Olestra has been shown to be safe for its intended use by extensive testing in animals and in humans. It is not digested or absorbed and has no effect on the structure or physiology of the GI tract, the only organ of the body that it contacts. Olestra can interfere with the absorption of other lipophilic substances from the GI tract. The interference occurs because a portion of those molecules that are sufficiently lipophilic partition into the nonabsorbed olestra and is carried out of the body. Whether olestra will interfere with the absorption of a specific molecule can be predicted from the octanol-water partition coefficient of the molecule, a parameter that can be measured or calculated from a knowledge of the structure of the molecule. Olestra does not affect the absorption or efficacy of oral drugs because, in general, they are not sufficiently lipophilic to partition into the olestra. Olestra does not affect the absorption of water-soluble micronutrients or the absorption and utilization of macronutrients. Olestra can reduce the absorption of the fat-soluble vitamins when olestra foods and the vitamins are coingested. These effects can be offset by adding specific amounts of the vitamins to foods made with olestra. Other than the carotenoids and vitamins A and E, olestra does not affect the absorption of potentially beneficial components of fruits and vegetables. The effects on the vitamins can be offset by adding the vitamins to olestra foods. The reduction in the absorption of carotenoids will be less than 6-10% when olestra snacks are eaten under free-living dietary patterns. Any effect this reduction has on vitamin A status can be offset by addition of vitamin A to the foods. The absorption of flavonoids, polyphenols, and most other phytochemicals in fruits and vegetables, which have been shown to provide beneficial health effects, will not be affected by olestra because they are not sufficiently lipophilic. Individuals consuming large quantities of olestra may experience mild or moderate common GI symptoms such as loose or soft stools, gas, or nausea, symptoms similar to those experienced with certain other foods or changed dietary habits. When olestra snack foods are eaten under free-living dietary patterns, the symptoms are not different from those experienced when eating full-fat snack products, in either incidence or severity. When they are experienced, the symptoms resolve in 1-2 days, but may recur. They do not worsen with continued or increased olestra consumption and pose no health risk to the consumer. Olestra products will carry an information label alerting consumers to the possibility of GI symptoms. Olestra foods provide an additional option to those individuals who want or need to lower their total energy intake and body weight. These individuals will find it easier to change dietary habits and to maintain healthful nutritional practices when they use olestra foods. For those who want or need to reduce fat intake but not lose weight, olestra foods can reduce fat intake without affecting...

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The major site at which vinyl cysteine conjugates exert nephrotoxicity is the proximal tubule. Since this is the site of all active anion and cation transport, tubule transport integrity was used to assess nephrotoxicity. Tubules were isolated from young rabbits to study the in vivo and in vitro nephrotoxicity of the conjugate, dichlorovinyl cysteine (DCVC). In vivo exposure to DCVC caused necrosis in the pars recta region of the proximal tubules (20-100 mg/kg ip) and a dose-dependent decrease in tubular active transport. Addition of DCVC to the perfused kidney and tubule suspensions resulted in similar decreases in tubular organic ion transport. At 0.01 mM DCVC, transport was similar to controls while 1 mM DCVC completely inhibited active accumulation of the organic ions. Thus kidney tubule active transport is similarly inhibited in vivo and in vitro by DCVC indicating that bioactivation of DCVC and inhibition of active transport occur directly in the renal tubule.

Three linear polycarboxylate compounds, two linear polyacrylates (90,000 MW and 4,500 MW) and one linear polyacrylate-maleate copolymer (12,000 MW), were tested for their teratogenic potential in female Sprague Dawley rats. These polymers, which were tested as sodium salts, are used as dispersing agents in detergent formulations at levels of 1-5%. All compounds were administered by gavage during organogenesis (days 6-15 of pregnancy). No adverse effects on development were seen with any of the three compounds at any of the doses tested. The highest dose, and therefore the minimum no-effect dose, for the three linear polymers was 1125 mg/kg/day for the 90,000 MW polyacrylate, 3000 mg/kg/day for the 4,500 MW polyacrylate, and 6670 mg/kg/day for the polyacrylate-maleate copolymer. Based on these data, these compounds are not developmentally toxic, even at very high dose levels.

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