On the Safety of Estrogenic Hormone Residues in Edible Animal Products

Abstract

The Delaney clause or amendment (1969) of the Federal Food, Drug, and Cosmetic Act states, in essence, that if carcinogenic substances are used as feed additives no residues determined methods of examination prescribed or approved by the Secretary are allowable in edible products for human use. Everyone agrees that consumers should be protected from the involuntary ingestion of amounts of residues which might produce cancer. Involuntary is a key word because patients voluntarily may use prescribed estrogens, known to be carcinogens or cocarcinogens at high dosage levels as, for example, the use of the postcoital pill to prevent implantation of the conceptus (Morris and van Wagenen 1973). With many so-called chemical carcinogens such as 7-12-dimethylbenz [a] anthracene (DMBA), some of which are mutagenic (Miihlbock and Boot 1958, Hollaender 1971), no safe levels have been established. The situation with essential nutrients and natural hormones used as feed additives, which have been labeled as carcinogens or cocarcinogens, differs, however, in that these substances are normal body constituents and perform useful physiological functions. Means of preventing the involuntary consumption of harmful amounts of hormonal residues in edible animal products is our concern in this paper. In short, we are suggesting that low levels of residues of essential nutrients or of natural or synthetic hormones are noncarcinogenic and thus, that these low levels are not subject to the Delaney amendment. The problem, therefore, is in defining levels of residues of hormones in animal products which involve no risk to people consuming these food products. Distinctions between the so-called chemical carcinogens and hormones have been drawn by Miihlbock and Boot (1958): It is not possible to induce cancer with a single large hormone dose nor is the tumor-exciting effect of hormones irreversible before tumor formation actually occurs. The conclusion must be that other mechanisms are instrumental in the hormonal induction of cancer as compared with the so-called chemical carcinogens. On the basis of studies of mouse mammary cancer, Bern (1960) suggests, (1) hormonal factors involved in the evolution of a definite precancerous state may be no more than those factors in normal tissue development; (2) the tumorigenic role of the hormonal milieu may be no more than the continued maintenance of a degree of hyperplasia (the precancerous state); (3) the so-called tumorigenic hormone may be but one component of an essential milieu wherein no one hormone can be considered more essential than any other; (4) in general, the hormonal influence may be a 'permissive' one, essential for tumor appearance but not itself inductive. Gardner (1939) reviewed studies indicating that sufficiently large amounts of all natural estrogens tested would increase the incidence of mammary cancer in mice and synthetic estrogens were soon found to act similarly (Shimkin and Grady 1941). In all instances known to us, hormones are carcinogenic only when given in amounts greater than the amounts required to produce a physiological