Chicago, August 16, 1996.— Cancer Prevention Coalition, Chicago
EPA's recent Proposed Guidelines for evaluating cancer risk threaten to roll back the agency's limited regulation of carcinogenic pesticides and industrial chemicals. These proposals trivialize the significance of animal carcinogenicity tests, and require that their results be validated by evidence of similar mechanisms of actions of carcinogens in animals and humans. Further, they place unrealistic emphasis on epidemiology as the major mechanisms for identifying carcinogenic risks.
These and other criticisms are detailed in the attached August 16, 1996 letter to EPA. This letter has been endorsed by 25 leading scientists, and by 50 environmental and public interest groups representing a constituency of some 10 million citizens.
Failure of the cancer establishment to provide EPA with guidance on the scientific invalidity of these proposals is consistent with its track record of indifference to cancer prevention.
August 16, 1996
Technical Information Staff (8623)
U.S. Environmental Protection Agency
401 M Street, S.W.
Washington, D.C. 20460
We express grave concerns over EPA's April 23 proposed Guidelines for evaluating the cancer risk of pesticides and other industrial chemicals. These new guidelines claim to "modernize the science of cancer risk assessment" by: relying on microbiological, genetic and mechanistic "weight of evidence"; prioritizing epidemiological over experimental evidence of carcinogenicity; and downgrading carcinogenic effects induced in animals at "only excessively high doses never seen in the environment" (EPA Press Release).
Furthermore, EPA proposes that these carcinogenic effects be qualified by criteria such as whether the induced tumors are "benign" or malignant and whether or not they metastasize. EPA also proposes that threshold or non-linear dose-response extrapolation "is appropriate when there is no evidence of linearity".
EPA's proposals invite regulatory gridlock. They seek to replace the single criterion of experimental evidence on carcinogenicity by a complex of multiple lines of evidence of arguable merit and relevance, and thus open the Agency's floodgates to interminable special interests challenge. They also seek to shift decision-making away from scientist toward "risk managers". Furthermore, the proposals are scientifically flawed:
There is a consensus in the scientific literature on the validity of qualitative extrapolation of experimental carcinogenicity data to human risk, irrespective of ancillary "weight of evidence". All the 23 recognized human carcinogens are also carcinogenic in experimental animals, and for many of these carcinogens, the animal data preceded epidemiological confirmation (Rall, D., Ann. NYAS, 534:78-83, 1988); for 18/23 of these carcinogens, one or more sites in humans were predicted experimentally.
Carcinogenicity testing is inherently insensitive as: a statistical function of the very small number of animals tested in relation to the many million humans at presumptive risk; the short life span of experimental animals relative to the long duration of human exposure; and the possibility that humans are more sensitive to particular carcinogens than animals. In an attempt to reduce such gross insensitivity, National Toxicology Program bioassays are routinely conducted at maximally tolerated doses (MTD) and MTD/4. For those few carcinogens, dimethylnitrosamine, vinyl chloride and acetylaminofluorene, whose testing has been extended downwards below MTD/4, carcinogenic effects have persisted at the lowest levels tested; contrary to EPA, such levels are "seen in the environment".
The remarkable advances in our understanding of the molecular mechanisms of carcinogenesis over the last few decades are fully consistent with linear dose-response extrapolation. However, in the absence of affirmative evidence of linearity, EPA's Guidelines permit non-linear extrapolation and the establishment of allegedly safe or threshold exposure levels.
EPA's emphasis on the role of mechanistic and genetic data invites special interest challenge to experimental evidence of carcinogenicity. Illustrative is industry's insistence that methylene chloride is not carcinogenic as it allegedly induces cancer in only mice, and not rats or humans, and since it is more actively metabolized via a glutathione pathway in mice than in rats and humans; in fact, methylene chloride is also carcinogenic in rats (IARC, 41:43-85, 1986). Zeneca Pharmaceuticals also urges such downgrading: "We now have an excellent database for that kind of (mechanistic) evaluation". This strategy is also aggressively supported by industry's academic consultants and organizations such as Harvard's Center for Risk Analysis which is seeking to downgrade the carcinogenicity of formaldehyde and chloroform on the basis of "new biological evidence". Similar challenges are also being directed to a wide range of other carcinogens, including nitrilotiracetic acid, EBDC fungicides, ethyl acrylate, and others inducing mouse liver tumors. Finally, it should be stressed that insistence on "mechanistic data" ignores the fact that we still do not know the mechanism of action of any single carcinogen.
EPA's Guidelines are myopically and unrealistically fixated on risk assessment for individual carcinogens, rather than on aggregate risks posed by a multiplicity of industrial carcinogenic contaminants in air, water, food and other consumer products and the workplace,, with multiple routes of exposure.
EPA's emphasis on the "greater weight of human data - (as) generally preferable over animal data", is misplaced and unrealistic. Epidemiological studies are generally unavailable for industrial chemicals in commercial use (Tomatis, L., Ann. NYAS, 535:31-38, 1988). Furthermore, such relatively few studies are commonly confounded by inadequate exposure data, sample size and follow-up, besides other limitations.
EPA Guidelines make no attempt to assess the increased cancer risks of children and pregnant women. "It is understood that - certain sensitive human subpopulations may be left without risk assessments"; this admission is contrary to EPA's Press Release.
Of particular concern, EPA's proposals fail to encourage industry's active participation in risk assessment. For example, industry should be requested to routinely develop microbiological and genetic data as possible early warning signals for the wide range of chemicals in use which are still untested for carcinogenicity. For those carcinogens detected at relatively high dose levels, MTD and MTD/4, industry should be invited to conduct appropriate dose-response tests at levels extending down to environmental levels. Industry should further be invited to conduct valid epidemiological studies, with detailed exposure data, n workers exposed both to chemicals as yet untested for carcinogenicity and to chemicals found to be carcinogenic in routine animal tests.
Scientific and policy considerations apart, the highly technical and complex Guideline narrative effectively precludes participation by the general public and minority communities alike, thus failing to reflect principles of environmental justice. Of related concern is the absence of any reference to scientific and lay representation of citizen, public interest and labor groups in EPA's Scientific Advisory Board
Finally, EPA's proposals would erode its currently limited regulation of carcinogens. They would also result in a further increase of avoidable carcinogenic exposures. At a time of escalating cancer rates, EPA should more appropriately direct its policies to preventing risks of cancer by toxic use reduction strategies, rather than by attempting to manage them.
SUBMITTED AND ENDORSED BY:
- Samuel S. Epstein, M.D., Chairman of the Cancer Prevention Coalition; and Professor of Environmental Medicine, School of Public Health, University of Illinois at Chicago Medical Center
- Barry Castelman, Ph.D., Environmental Consultant, Baltimore
- Eve Clute, Director, Institute of Body Therapeutics, Lihaina Maui, HI
- Dr. Thomas Higginbotham, Colorado Springs, CO
- Susan Ivey, M.D. MHSA, University of California, Berkeley
- Dr. Marvin S. Legator, Professor of Community Health, University of Texas - Galveston Medical Branch
- Dr. Brian Leibovitz, Editor-in-Chief, Journal of Optimal Nutrition, Davis, CA
- Dr. Edward Lichter, Professor of Medicine, University of Illinois - Chicago, Illinois
- Dr. William Lijinksy, Ph.D., Member of the Board of Directors, Cancer Prevention Coalition; and Former Director of Chemical Carcinogenesis Program, Frederick Cancer Research Center, Maryland
- Dr. Thomas Mancuso, Emeritus Professor Occupational Medicine, University of Pittsburgh, PA
- Franklin Mirer, Ph.D., Director Health and Safety, United Auto Workers, MI
- Dr. Vicente Navarro, Professor of Health Policy, John Hopkins University
- Herbert Needleman, M.D., University of Pittsburg Medical Center
- John Olney, Professor of Medicine, Washington University School of Medicine, St. Louis, MO
- Dr. Peter Orris, Division of Occupational Medicine, Cook County Hospital, Chicago
- Michael Plewa, Professor of Genetics, University of Illinois - Champaign
- Kenneth Rosenman M.D., Professor of Medicine, Michigan State University
- Janette Sherman, M.D., Alexandria, VA
- Dr. Sandra Steingraber, Boston, MA
- G. Marie Swanson, Ph.D., M.P.H., Director and Professor of Family
Practice and Medicine, Michigan State University, MI
- Dr. Joel Swartz, Charles Drew Medical University, Los Angeles, CA
- George Wald, Nobel Laureate, Harvard University
- Charles F. Wurster, Emeritus Professor of Environmental Studies, State University of New York
- Dr. Quentin Young, President American Public Health Association, Chicago, Illinois
- Dr. Arthur C. Zahalsky, Professor of Immunology, Immunox, Inc, Edwardsville, IL
- Grace Ziem, M.D., Baltimore, MD
- H. Bishop Dansby Esq., Harrisburg, VA
- Gaylord Nelson, General Counsel , Wilderness Society
- Delores Pino, J.D., Chicago, IL
- Ceil Sinnex, Editor, Gynecologic Cancer Prevention News
- Leonard W. Schroeter, Association of Trial Lawyers of American, Seattle, WA
- Les Reid, Sierra Club, Pine Mountain, CA
- David Steinman, Investigative Reporter, CA
- Martin Teitel, PhD., Executive Director, C.S. Fund, Freestone, CA
- Anthony Mazzocchi, Oil, Chemical and Atomic Workers Union
- Action Now, CA
- Alaska Clean Air Coalition
- American's for a Safe Future, CA
- Arrest the Incinerator Remediation, Lock Haven, PA
- Boston Women's Health Book collective, MA
- Breast Implant Information Exchange, CA
- Center for Constitutional Rights
- Center for Media and Democracy, Madison
- Chesapeake Bay Foundation, MD
- Chicago Recycling Coalition, IL
- Christian Women Against Cancer, MD
- Citizen Action, DC
- Citizens Against Cancer, MI
- Citizens for Alternatives to Chemical Contamination, MI
- Citizens for a Better Environment, IL
- Coalition for Consumer Rights, IL
- Cold Mountain, Cold Rivers, MT
- Communities for a Better Environment, CA
- Compost Patch Inc.
- Conscious Choice Magazine
- Defenders of Wildlife
- Earthsave International, CA
- Edmonds Institute, WA
- Environmental Action Foundation, MD
- Environmental Health Coalition, CA
- Environmental Health Watch, OH
- Environmental Research Foundation, MD
- Enviro-Health Concerns, KS
- Exeter Citizens for Clean Air
- Farmer - Consumer Alliance, VA
- Feminists for a Compassionate Society, TX
- Food and Water, VT
- Foundation on Economic Trends, DC
- Good Neighbor Project for Sustainable Industries, MA
- Grassroots Coalition for Environmental and Economic Justice, MD
- Grassroots Environmental Organization, NJ
- Illinois Pesticide Education Network
- Illinois Stewardship Alliance
- Institute for Agriculture and Trade Policy
- International Alliance for Sustainable Agriculture, MN
- International Center for Technology Assessment, DC
- Lake Superior Greens
- Legal Environmental Assistance Foundation, AL, FL & GA
- Massachusetts Campaign to Clean Up Hazardous Waste, MA
- Missouri Coalition for the Environment
- Montana Coalition for Health, Environmental and Economic Rights
- Montana Environmental Information Center
- National Hispanic Leadership Institute on Cancer, CA
- National Women's Health Network, DC
- New York City Green Party
- New York Coalition for Alternatives to Pesticides
- New York Environmental Law Project
- Northwest Coalition for Alternatives to Pesticides, OR
- North Carolina Fair Share
- Nutrition for Optimal Health Association, Chicago
- Oil, Chemical and Atomic Workers Union, CO
- Parents Community Council
- Peace Farm, TX
- Pennsylvania Environmental Network
- People Against Cancer, IA
- People for Community Recovery, IL
- Pesticide Action Network North America, CA
- Philadelphia Occupation Safety and health Group, PA
- Pittsburgh Against Toxic Incineration
- Project Impact Inc.
- Pure Food Campaign
- Rachel Carson Trust
- Radiation and Public Health Project, NY
- Safer Pest Control Project, IL
- Southeast Alliance for Environmental Justice, CA
- Southeast Environmental Task Force, IL
- Sierra Club - Lone Star Chapter, TX
- Toxic Links Coalition, CA
- Tri-State Environmental Council
- United Auto Workers, MI
- Victims of Fiberglass
- Women's Cancer Resource Center, CA
- Women's Cancer Resource Center, MN
- Women's Environmental Development Organization, NY
- Women Care, CA
- Women's Community Cancer Project, Boston