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Introduction Although vitamins are essential in the diet for normal health, they may have adverse physiological effects when consumed in excessive amounts. Vitamin intake levels that are above those required to prevent specific deficiency syndromes but still below levels shown to produce toxicity can be said to be tolerated. In this sense, tolerance indicates the absence of deleterious ef- fects of vitamin intakes above those needed to prevent nutritional deficiency disorders. Understanding of the range of tolerance for each vitamin is important in the safe and adequate feeding of domestic and laboratory animals. To ensure optimal animal health, vitamin in- takes must be maintained within these ranges, whether those intakes are through the use of vitamin supple- ments to animal feeds or vitamins in enteral prepara- tions. The term vitamin is generally accepted to describe an organic compound that is (1) a component of a natural food, but is distinct from carbohydrate, fat, protein, and water; (2) present in most foods in minute amounts; (3) essential for normal metabolism in animals and conse- quently required for normal health and physiological functions such as growth, development, maintenance, and reproduction; (4) a cause of a specific deficiency disease or syndrome if absent from the diet or improp- erly absorbed or utilized; and (5) unable to be synthe- sized by the host in sufficient amounts to meet physiological demands and therefore must be obtained from the diet. Most of the traditional vitamins, such as the vitamins A, E, K, B6, and Bit, thiamin, riboflavin, folic acid, pantothenic acid, and biotin, satisfy each of these criteria. Vitamins C and D, niacin, and choline, however, are considered vitamins only in certain contexts. For exam- ple, ascorbic acid is produced metabolically by most species from glucose via the uronic acid pathway. Only the few species that lack the enzyme ~-gulonolactone oxidase (for example fishes, the guinea pig, the Indian fruit bat, the red-vented bulbul, and higher primates) require preformed ascorbic acid in the diet. For them, ascorbic acid is vitamin C. Vitamin D, while biosynthe- sized by animals upon exposure to the ultraviolet radia- tions in sunlight, is also a vitamin in the context of the environmentally controlled housing (and the associated use of artificial lighting) commonly used in modern sys- tems of confined rearing of animals. Niacin is produced metabolically from the indispensible amino acid tryp- tophan. Nevertheless, the efficiency of this conversion is low enough that most animals (especially cats, fishes, and ducks) fed the tryptophan levels typical of mixed practical diets also need a dietary source of niacin. Cho- line, which is produced metabolically from the amina- tion and subsequent methylation of serine, appears not to be biosynthesized in sufficient amounts to satisfy the metabolic demands of rapidly growing chicks and poults. In the context of young poultry, therefore, cho- line is a vitamin. To summarize, compounds that satisfy the definition of a vitamin noted above are traditionally considered vitamins and are examined in this report. As pointed out above, the concept of vitamin toler- ance indicates exposure to vitamin levels that prevent deficiency diseases but produce no signs of intoxication. Thus, it must be the goal of the animal producer, feed manufacturer, and veterinarian to provide vitamins to animals at levels that are sufficient to prevent vitamin deficiency disease and that can be well tolerated. To ensure vitamin tolerance in animal production, there is the practical need to define maximum tolerable levels. The current scientific literature, however, is not com- plete enough to support the estimation of maximum tol- erable levels for any vitamin. In most cases, however, one can use the literature to estimate ranges of vitamin intake that can be presumed to be safe. For the purposes of this report, these upper levels of vitamin intake are 1

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2 Introduction called presumed upper safe levels. It is reasonably clear that these levels will not impair any aspect of animal health or production efficiency and will not accumulate as hazardous residues in human food products derived from animals. Presumed upper safe levels for specific vitamins, therefore, will be less than maximum tolera- ble levels. The presumed upper safe level for each vita- min will vary according to the chemical form of the vitamin; the route of administration, for example, oral versus parenteral; the length of exposure, for example, acute versus chronic; and the particular species and de- velopmental state of the animal, according to such species-dependent variables as degree of endogenous synthesis and efficiencies of absorption, retention, and tissue storage. In order to identify presumed upper safe levels of each of the traditional vitamins, the pertinent scientific litera- ture is presented, and the major findings are discussed. In a few cases, the presumed upper safe levels for cer- tain vitamins with certain species are identified through a straightforward review of published information. In most cases, however, the current scientific literature is not complete enough to indicate these levels unequivo- cally. For these vitamins, presumed upper safe levels are estimated by extrapolation and inference from the available data. The focus of this report is on vitamin intake by domestic and laboratory animal species with emphasis on dietary exposure. Where information from studies with humans is enlightening, it has been in- cluded in considerations of vitamin tolerance of animals. When planning animal diets, it is good practice to consider factors such as vitamin bioavailability and sta- bility during storage and animal physical and metabolic stresses. These factors can influence the levels of vita- mins and other nutrients that animals require. Thus, vitamin levels used in practical animal feeding are ex- pected to be greater than those traditionally recognized as the nutritional requirements. The use of such "mar- gins of safety," however, carries with it risks of vitamin toxicity. In an attempt to help minimize risk, the pre- sumed upper safe levels of vitamins have been identi- fied in this report.