained in such risk assessments. That is, NS³ will not take sides on policy issues. The purpose of NS³ is to inform the policy debate with science, not to debate what policy choices ought to be made.

What is the symposium format?

Each scientific issue will be addressed by scientists who have performed primary research and published extensively on the subject. Research speakers were selected based on their relevant primary scientific research. They will present and summarize the data they have collected and explain what inferences they think ought to be drawn from their work.

For each scientific modules, a panel of recognized independent experts will review the data and develop consensus reports on the state of the science. They will also identify gaps in scientific knowledge that currently give rise to the use of default assumptions in human health risk assessment and propose specific, targeted, cost-effective research projects that would, if performed, resolve these scientific uncertainties. Research speakers, who are likely to be most familiar with the existing data and have well developed ideas concerning areas of promising future research, will be encouraged to suggest research ideas for consideration by these panels. The goal is to obtain a broad-based scientific consensus on a research agenda that is financially feasible; that can be accomplished without delay; that will enable risk assessment and risk management to be maximally informed by science; and that will expedite the completion of a scientifically-based human health risk assessment informed by uncertainty analysis.

Expert panelists will deliver preliminary reports on their deliberations at the end of the Symposium. Within a short period thereafter, they will complete written reviews suitable for publication in an appropriate scholarly journal.

Unlike some scientific workshops, NS³ will be highly interactive. There will be extensive opportunity for public participation-in fact, there will be an hour allotted to question-and-answer time for each hour of scientific presentations delivered by research speakers. At the same time, because NS³ will be strictly scientific, policy matters (such as how much public health protection is appropriate or how precautionary risk managers ought to be) will be strictly excluded from the discussion.