ANS National
 Meetings/
 Sessions

June 1995

Ralph R. Cook

(Dow Corning)

2. An Alternative Viewpoint to the Biological Effects of Low-Level Exposures

                “Perceptionis culturally determined. Everyone, including scientists and engineers, are conditioned to particular mental constructs. These ‘bits of themind’ or paradigms both facilitate and constrain our ability to interpretdata.^1-3 As one consequence, the biological effects of low-level exposures to toxic chemicals and radiation are presumed to be analogous to, albeit possibly of lesser magnitude than, those associated with high level exposures. There is a growing body of evidence that suggests that assumption is incorrect.

                “Operatingunder the acronym BELLE (biologic effects of low-level exposures), a group of government, academic, and private sector scientists are exploring alternatives to the traditional linear, no-threshold, dose-response model. To date, their primary efforts have been educational. Through the distribution of the BELLE newsletter, presentations at scientific meetings, and the publication of symposia proceedings, they are encouraging their peers to collect and evaluate data using non-traditional paradigms.

                “Thispaper explores the concepts of paradigms in general and scientific paradigms in particular. It also addresses the process of paradigm shifts. Through a series of data-based examples, it challenges the assumptions inherent to the current toxics model and offers three alternatives: nonlinear dose response in which the effects seen at low levels may be interpreted as paradoxical or even beneficial, a holistic model in which the outcome of interest is the whole animal and not a specific organ or biological process, and a trade-off model in which the unit of study is the population and not the individual.

                “Examplesare drawn from the epidemiology and clinical literature, and the results of invitro and in vive experimental studies are used in support of the observational research, in particular to provide an understanding of possible underlying mechanisms. Specific examples include vitamins and essential elements, medications such as aspirin and thalidomide, alcohol, toxic chemicals such as2,3,7,8-tetrachloro-dibenzo-p-dioxin (so-called ‘deadly dioxin’), and radiation.^4-12

                “Whilethe current database is provocative when interpreted in a non-conventional manner, the BELLE initiative is constrained because it must utilize data that have been collected, evaluated, and presented in the traditional mode. More resources must be directed toward the development of research projects specifically designed to test the assumptions inherent to the alternative hypotheses.

                “Thecurrent approach to toxics is often presented as conservative, as an error on the side of safety. It is nonetheless an error and one that likely is associated with inadvertent adverse results.”

1. J. L. CASTI, Paradigms Lost- Tackling the Unanswered Mysteries of Modern Science, Avon Books, New York (1989).

2. T. S. KUHN, The Structure of Scientific Revolutions, 2nd ed., The University of Chicago Press, Chicago, Illinois (1970).

3. H. MARGOLIS, Paradigms and Barriers -How Habits of the Mind Govern Scientific Beliefs, The University of Chicago Press, Chicago, Illinois (1993).

4. A. H. SMITH, K. D. WALLER, "Serum Beta-Carotene in Persons with Cancer and Their Immediate Families," Am. J. Epidemiology, 133, 661(1991).

5. L. C. CLARK, "The Epidemiology of Selenium and Cancer," Federation Proc. 44, 2584 (1985).

6. J. E. BURING, C. H. HENNEKENS, "Prevention of Cardiovascular Disease: Risks and Benefits of Aspirin," J. Gen. Internal Med., 5 (Suppl. 5), S54 (1990).

7. E. SCHIFF, E. PELEG, M. GOLDENBERG, T. ROSENTHAL, E. RUPPIN, M. TAMARKIN, G. BARKAI, G.         BEN-BARUCH, I. YAHAL,  J. BLANKSTEIN, B. GOLDMAN, S. MASHIACH, "The Use of Aspirin to Prevent Pregnancy-Induced Hypertension and Lower the Ratio of Thromboxane A2 to Prostacyclin in Relatively High Risk Pregnancies," New England J. Med.,321, 351 (1989).  

8. T. RANDALL, "Thalidomide's Back in the News But in More Favorable Circumstances," J. Am. Med. Assoc., 263,1467 (1990).

9. A. L. KLATSKY, M. A. ARMSTRONG, G. D. FRIEDMAN, "Alcohol and Mortality," Ann. Internal Med., 117, 646(1992).

10. R. J. KOCIBA, D. G. KEYES, J. E. BEYER, R. M. CARREON, C. E. WADE, D. A. DITTENBER, R. P. KALNINS, L. E. FRAUSON, C. N. PARK, S. D. BARNARD, R. A. HUMMEL, C. G. HUMISTON, "Results of a Two- Year Chronic Toxicity and Oncogenicity Study of2,3,7,8-tetrachlorodibenzo-p-dioxin in Rats," Toxicol. Appl. Pharmacol.,46, 279 (1978).

11. J. F. GIERTHY, D. W. LINCOLN, "Inhibition of Postconfluent Focus Production in Cultures of MCF-7 Human Breast Cancer Cells by 2,3,7,8-tetrachlorodibenzo-p-dioxin," Breast Cancer Rsrch. Treatment, 12, 227 (1988). 

12. R. A. BERTAZZI, C. AOCCHETTI, A. C. PESATORI, S. GUERCILENA, M. SANARICO, L. RADICE, "Ten-Year Mortality Study of the Population Involved in the Seveso Incident in 1976," Am.  J. Epidemiol, 129, 1187, (1989)