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Chasing A Receding Zero: Impact of the Zero Threshold Concept on Actions of Regulatory Officials

Department of Biophysics and Medical Physics and Department of Nutritional Sciences University of California, Berkeley

The principle of toxicological threshold was stated in 1564 by Paracelsus as "All things are poisonous, yet nothing is poisonous. Dosage alone determines poisoning." This principle remains valid, even with consideration of today's public concern with low-dosage effects of compounds that are categorized as carcinogens, mutagens and teratogens. Modern laboratory methods enable detection of increasingly small traces of such compounds in foods. The search for these has been termed "Chasing a receding zero, " and this quest has been stimulated by statements that no one knows how small an amount of a carcinogen, taken for how short a time, can induce cancer, and that even one molecule of a carcinogen, acting on a single cell, can transform a normal cell into a cancer cell.

This latter proposal is a stochastic impossibility. Every cell contains millions of carcinogenic molecules. Examples are arsenic, cadmium and chromium. In addition, there are estrogens and other steroid hormones present in each cell and needed for normal bodily functions. These substances are regarded as carcinogens because of their effect at high levels on increasing the cancer rate in experimental animals. Obviously, there must be a threshold for this effect. An estimate has been made by Dingman that "a threshold for biological activity exists within a cell at 10, 000 atoms."

It is also obvious that there is a threshold for deficiencies that induce cancer, such as that of iodine. Iodine deficiency is mimicked by administration of goitrogens, and these are present naturally at low to moderate levels in many common foods.

The threshold principle is stated by Claus and Bolander to be a law of nature, valid in many circumstances, and governing the fact that a causative agent must be present in a quantity exceeding a definite minimum in order to produce the effect.

International Journal of Toxicology, Vol. 2, No. 3, 147-160 (1983)
DOI: 10.3109/10915818309140698


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