Growth-Inhibition Produced in Rats by the Oral Administration of Sodium Benzoate

Growth inhibition in rats has been produced by the incorporation of a variety of toxic compounds into the diet.2" 22, 23, Further, it has been possible to demonstrate that stimulation of growth occurs under these experimental conditions when one of the sulfur-containing amino acids, cysteine, cystine, or methionine, is superimposed on the basal diet still containing the growth-inhibitory compound. Under these conditions the animals resume growth at a rate comparable to that observed on the basal diet alone. In addition, other substances, e.g., glutathione and cystine disulfoxide, which are known to stimulate growth in rats stunted by one of the so-called "cystinedeficient" diets, have also been shown to be effective growth stimulators when added to the basal, growth-inhibiting diets. Inasmuch as these growth-promoting dietary supplements exert their action when injected subcutaneously, as well as following oral administration, it has been concluded that their effect is a true metabolic one and not due to a reaction occurring in the intestine prior to absorption. The specific and unique capacity of the sulfur-containing amino acids, and of substances behaving in nutrition experiments in a manner similar to these amino acids, to stimulate the growth of animals ingesting a growth-inhibitory basal diet has led to the suggestion that the inhibition of the growth of the rat by certain organic compounds "is a manifestation of the production of a specific deficiency in the sulfur-containing amino acids, probably by imposing on the organism an increased requirement for organic sulfur, in the form of cystine or methionine, for detoxication mechanisms."' However, although direct proof for the formation of a detoxication product (mercapturic acid) is clearly established for the monohalogen benzenes, and