Organ system studies gastrointestinal

These major organ systems must be studied because growth deficits are likely to appear only secondary to effects on specific organs or tissues and may not appear for some time after nutritional insult. For example, slow or inadequate growth is a common denominator of impaired gastrointestinal function, but it does not identify the function that is impaired. In addition, some organ systems (e.g., immune and endocrine) are immature at birth every effort must be made to ensure that ingredients new to infant formulas will not affect the development of these systems or the expression of their function. 

The incidence of associated anomalies is much higher if the horseshoe kidney is discovered in the newborn period. In postmortem examinations of 99 infants with horseshoe kidneys, 78% had malformations of other organ systems such as the central nervous system, the gastrointestinal tract, and the skeletal and cardiovascular system (Zondek and Zondek 1964). One-third of patients with horseshoe kidney had at least one other abnormality (Boatman et al. 1972). Several well-known syndromes are associated with fused kidney. Trisomy 18 has an incidence of 21% (Warkany et al. 1966 Boatman et al. 1972). In US studies, Lippe et al. (1988) noted horseshoe kidneys in 7% of patients with Turner s syndrome. In patients with neural tube defects, there is also an increased incidence of horseshoe kidneys (Whitaker and Hunt 1987). Nearly one-third of patients with a horseshoe kidney remain undiagnosed throughout life (Glenn 1959 Pitts and Muecke 1975). 

Sato et al. (1991) expanded their earlier PBPK model to account for differences in body weight, body fat content, and sex and applied it to predicting the effect of these factors on trichloroethylene metabolism and excretion. Their model consisted of seven compartments (lung, vessel rich tissue, vessel poor tissue, muscle, fat tissue, gastrointestinal system, and hepatic system) and made various assumptions about the metabolic pathways considered. First-order Michaelis-Menten kinetics were assumed for simplicity, and the first metabolic product was assumed to be chloral hydrate, which was then converted to TCA and trichloroethanol. Further assumptions were that metabolism was limited to the hepatic compartment and that tissue and organ volumes were related to body weight. The metabolic parameters, (the scaling constant for the maximum rate of metabolism) and (the Michaelis constant), were those determined for trichloroethylene in a study by Koizumi (1989) and are presented in Table 2-3. 

Target organs of chloroform toxicity are the central nervous system, liver, and kidneys (see Section 2.2). Respiratory, cardiovascular, and gastrointestinal toxic effects have also been reported. Studies in animals also indicated that chloroform exposure may induce reproductive and developmental effects and cause cancer. Several studies investigated the possible mechanism for chloroform-induced toxicity (see Section 2.5). Proposed mechanisms of chloroform toxicity and potential mitigations based on these mechanisms are discussed below. The potential mitigation techniques mentioned are all experimental. 

Several chronic inhalation and oral studies and acute dermal studies in animals are reported in the literature. These studies exposed several species of animals to both soluble and less-soluble nickel compounds. The target organs were found to be the respiratory system for inhalation exposure and the respiratory system, gastrointestinal tract, hematological system, and kidneys for oral exposure at high levels. Reproductive and developmental effects were observed in animals after inhalation exposure and after oral exposure to nickel. Nickel sensitivity and dermatitis were also observed. 

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