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At least 19 recordsLinked to original sources
PubMed1989

Effect of sodium saccharin and calcium saccharin on urinary parameters in rats fed Prolab 3200 or AIN-76 diet.

The effects of the salt form of saccharin and of diet on urinary ion levels have been studied in rats. Sodium saccharin (NaS) or calcium saccharin (CaS) was fed at a level of 5% in either Agway Prolab 3200 diet or AIN-76 diet to male, 5-wk-old F344 rats for 10 wk. The AIN-76 diet contained considerably less calcium, sodium and potassium than the Prolab 3200 diet, and smaller amounts of these ions were eliminated over 24 hr in the urine of rats fed the AIN-76 diet. Although food consumption was less in the groups fed AIN-76, total urinary saccharinate ion excretion with either saccharin salt was comparable with, or even higher than, that excreted by rats fed either salt in the Prolab 3200 diet. Rats fed Prolab 3200 eliminated approximately equal amounts of saccharinate ion in the faeces and urine. Rats fed AIN-76 eliminated about 10-20 times as much saccharin in the urine as in the faeces. Total saccharin excretion (faecal and urinary) was not influenced by the salt form. Water intake and urine volume were lower in rats fed control AIN-76 diet in comparison with those fed Prolab 3200, and were increased above the control level in groups fed saccharin in the AIN-76 diet. Urine electrolyte levels and osmolality were lower in the groups fed AIN-76. In general, NaS administration in either diet resulted in increased urinary sodium compared with controls, and the pH was at, or above, the level of control rats. CaS resulted in increased urinary calcium and decreased pH. There were marked diurnal variations in the urinary excretion of the various electrolytes, pH, and urine volume over a 24-hr period in all rats. This diurnal variation was more pronounced in the rats fed the Prolab 3200 diet. These results indicate that NaS and CaS have marked effects on the excretion of urinary electrolytes, and that these effects are influenced by diet.

Animal Feed↗
PubMed1991

Modulation of saccharin preference by morphine and naloxone: inversion of drug effects as a function of saccharin concentration.

The aim of the present study was to verify and extend a recent, isolated observation showing that, in rats, a moderate dose of morphine may induce either an increase or a decrease in preference for saccharin, the direction of the response depending apparently on the concentration of the sweetener. Two experiments were performed successively. First, we showed that the preference threshold for saccharin (0.3 mM, two-bottle procedure) of rats placed on a schedule of restricted water access was significantly decreased following injection of 1 mg/kg of morphine. In the second experiment, three groups of naive rats were submitted to the preference test but the concentration of saccharin solution was different for each group, namely 0.3, 1 and 1.7 mM. After stabilization of the baseline responses the effect of morphine (1 mg/kg) was tested in each of the 3 groups. As observed previously morphine decreased the preference of the rats tested with the 0.3 mM solution, but markedly increased the preference of the two other groups tested with the 1 and 1.7 mM solutions respectively. The effects of low doses of naloxone (0.01, 0.1 and 1 mg/kg) were then tested on the same groups of rats with the same saccharin concentrations. The 0.01 mg/kg dose of the antagonist increased the preference for the groups of rats tested with the 0.3 and 1 mM solutions. The other two doses of naloxone decreased saccharin intake whatever the saccharin concentration used. It is suggested that these apparently paradoxical effects of morphine and naloxone could result either from the stimulation of opioid autoreceptors or from the differential stimulation of different opioid receptor subtypes.

Animals↗
PubMed1991

Time-quality tracking of monosodium glutamate, sodium saccharin, and a citric acid-saccharin mixture.

The temporal patterns of taste-quality descriptors evoked by 1000-ms duration stimulus liquids flowed through a closed delivery system over the anterodorsal tongue tip region were indicated using touch-typing on a computer keyboard. Single keys corresponded to the taste words of a 23 item code. A computer monitor displayed for subjects the keys pressed and when they were pressed, starting at stimulus delivery. For 2 mM sodium saccharin (NaSac), 75% of the responses were "sweet," 6.5% "sugar"; for NaSac in 10 mM citric acid (ArtLem), 43% "sour," 20% "citrus," and 11% "sugar"; for 214 mM monosodium glutamate (MSG), 28% "salty," 14% "sour," and 10% 1st "soapy," then "no taste," and finally "bitter." Distilled water received "no taste" on all trials. Response durations were 657 ms for ArtLem, 594 ms for NaSac, 577 ms for MSG. MSG yielded multiple quality responses on 25.5% of the trials; ArtLem, 9%; and NaSac, 1%. These results are compared with temporal patterns for taste intensity and with unrestricted verbal descriptions of the solutions.

Adolescent↗
PubMed1987

Effect of pH and ions on the electronic structure of saccharin.

The sodium salt of saccharin is biologically more active as a urothelial cell mitogen in vivo, when fed to male rats, than are the potassium or calcium salts or the acid form, despite similar concentrations of saccharin excreted in the urine. The differences in bladder-mitogenic activity between sodium saccharin and the other salts of saccharin may be the result of known differences in the ionic composition of the urine of rats receiving these various forms of saccharin. These changes in the rat urine following administration of the different salts of saccharin could be responsible for the observed mitogenic responses to oral saccharin; alternatively the differences in the ionic composition of the urine could result in changes in the electronic structure of the saccharin molecule itself, allowing it to be more active in certain ionic environments. Since the pKa of saccharin is 1.8, essentially all of the saccharin in urine (pH greater than 5) will exist in the ionized form. We have used 17O, 15N, 13C and two-dimensional nuclear magnetic resonance (NMR) spectroscopy to explore the electronic structure of the saccharin molecule in aqueous solution. By observing the NMR spectra of the saccharinate ion in the presence of varying concentrations of hydrogen, potassium, sodium, calcium, magnesium, bicarbonate and urate, we have demonstrated that at physiological levels none of these ions significantly alters the electronic structure of the saccharin molecule. Hence the differences in the mitogenic response to the different saccharin salts cannot be explained by alterations in the structure of the saccharin molecule.

Carbon Isotopes↗
PubMed1978

Carcinogenicity of saccharin.

Saccharin is carcinogenic for the urinary bladder in rats and mice, and most likely is carcinogenic in human beings. The neoplasms of the urinary bladder are malignant and invade and metastasize. Male rats are more susceptible to urinary bladder carcinogenesis than female rats. Rats exposed as fetuses develop neoplasms more readily than rats exposed as weanlings. The lesions in the urinary bladder go through the stages of hyperplasia, hyperplastic nodules, and later carcinomas. The male of the human species ingesting saccharin, as for rats, is more susceptible to carcinogenesis of the urinary bladder than the female. Neoplasms of the urinary bladder in rats were not caused by stones, parasites, sodium, or impurities. There is a cocarcinogenic effect between saccharin and methylnitrosurea for the urinary bladder. Even through carcinomas of the urinary bladder are present in rats given the higher doses of saccharin, one was observed in a female rat given 0.5%. Chronic renal disease develops in rats ingesting saccharin. The disease is more advanced at the lower doses than at the higher doses, suggesting that saccharin at the lower doses does not reach the urinary bladder. Early neoplasms are seen in the renal pelvis of rats given the higher doses of saccharin. The risk ratios for urinary bladder carcinomas in human beings increase with both frequency andduration of saccharin usage. Benign and malignant neoplasms at all sites are significantly increased in mice and rats ingesting the higher doses of saccharin. These neoplasms are present in the reproductive and hematopoietic systems, and to a lesser extent in the lungs, vascular system and squamous epithelium. Neoplasms in some organs develop with the lower doses of saccharin. Lymphosarcomas of the lung are significantly increased in rats given 0.01% saccharin. Chronic renal disease in rats given saccharin interferes with the health and life span and consequently with development of neoplasms. Saccharin initiates neoplasms of the skin when its application is followed by croton oil. Epidemiological studies have not been done for neoplasms other than the urinary bladder in human beings.

Animals↗
PubMed1989

Drinking saccharin increases food intake and preference--III. Sensory and associative factors.

Rats that drink saccharin solution increase their short-term food intake and develop a preference for flavored food eaten when saccharin is ingested. Here we describe experiments that examined whether these changes in feeding behavior were due to learning and/or the reinforcing sensory properties of saccharin solution. It was found that learning was unnecessary for the feeding response, as rats that drank saccharin increased food intake whether or not their food contained saccharin-contingent flavor cues. However, learning helped support and maintain the response, as rats repeatedly given flavored food together with saccharin to drink later increased intake when given the flavored food without saccharin (i.e. in extinction). The rewarding or hedonic effects of the immediate orosensory properties of saccharin were not responsible for its effects on feeding, as drinking saccharin before but not after eating flavored food increased food intake and food preference. Furthermore, hungry rats developed an aversion to flavored food paired with saccharin ingestion when the quantity of food was limited. This implies that the flavored food preference produced by drinking saccharin involves an association between sensory aspects of the food and the metabolic consequences of food ingestion, which interact with a postingestive action of drinking saccharin that is related to the rat's metabolic state.

Animals↗
PubMed1990

The health risks of saccharin revisited.

Almost from its discovery in 1879, the use of saccharin as an artificial, non-nutritive sweetener has been the center of several controversies regarding potential toxic effects, most recently focusing on the urinary bladder carcinogenicity of sodium saccharin in rats when fed at high doses in two-generation studies. No carcinogenic effect has been observed in mice, hamsters, or monkeys, and numerous epidemiological studies provide no clear or consistent evidence to support the assertion that sodium saccharin increases the risk of bladder cancer in the human population. Mechanism of action studies in the one susceptible species, the rat, continue to provide information useful in assessing potential risk to the human from saccharin consumption. Unlike typical carcinogens which interact with DNA, sodium saccharin is not genotoxic, but leads to an increase in cell proliferation of the urothelium, the only target tissue. It also appears that the effect of saccharin is modified by the salt form in which it is administered, despite equivalent concentrations of saccharin in the urine. The chemical form of saccharin in the urine is unaffected, and there is no evidence for a specific cell receptor for the saccharin molecule. Changes in several urinary parameters, such as pH, sodium, protein, silicates, volume, and others, appear to influence the reaction of the urothelium to sodium saccharin administration. Silicon-containing precipitate and/or crystals appear to be generated in the urine under specific circumstances, acting as microabrasive, cytotoxic material. Using a mathematical model of carcinogenesis, which encompasses the temporal dynamics and complexity of the process at a cellular level, including spontaneous genetic transitions, it has been shown that the effects of sodium saccharin can be explained entirely in terms of its non-genotoxic influence on cell proliferation. In interpreting these analytical studies in the human context, particularly as they pertain to the urinary milieu which appears to be pivotal in the effect of sodium saccharin, we are led to the conclusion that there is a threshold effect in male rats and that an effect on the human urothelium is unlikely at even the highest levels of human consumption.

Animals↗
PubMed1987

Caffeine enhancement of saccharin but not cyclamate flavor avoidance.

The present experiments were designed to assess whether caffeine, a substance that potentiates human perception of some artificial sweeteners, might also enhance perception of such substances by rats. In Experiment 1, rats were given varied concentrations of saccharin, cyclamate, and caffeine in 2-choice tests. 'Indifference thresholds' for these substances were 3.9 X 10(-4) M, 1 X 10(-3) M, and 1.6 X 10(-7) M, respectively. In Experiment 2, concentrations of saccharin and cyclamate just above and below indifference were used as stimuli in a flavor avoidance learning (FAL) paradigm. 'Suprathreshold' concentrations of saccharin and cyclamate produced reliable FAL while 'subthreshold' concentrations did not. In Experiment 3, rats were exposed to a low concentration of caffeine followed by presentations of subthreshold concentrations of saccharin or cyclamate as stimuli in a FAL paradigm. Saccharin FAL was observed but cyclamate FAL was not, suggesting that caffeine preexposure selectively potentiated detection of saccharin. In Experiment 4, animals were given saccharin or cyclamate with or without prior exposure to caffeine in a FAL paradigm. During subsequent tests, animals were presented with saccharin or cyclamate following exposure to caffeine saccharin or cyclamate mixed with caffeine saccharin or cyclamate alone. Saccharin FAL was observed following caffeine preexposure, but mixing with caffeine had no effect. These findings of selective potentiation are consistent with previous studies of human sensitivity after caffeine preexposure. Moreover, the present results support the notion that inhibitory A1 adenosine receptors are involved in modulating the perceived intensity of some flavors.

Animals↗
PubMed1987

Influence of saccharin on Polycose, sucrose, and glucose intake and preference in rats.

The effect of adding 0.125% saccharin to 3% or 32% solutions of Polycose, sucrose and glucose on the fluid intake and preference of adult female rats was examined. In Experiment 1, the rats consumed more of a 3% Polycose + 0.125% saccharin solution (P + s) than of either a 3% Polycose or 0.125% saccharin solution; similar results were obtained with sucrose + saccharin (S + s) and glucose + saccharin (G + s) solutions. The polydipsic effects of the P + s, S + s, and G + s solutions were comparable (225 to 278 ml/day). Adding saccharin to 32% Polycose, sucrose, or glucose solutions did not increase solution intake. In two-solution preference tests, though, the rats preferred the 32% Polycose + saccharin and 32% glucose + saccharin solutions to 32% Polycose and 32% glucose solutions, respectively. Saccharin did not reliably affect the preference for the 32% sucrose solution. In Experiment 2, the preference for 3% carbohydrate solutions was assessed using two-solution tests. The rats preferred 3% sucrcose to 3% Polycose or 3% glucose; they also preferred 3% Polycose to 3% glucose. When saccharin was added to the solutions, the rats displayed equal preferences for the S + s and P + s solutions, and for the P + s and G + s solutions but they strongly preferred the S + s to the G + s solution. Recent findings suggest that polysaccharides such as Polycose taste qualitatively different from sucrose and saccharin to rats, i.e., have a "nonsweet" taste.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

The effect of saccharin ingestion on the excretion of microbial amino acid metabolites in rat and man.

Low dietary levels of sodium saccharin (0-2%) fed to male rats for 6 weeks produced a dose-related increase in the urinary excretion of p-cresol, a major microbial metabolite of tyrosine. Some animals fed higher levels of saccharin (5-7.5%) for 6 weeks excreted increased amounts of p-cresol, but many excreted negligible amounts so that the overall dose-response relationship was bell shaped. After 20 weeks of exposure, all rats in the higher dose groups showed increased p-cresol excretion and by 26 weeks the 7.5% saccharin group showed a 36-fold increase over animals fed the 0% saccharin diet. The urinary excretion of phenol, another microbial amino acid metabolite, was constant in animals fed dietary levels of saccharin below 2% for 6 weeks, but was virtually abolished at higher levels. The excretion of indican (formed from indole, a microbial metabolite of tryptophan) was increased by saccharin in a dose-related fashion at all time points, but showed only a 3-fold increase at 7.5% compared with the 0% group. p-Cresol may therefore prove more sensitive than indican as an indicator of altered microbial metabolism due to saccharin. In a separate study the effect of 7.5% saccharin on p-cresol and indican excretion was shown to be largely reversible and the excretion of phenol increased rapidly when saccharin was withdrawn from the diet. Chronic saccharin administration to man at high doses (1 g/day for 4 weeks) had no perceptible effect on the excretion of these three metabolites.

Amino Acids↗
PubMed1989

Effects of Na saccharin feeding and urine on barrier properties of excised rat urinary bladder.

When male rats of certain strains are fed a diet with 3% or more Na saccharin, their urinary bladders develop epithelial hyperplasia and a greater incidence of tumors. Since the daily dose of saccharin is high, a link between tumor formation and the disruption of urothelial physiologic and biochemical processes has been sought. We fed male and female Sprague-Dawley rats a saccharin-free or 7.5% Na saccharin diet for 1 month. Excised bladders were mounted in flux chambers and exposed to Krebs-Ringer bicarbonate solution (KRB) or urine. Bioelectric properties and 22Na, 36Cl, and [14C]mannitol or [3H]mannitol unidirectional fluxes were measured by conventional techniques. No differences were noted between bladders from male and female animals or between Na saccharin-fed animals and animals fed the saccharin-free diet. When both surfaces of the epithelium were exposed to KRB, transepithelial dc conductance fell over 4 hr to 50% of the initial value. Conductance averaged 1.4 mS/cm2. Transepithelial potential difference (PD) was usually lumen negative and averaged 0.7 mV. Unidirectional permeability coefficients for 36Cl, 22Na, and radiomannitol were symmetric, proportional to conductance, and followed a rank order compatible with unrestricted passive diffusion. Exposure of the bladder lumen to urine from animals fed saccharin-free or Na saccharin diet hyperpolarized the transepithelial PD by more than 5 mV and raised conductance nearly threefold. Permeability coefficients remained symmetric and compatible with passive diffusion. Exposure of the lumen to solutions with the K+, Na+, and Cl concentrations and osmolality of urine simulated the conductance and PD effects of urine. We conclude that Na saccharin feeding or urine with saccharin does not uniquely affect the permeability of the excised preparation. Small hydrophilic solutes appear to cross the bladder epithelium through paracellular channels which increase in aggregate area during exposure of the lumen to urine. The hyperpolarization induced by lumenal urine is the consequence of the transepithelial K+ gradient.

Animals↗
PubMed1979

Response of the rat to saccharin with particular reference to the urinary bladder.

Male and female Wistar rats were administered sodium saccharin for life (2 yr) either in the drinking water or diet. The maximum palatable dose of saccharin in the drinking water was found to be 2 g/kg/day and, even then, there was some voluntary restriction of fluid intake in the males. By contrast, double this dose--namely 4 g/kg/day, was palatable in the diet. A control group of rats of both sexes received saccharin-free diet and drinking water. Mild urothelial hyperplasias developed from 85 weeks in rats of both sexes receiving saccharin either in the drinking water or diet; the incidence was statistically significant in both the bladders and kidneys of rats receiving the higher dose of saccharin in the diet, but in the kidneys only of rats receiving the lower dose of saccharin in the drinking water. Telangiectasia of the vasa recta was significant in saccharin-treated rats of both sexes at both doses. A very low incidence of bladder tumours, exclusively in males receiving the higher saccharin dose in the diet was seen from 95 weeks. No consistent relationship between bladder epithelial hyperplasias and crystalluria could be demonstrated, although all 3 bladder tumours were associated with some form of mineralisation. Results suggest a particular susceptibility of males to saccharin treatment. The possibility that saccharin may promote, or enhance, the development of latent tumour cells already present in the experimental population, rather than initiate carcinogenesis per se is considered.

Animals↗
PubMed1988

Uptake of saccharin and related intense sweeteners by Streptococcus mutans NCTC 10449.

In a 1-octanol/phosphate buffer system, saccharin was much more lipophilic than would be inferred from its dissociation constant which, however, determined the partition behavior of acesulfame and cyclamate. The uptake of saccharin into Streptococcus mutans led to a 30 to 40-fold higher concentration of this intense sweetener within cells than in the incubation medium. Acesulfame and cyclamate were distributed between cells and medium essentially in a diffusion-controlled manner. The uptake of saccharin into S. mutans was found to depend strongly on simultaneous sugar fermentation, and in addition, on external pH, sweetener concentrations, and cell densities. Without glycolysis, caused, for example, by an exhaustion of added sucrose, too acidic external pH, or the addition of glycolysis inhibitors, the uptake of saccharin was diffusion-controlled as in the case of acesulfame and cyclamate. The uptake of saccharin was inhibited by a reversal of the direction of the lactate gradient from in----out to out----in. The activation energy of saccharin uptake into glycolyzing S. mutans was near 18 kJ/mol, while glycolysis itself required 82-98 kJ/mol as activation energy, depending somewhat on experimental conditions. Up to 100 attomol of saccharin per bacterial cell was observed. It was concluded that the cytomembrane of S. mutans was involved in mediating the inhibitory effects of saccharin by an antiport of saccharin into cells in exchange for lactate.

Chromatography, High Pressure Liquid↗
PubMed1989

Drinking saccharin increases food intake and preference--II. Hydrational factors.

Rats that drink saccharin solution increase their short-term food intake and develop a preference for flavored food eaten when saccharin is ingested. In this paper, we examined whether these changes in feeding behavior were due to overhydration resulting from drinking hyposmotic saccharin solution. Consistent with this possibility, the short-term food intake of rats was increased by drinking hyposmotic 0.2% saccharin dissolved in water, unaffected by drinking isosmotic 0.9% NaCl, and decreased by drinking 0.2% saccharin dissolved in 0.9% NaCl. In addition, rats showed a sustained increase in saccharin-induced food intake after antidiuretic hormone treatment, which was designed to exacerbate their positive water balance. Less consistent with a hydrational explanation of saccharin-induced feeding was the finding that rats drinking only 2ml 0.2% saccharin solution increased food intake. Also, gastric intubation of similar volumes of water produced a small, transient increase in feeding behavior, which was apparent after the first intubation only and could not be preserved by adding water-contingent flavors to the food. Taken together, these results suggest that the hydrational effects of drinking hyposmotic saccharin solution contribute to, but cannot account for, the increase in food intake. Hydration had no observable influence on the acquisition of flavored food preference.

Animals↗
PubMed1989

Drinking saccharin increases food intake and preference--IV. Cephalic phase and metabolic factors.

Rats that drink saccharin solution increase their short-term food intake and develop a preference for flavored food eaten when saccharin is ingested. In this paper, we examined whether these effects are mediated by cephalic-phase metabolic reflexes. The results show that the cephalic-phase insulin response could be dissociated from food intake in three ways. (1) Drinking saccharin increased the food intake and food preference of rats with sham surgery (SHM) or celiac vagotomy (CV), but not hepatic vagotomy (HV); it produced a short-lived increase in plasma insulin levels in all three groups, but the insulin response of both the CV and HV group was attenuated relative to the SHM group. (2) Rats increased food intake even when a 90 min interval was imposed between drinking saccharin and eating food, although insulin and glucose levels returned to normal within 30 min of drinking saccharin. (3) Streptozotocin-induced diabetes did not affect the increased feeding response to saccharin. The failure of rats given hepatic vagotomy to increase food intake and food preference when drinking saccharin suggests that a hepatic mechanism is involved. We propose that drinking saccharin increases food intake by temporarily altering the disposition of metabolic fuels towards storage and away from oxidation. Flavored food eaten after drinking saccharin becomes preferred because it provides fuel to counteract this reduction in oxidation.

Animals↗
PubMed1986

The effects of saccharin on the development of neoplastic lesions initiated with N-methyl-N-nitrosourea in the rat urothelium.

Saccharin has been reported to induce urinary bladder tumors in multigeneration rat feeding studies and to promote bladder carcinogenesis in rats initiated with known bladder carcinogens. To examine the dose-dependent effects of saccharin on tumor promotion, sodium saccharin was administered at six levels in the diet (5.0, 2.5, 1.0, 0.5, 0.1, and 0%) to female Sprague-Dawley rats which had received, by trans-urethral instillation into the bladder, either a single dose of saline or an initiating dose of N-methyl-N-nitrosourea (MNU), a potent direct-acting carcinogen. Additional groups with and without MNU treatment received sodium saccharin (2%) in the drinking water, acid-saccharin (5%) in the diet, or MNU, four weekly doses, as a positive control. Histopathologic examination of the urinary bladders from dead and moribund animals and from animals sacrificed after 102 weeks on dose was performed, and benign papillomas were commonly observed in those animals given MNU. A statistical analysis of the lesions indicated an increase in tumor incidence and a decrease in time to tumor with increasing saccharin dose in dead and moribund animals. This response was observed in the dose series of 0 to 2.5% saccharin in the diet. Dead and moribund animals which had received 5% sodium saccharin exhibited few tumors. An increasing incidence of tumors in MNU-treated control animals was observed during the final weeks of the study. Although this increase in background tumors in senescent animals complicated the interpretation of the total tumor incidences, the results in dead and moribund animals (about 60% of the total) indicated that saccharin served as a tumor promoter in this two-stage carcinogenesis model system by decreasing the latency period of the lesions.

Animals↗
PubMed1990

Effects of different types of diet and sodium saccharin on proliferation at the limiting ridge of the rat forestomach.

Sodium saccharin, at high doses in the diet, has been reported to cause hyperplasia of the forestomach (squamous portion of stomach), at the limiting ridge in F344 rats, in addition to its potential to induce proliferative effects on the urinary bladder epithelium. We have characterized this hyperplasia of the squamous epithelium of the forestomach at the limiting ridge in F344 and Sprague-Dawley rats given various doses of sodium saccharin for 4 to 95 wk. With increasing doses of sodium saccharin, the limiting ridge of the forestomach showed dose-related morphological changes: basal-cell hyperplasia, early papillary hyperplasia with basal-cell hyperplasia and papillary hyperplasia. Calcium saccharin in Prolab diet caused hyperplasia of the forestomach at the limiting ridge, similar to that caused by sodium saccharin. The severity of hyperplasia was influenced by the type of diet and by the strain of rats. AIN-76A diet without added sodium saccharin caused basal-cell hyperplasia in F344 rats, whereas Prolab, Purina and NIH-07 diets without added sodium saccharin had little or no effect on the forestomach. The effect of AIN-76A diet alone persisted through 95 wk of feeding without any evidence of tumour formation. In Sprague-Dawley rats, which appeared more sensitive to effects on the forestomach than F344 rats, Prolab 3200 and Purina diets without sodium saccharin caused basal-cell hyperplasia in more than half of the treated rats. The forestomach hyperplasia associated with AIN-76A or saccharin administration appears to be mild, limited in extent to the limiting ridge, and not associated with carcinogenesis.

Animal Feed↗
PubMed1978

Renal tubular transport of saccharin.

These experiments were designed to examine the mechanisms involved in the renal excretion of the non-nutritive sweetener, saccharin. Renal transport of saccharin in female rats was quantitatively evaluated using renal cortical slices in vitro and renal clearances in vivo. Renal cortical slices actively accumulated saccharin. Accumulation was oxygen dependent, saturable and reduced in the presence of metabolic inhibitors (2,4-dinitrophenol and sodium azide) and other organic anions 1p-aminohippurate (PAH) and probenecid]. Furthermore, addition of acetate or lactate to the medium stimulated saccharin uptake whereas reducing potassium concentration in the medium significantly decreased saccharin accumulation. Addition of saccharin to medium containing PAH and N-methylnicotinamide produced a dose-related depression of PAH accumulation. Although N-methylnicotinamide accumulation also was reduced, the depression was not dose-related. The saccharin/inulin clearance ratio of 3.76 indicates that saccharin, like PAH, undergoes tubular secretion. These findings suggest that the primary route of renal elimination of saccharin is active tubular secretion. It is also suggested that saccharin and PAH may share a common transport system.

Animals↗