Humans excretion

Najjar and co-workers58 found on diets furnishing only 60 to 90 ig. of riboflavin per day that the urinary excretion (human) was about twice the intake, and the fecal excretion was about 5 to 6 times the intake. This indicates that for certain individuals on certain diets synthesis of riboflavin by intestinal organisms is sufficient to take care of the entire riboflavin needs. The authors conclude that riboflavin may not be a dietary essential in all cases. If this finding is valid, it certainly points to the probability that human needs vary widely because riboflavin deficiencies in human beings have been observed a great many times on many different types of diets. 

Absorption, Distribution, Metabolism, and Excretion. Human data indicate that chloroform absorption from the lungs is rapid and fairly complete (Smith et al. 1973). The data also indicate that absorption after oral exposure is fairly complete for both animals and humans (Brown et al. 1974a Fry et al. 1972 Taylor et al. 1974). Although there are no experimental data regarding dermal absorption in humans, some data have been extrapolated from mouse studies (Tsumta 1975). The rate of absorption following oral or inhalation exposure is rapid (within 1-2 hours). Additional animal studies investigating the rate of dermal absorption would be useful to quantitate dermal absorption and to compare information from oral and inhalation studies. 

Mammals other than primates further oxidize urate by a liver enzyme, urate oxidase. The product, allantoin, is excreted. Humans and other primates, as well as birds, lack urate oxidase and hence excrete uric acid as the final product of purine catabolism. In many animals other than mammals, allantoin is metabolized further to other products that are excreted Allantoic acid (some teleost fish), urea (most fishes, amphibians, some mollusks), and ammonia (some marine invertebrates, crustaceans, etc.). This pathway of further purine breakdown is shown in figure 23.22. 

After excretion, human pharmaceuticals and metabolites enter into wastewater. They are often not removed within wastewater treatment—if it is in place at all. Until recently, there wasn t any knowledge of the fact that pharmaceuticals, contrast media and others constitute a new type of environmental pollution and a possible health risk for the consumer and the environment. 

Toxicity. Fluoroborates are excreted mostly in the urine (22). Sodium fluoroborate is absorbed almost completely into the human bloodstream and over a 14-d experiment all of the NaBF ingested was found in the urine. Although the fluoride ion is covalently bound to boron, the rate of absorption of the physiologically inert BF from the gastrointestinal tract of rats exceeds that of the physiologically active simple fluorides (23). 

Heavy metals are of importance in human toxicity because the body possesses only inactive mechanisms for their excretion thus chronic, low level intakes can accumulate to toxic proportions. Treatment has likewise been relatively unsuccessfiil, except for symptomatic reHef. No effective means has been discovered to increase excretion. 

Phase I. This involves general testing for human pharmacology in healthy volunteers, ie, safe-dose adjustment deterrnination of absorption, metabohsm, and excretion patterns and monitoring for side effects. Usually fewer than 10 test subjects ate involved. 

Biosynthesis of Protein. The dynamic equilibrium of body protein was confirmed by animal experiments using A/-labeled amino acids in 1939 (104). The human body is maintained by a continuous equilibrium between the biosynthesis of proteins and their degradative metabolism where the nitrogen lost as urea (about 85% of total excreted nitrogen) and other nitrogen compounds is about 12 g/d under ordinary conditions. The details of protein biosynthesis in living cells have been described (2,6) (see also Proteins). 

The dermal adsorption of DEBT in humans has been studied in the Netherlands by appHcation of DEBT as undiluted technical material or as 15% solutions in alcohol. Labeled material was recovered from the skin, and absorption of DEBT was indicated by the appearance of label in urine after two hours of skin exposure. About 5—8% of the appHed treatments was recovered as metaboHtes from urine, and excretion of metaboHtes in the urine came to an end four hours after exposure ended. DEBT did not accumulate in the skin, and only a small (less than 0.08%) amount ended up in feces. Curiously, less has been absorbed through skin from 100% DEBT appHcation (3—8%, mean of 5.6%) than from 15% alcohol appHcation (4—14%, mean of 8.4%). These results have been described as consistent with previous absorption/metaboHsm studies using guinea pigs, rats, and hairless dogs. Other pubHcations on DEBT toxicology have been cited (92). 

Absorption of mannitol (209), sorbitol (210), and xyfltol (4) from the intestinal tract is relatively slow, compared to that of glucose. In humans, approximately 65% of orally adrninistered mannitol is absorbed in the dose range of 40—100 g. About one-third of the absorbed mannitol is excreted in the urine. The remainder is oxidized to carbon dioxide (211). 

Tb allium, which does not occur naturaHy in normal tissue, is not essential to mammals but does accumulate in the human body. Levels as low as 0.5 mg/100 g of tissue suggest thallium intoxication. Based on industrial experience, 0.10 mg /m of thallium in air is considered safe for a 40-h work week (37). The lethal dose for humans is not definitely known, but 1 g of absorbed thallium is considered sufficient to kHl an adult and 10 mg/kg body weight has been fatal to children. In severe cases of poisoning, death does not occur earlier than 8—10 d but most frequently in 10—12 d. Tb allium excretion is slow and prolonged. For example, tb allium is present in the feces 35 d after exposure and persists in the urine for up to three months. 

Relatively Httie is known about the bioavailabiUty of pantothenic acid in human beings, and only approximately 50% of pantothenic acid present in the diet is actually absorbed (10). Liver, adrenal glands, kidneys, brain, and testes contain high concentrations of pantothenic acid. In healthy adults, the total amount of pantothenic acid present in whole blood is estimated to be 1 mg/L. A significant (2—7 mg/d) difference is observed among different age-group individuals with respect to pantothenic acid intake and urinary excretion, indicating differences in the rate of metaboHsm of pantothenic acid. 

Thiamine requirements vary and, with a lack of significant storage capabiHty, a constant intake is needed or deficiency can occur relatively quickly. Human recommended daily allowances (RDAs) in the United States ate based on calorie intake at the level of 0.50 mg/4184 kj (1000 kcal) for healthy individuals (Table 2). As Httle as 0.15—0.20 mg/4184 kJ will prevent deficiency signs but 0.35—0.40 mg/4184 kJ are requited to maintain near normal urinary excretion levels and associated enzyme activities. Pregnant and lactating women requite higher levels of supplementation. Other countries have set different recommended levels (1,37,38). 

The recommended daily allowance for vitamin E ranges from 10 international units (1 lU = 1 mg all-rac-prevent vitamin E deficiency in humans. High levels enhance immune responses in both animals and humans. Requirements for animals vary from 3 USP units /kg diet for hamsters to 70 lU /kg diet for cats (13). The complete metaboHsm of vitamin E in animals or humans is not known. The primary excreted breakdown products of a-tocopherol in the body are gluconurides of tocopheronic acid (27) (Eig. 6). These are derived from the primary metaboUte a-tocopheryl quinone (9) (see Eig. 2) (44,45). 

The presence of nucleic acids ia yeast is oae of the maia problems with their use ia human foods. Other animals metabolize uric acid to aHantoia, which is excreted ia the uriae. Purines iagested by humans and some other primates are metabolized to uric acid, which may precipitate out ia tissue to cause gout (37). The daily human diet should contain no more than about 2 g of nucleic acid, which limits yeast iatake to a maximum of 20 g. Thus, the use of higher concentrations of yeast proteia ia human food requires removal of the nucleic acids. Unfortunately, yields of proteia from extracts treated as described are low, and the cost of the proteia may more than double. 

ACE inhibitors lower the elevated blood pressure in humans with a concomitant decrease in total peripheral resistance. Cardiac output is increased or unchanged heart rate is unchanged urinary sodium excretion is unchanged and potassium excretion is decreased. ACE inhibitors promote reduction of left ventricular hypertrophy. 

Citric acid occurs widely in the plant and animal kingdoms (12). It is found most abundantiy in the fmits of the citms species, but is also present as the free acid or as a salt in the fmit, seeds, or juices of a wide variety of flowers and plants. The citrate ion occurs in all animal tissues and fluids (12). The total ckculating citric acid in the semm of humans is approximately 1 mg/kg body weight. Normal daily excretion in human urine is 0.2—1.0 g. This natural occurrence of citric acid is described in Table 7. 

About 50% of copper in food is absorbed, usually under equitibrium conditions, and stored in the tiver and muscles. Excretion is mainly via the bile, and only a few percent of the absorbed amount is found in urine. The excretion of copper from the human body is influenced by molybdenum. A low molybdenum concentration in the diet causes a low excretion of copper, and a high intake results in a considerable increase in copper excretion (68). This copper—molybdenum relationship appears to correlate with copper deficiency symptoms in cattle. It has been suggested that, at the pH of the intestine, copper and molybdate ions react to form biologically unavailable copper molybdate (69). 

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