effects upon serum thyroxine and triiodothyronine concentrations have been studied in rhesus monkeys (Mehta et al., 1986), and chronic cadmium poisoning has been induced in cynomolgus monkeys as a model of human itai-itai disease (Umemura, 2000). The publication MineralTolerances of Domestic Animals (National Research Council, 1980) provides information on the toxicity of specific minerals in diets for farm animals, pets, and some laboratory animals.
Interactions of minerals with each other and with other nutrients have been fairly well studied in laboratory and domesticated animals (Underwood, 1981; Mertz et al., 1986, 1987; National Research Council, 1995). For example, in rats, calcium absorption decreases in the presence of high dietary phosphorus (Schoenmakers et al., 1989); this relationship may be affected by magnesium intake (Bunce et al., 1965). In humans, long-term calcium supplementation did not adversely affect iron status as assessed by plasma ferritin concentrations in one study (Minihane and Fairweather-Tait, 1998), but other studies demonstrated a short-term reduction in iron absorption as dietary calcium increased (Cook et al., 1991; Hallberg et al., 2000).
For many years, salt mixes (mineral premixes of published composition) have been successfully used in laboratory primate diets (Hegsted et al., 1941; Hayes et al., 1980; Hawk et al., 1994). This information has been used to formulate commercial primate biscuits or pellets that appear to meet the mineral requirements of nonhuman primates. It is important to note that substantial deviations in mineral concentrations have been found among primate diets produced by different manufacturers, and between manufacturers’ published specifications and the mineral concentrations found by analysis (Wise and Gilburt, 1981).
The skeleton and teeth of mammals contain over 98% of the body’s calcium (Ca) and about 80% of the body’s phosphorus (P). Because of the relative mass and density of bones and teeth, Ca and P are required in large amounts, relative to other macrominerals. In addition to their critical structural role, Ca and P are essential for normal cellular communication and modulation.
Calcium binds to many cellular proteins, resulting in their activation. The functions of the proteins are diverse and include cell movement, muscle contraction, nerve transmission, glandular secretion, blood clotting, and cell division (Weaver and Heaney, 1999). When a cell, such as a muscle fiber, receives a nerve stimulus to contract, Ca channels in the plasma membrane open to admit a few Ca ions from the cytosol. The ions bind to an array of intracellular activator proteins that release a flood of Ca from intracellular storage vesicles (sarcoplasmic reticulum in the case of muscle). The increase in cytosolic Ca concentration leads to activation of the contraction complex. Troponin c, after binding Ca, initiates a series of steps leading to muscle contraction. Another Ca-binding protein, calmodulin, has many secondary messenger functions, one of which is to activate the enzymes that break down glycogen. Thus, Ca ions both trigger muscle contraction and fuel the process.
P is widely distributed in soft tissue and is required to drive multiple metabolic and energy reactions within and between cells. As phosphate, it helps to maintain osmotic and acid-base balance. As a component of deoxyribonucleic and ribonucleic acids, P is involved in cell growth and differentiation. As a phospholipid, it contributes to cell-membrane fluidity and integrity. Through involvement in creatine phosphate, adenosine triphosphate (ATP), and other phosphorylated compounds, P plays a vital role in energy transfer and use, gluconeogenesis, fatty acid transport, amino acid and protein synthesis, and activity of the sodium-potassium pump (Knochel, 1999).
Short-term, moderate inadequacies in Ca intake are modulated by skeletal reserves and cause few signs of deficiency, particularly in adults. However, rapidly growing young animals might exhibit hypocalcemia, hypercalciuria, and increased plasma alkaline phosphatase activity. Chronic, long-term dietary Ca deficiency can result in retarded growth and rickets in the young and osteomalacia and osteoporosis in adults.
Early responses to low dietary P include a decline in plasma inorganic P concentration and an increase in plasma alkaline phosphatase activity. If the deficiency is sufficiently severe or prolonged, abnormalities of the bones and teeth can be expected, growth will slow in the young, and appetite will be depressed; and pica (depraved appetite) will be seen in some domestic animals (Underwood and Suttle, 1999).
An early study of Ca metabolism in rhesus macaques concluded that a growing 3-kg monkey requires Ca at 150 mg·BWkg-1·d-1 (Harris et al., 1961). In later studies with rhesus macaques, feeding a diet containing 0.15% Ca (equivalent to Ca at 150 mg·BWkg-1·d-1 for 2- to 3-kg animals) resulted in osteoporosis (Griffiths et al., 1975). Fluoride added to such a diet at 50 ppm prevented osteoporosis by reducing bone growth rate and resorption, resulting in bones with normal density, but the added fluoride interfered with mineralization of osteoid, and led to osteomalacia.
When diets containing 0.32% Ca were fed to young cynomolgus monkeys for about 3½ years, motor neuron damage resulted; the damage was exacerbated by addition of aluminum and manganese to the diet (Garruto et al., 1989).
The minimal dietary Ca concentration of 0.5% (air-dry basis) previously recommended (National Research Coun-