The Zero-Tolerance Concept

THE ZERO-TOLERANCE CONCEPT GEORGE B. KOELLE* In a memorable scene from Samuel Butler's The Way ofAll Flesh, old George Pontifex drops and breaks a pint bottle ofJordan water that he has been saving for many years for his first grandson's christening. The quick-thinking butler averts an impending crisis (he has been blamed for having misplaced the hamper that Pontifex has tripped over) by snatching up a sponge, recovering halfthe treasured liquid from the floor, and filtering it through a bit of blotting paper. On reflection, the same purpose would have been served by the simpler expedient of turning an adjacent tap and drawing a fresh pint from the local English water supply. It has been calculated that the Jordan daily pours 6.5 x 10e tons of water into the Dead Sea [I]. Thus, when a single day's effluent has equilibrated with the remaining water of the world (which over the course of a few million years it undoubtedly would), estimated as 3.3 x IO8 cu mi [2] or 1.5 x 1018 tons, a pint of water sampled from any source will contain 3.7 X 1012 molecules ofJordan water. To extend this concept still further, if a pint of water is poured into the sea and allowed to mix completely with all the water on the surface of the earth, over 5,000 molecules of the original sample will be present in any pint taken subsequently. The general conclusion to be drawn from these calculations is that nothing is completely uncontaminated by anything else. Yet this conclusion is in conflict with both the implications and applications of certain items of federal legislation that have led to serious limitations in the production of foods and drugs. The best known and most controversial of these is the Delaney Amendment to the Food Additives Amendment of 1958, sec. 409 (c) (3) (A) ofthe Federal Food, Drug, and Cosmetic Act. Paraphrased, the amendment states simply that no additive found to induce cancer in any animal species following oral ingestion shall be deemed safe. On first consideration, this seems quite reasonable. However , as was brought out in extensive hearings before a subcommittee of the Committee on Appropriations of the House of Representatives in May 1974 [3], its interpretation and enforcement have followed lines¦"Department of Pharmacology, Medical School, University of Pennsylvania, Philadelphia , Pennsylvania 19174. Perspectives in Biology and Medicine ¦ Summer 1977 | 507 that seem to have ignored both the well-established pharmacological principle of "threshold dose" (that below which no effect is detectable) and the remarkable degrees of improvement in the sensitivity and specificity of analytical methods that have now been developed. Thus, the enforcement agency has labeled as unsafe any compound that can be demonstrated to cause a higher incidence than in controls of any type of cancer in any species when added to the diet in any concentration for any period of time. By extrapolation from the test animals to human subjects, it has been estimated that the latter would have to consume up to 500 12-oz bottles of soft drink daily to achieve a carcinogenic dose of cyclamate. For oil of calamus, which has been used as a constituent of vermouth, the extrapolation is truly staggering; attainment of a carcinogenic level would require the daily consumption of 250 qt of vermouth , which in a standard ratio of 1 part to 9 parts of gin represents over 50,000 1.5-oz martinis. Yet despite such figures, these compounds and others have been proscribed as additives. In the former case, the consumer has the choice to weigh the great or small hazard of consuming an equivalent amount of sugar or of some other synthetic substitute ofyet unproven carcinogenic potential against his desire for soft drinks; in both cases, the manufacturer may no longer include the condemned compound in his product. No such simple solutions are afforded by a more recent proposal issued by the Food and Drug Administration in April 1976 [4]. This relates to the finding that when male rats were given chloroform in a dose of 90 or 180 mg per kilogram orally five times weekly for 78 weeks, significant numbers (8...