The potential developmental neurotoxicity of calcium cyclamate in CD rats.

The developmental neurotoxicity of calcium cyclamate was evaluated in Sprague Dawley [Crl:CD(SD)] rats, administered in drinking water, in comparison to a concurrent control group (water) and a positive control group given propylthiouracil (PTU). Calcium cyclamate was administered to F0 females for 4 weeks prior to pairing, throughout mating, gestation and lactation and to F1 offspring from weaning to 12 weeks of age, PTU was administered by gavage to F0 females from Day 6 of gestation up to Day 20 of lactation. Target calcium cyclamate doses were 0, 250, 500 and 1,000 mg/kg bw/day, while the PTU dose was 0.5 mg/kg bw/day. No treatment-related effects of cyclamate were observed in either the F0 or F1 generations on reproductive performance or neurobehavioral development. In comparison, PTU exposure resulted in developmental delays, memory impairment and a number of neuropathological and morphometric outcomes. The results from the unique developmental neurotoxicity study design, corroborate the absence of hyperactivity and any other neurotoxic effects following cyclamate administration at levels up to 878 mg/kg bw/day in F0 females and 784 mg/kg bw/day in F1 animals. This demonstrates the suitability of PTU as a positive control and confirms the safe use of cyclamate as a no-calorie sweetener.

Comparación del consumo de edulcorantes no nutritivos con estado nutricional en embarazadas chilenas / Comparison of non-nutritive sweetener consumption and nutritional status among pregnant Chileans

INTRODUCCIÓN: El consumo de edulcorantes no calóricos (ENC) se ha incrementado en todos los grupos etarios, sin embargo, no se ha cuantificado su ingesta en embarazadas OBJETIVO: Determinar la ingesta y comparar el consumo de ENC según el estado nutricional en embarazadas chilenas. MATERIAL Y MÉTODOS: Estudio descriptivo, se entrevistaron a embarazadas de las ciudades de Santiago y Concepción. A cada embarazada se le aplicó una encuesta de frecuencia de consumo semanal de alimentos con ENC para determinar la ingesta de ellos, y se les realizó una evaluación nutricional utilizando la información del carné de control de la embarazada. RESULTADOS: Se evaluaron 601 embarazadas, 98% consume ENC, ninguna de ellas sobrepasa la ingesta diaria admitida (IDA) para ningún ENC. Las bebidas y jugos con ENC presentan la mayor penetración de productos con ENC de la dieta. Al comparar según estado nutricional, no se encontraron diferencia en el consumo de los ENC. Al comparar solo las bebidas y jugos con ENC con ciclamato las embarazadas obesas consumen significativamente más. CONCLUSIÓN: No se observó diferencias según estado nutricional cuando se analiza de manera global, al analizar por grupos de alimentos el mayor consumo se observo en bebidas con ciclamato en las embarazadas con obesidad.

INTRODUCTION: Consumption of non-caloric sweeteners (NCS) has increased in all age groups; however, intake in pregnant women has not been quantified. OBJECTIVE: To determine the intake of NCS and compare consumption by nutritional status among pregnant Chileans. MATERIAL AND METHODS: Pregnant women from the cities of Santiago and Concepción were interviewed as part of a descriptive study. Each pregnant woman was given a frequency survey of weekly food consumption with NCS to determine intake, and a nutritional evaluation was carried out using information from the pregnant woman's check up form. RESULTS: 601 pregnant women were evaluated, 98% consumed NCS, none of them exceeded the accepted daily intake (ADI) for any NCS. Beverages and juices with NCS presented the highest proportions of NCS in the diet. When comparing nutritional status, no difference was found in the consumption of NCS. When comparing only beverages and juices with NCS, obese pregnant women consumed significantly more cyclamate compared to non-obese women. CONCLUSION: No differences according to nutritional status were observed when analyzed globally, when analyzing by food groups the highest consumption was observed in beverages with cyclamate among obese pregnant women.

Consumption of non-caloric sweeteners among pregnant Chileans: a cross-sectional study.

INTRODUCTION: Introduction: consumption of non-caloric sweeteners (NCS) has increased worldwide in the last 35 years. Objective: to determine the consumption of NCS among pregnant Chilean women and measure if consumption exceeded the acceptable daily intake. Methods: we conducted a cross-sectional study of pregnant women from the two main cities in Chile. Women were interviewed to determine the consumption of NCS and socioeconomic level; anthropometry was measured. Results: six hundred and one pregnant women were interviewed; 98% of pregnant women surveyed consumed NCS. The most consumed sweetener was sucralose (95.6%), followed by acesulfame k (80.6%), stevia (78.3%), aspartame (75.1%), saccharin (14.8%), and cyclamate (10%). We observed that consumption closest to the acceptable daily intake was reported for stevia (82.5%), followed by acesulfame k (44%). However, except stevia, which reached 12%, average values were under 5% of the acceptable daily intake. No pregnant woman in the sample exceeded the acceptable daily intake and there were no differences in sweetener consumption by trimester of pregnancy or by socioeconomic level. Conclusions: a high prevalence of NCS consumption was observed, however, none of the pregnant women exceeded the acceptable daily intake.

INTRODUCCIÓN: Introducción: el consumo de edulcorantes no calóricos (ENC) ha aumentado en todo el mundo en los últimos 35 años. Objetivo: determinar el consumo de ENC en embarazadas chilenas y medir si el consumo excede la ingesta diaria admisible (IDA). Métodos: realizamos un estudio transversal en embarazadas, proveniente de las dos principales ciudades de Chile. Se las entrevistó para determinar el consumo de ENC y nivel socioeconómico, además se realizó antropometría. Resultados: se entrevistaron a 601 embarazadas; el 98% de las embarazadas encuestadas consumieron ENC. El edulcorante más consumido fue sucralosa (95,6%), seguido de acesulfamo k (80,6%), estevia (78,3%), aspartamo (75,1%), sacarina (14,8%) y ciclamato (10%). Observamos que el consumo más cercano a la IDA se reportó para la estevia (82,5%), seguido de acesulfamo k (44%). Sin embargo, excepto la estevia, que alcanzó el 12% de adecuación con respecto al IDA, los valores promedio estuvieron por debajo del 5% de la IDA. Ninguna mujer embarazada en la muestra excedió la IDA y no hubo diferencias en el consumo de ENC por trimestre del embarazo o por nivel socioeconómico. Conclusiones: se observó una alta prevalencia de consumo de ENC, sin embargo, ninguna de las mujeres embarazadas excedió la IDA.

[Restless legs due to ingestion of 'light' beverages containing saccharine. Results of an N-of-1 trial]. / 'Restless legs' door inname van lightfrisdranken met sacharine. Resultaten van een N = 1-onderzoek.

To determine whether there was a connection between the complaint of restless legs and the ingestion of artificial sweeteners in a patient with these symptoms after drinking certain 'light' beverages, a randomised, double-blind, placebo-controlled N-of-1 trial with a crossover design was used. During a period of 48 days, the patient took 4 capsules per day containing either 150 mg of cyclamate, 22.5 mg of saccharine, both sweeteners, or placebo on two successive days. Between each of these 2-day periods there was a 2-day rest period during which no capsules were taken. The hospital pharmacist had prepared the capsules and determined the sequence of the 2-day periods on a random basis. The patient did not know which capsules he was taking. Every day on arising, starting 3 weeks before the trial period, the patient noted the intensity and duration of the symptoms in the late evening and previous night. For this notation he used an 11-point scale, from 0 (= no restless legs) to 10 (= almost total inability to sleep because of restless legs). A score of 1-3 corresponded to mild symptoms that had no effect on the patient's sleep; at a score of 4-6 his sleep was disturbed and at a score of 7-10 the patient hardly slept at all. The patient had symptoms more often while using saccharine or the combination of saccharine and cyclamate than when taking the placebo (4 and 4 versus 2 of the 6 nights); moreover, the average score was then statistically significantly higher (5.2 and 5.8 versus 3-3). It was concluded that there was a connection between the patient's complaints of restless legs and the use of saccharine, but not the use of cyclamate.

Estimated intake of intense sweeteners from non-alcoholic beverages in Denmark.

In 1999, 116 samples of non-alcoholic beverages were analysed for the intense sweeteners cyclamate, acesulfame-K, aspartame and saccharin. High contents of cyclamate close to the maximum permitted level in 1999 of 400 mg l(-1) were found in many soft drinks. The estimated intake of the sweeteners was calculated using the Danish Dietary Survey based on 3098 persons aged 1-80 years. The estimated intake with 90th percentiles of 0.7, 4.0 and 0.2 mg kg(-1) body weight (bw) day(-1) for acesulfame-K, aspartame and saccharin, respectively, was much lower than the acceptable daily intake (ADI) values of 15, 40 and 2.5 mg kg(-1) bw day(-1) for acesulfame-K, aspartame and saccharin, respectively. However, the 90th percentile of the estimated cyclamate intake in 1-3 year olds was close to the ADI value of 7 mg kg(-1) bw day(-1); and the 99th percentile in the 1-10 year olds far exceeded the ADI value. Boys aged 7-10 years had a significantly higher estimated intake of cyclamate than girls. The 90th percentile for the whole population was 1.8 mg kg(-1) bw day(-1). After the reduction in the maximum permitted level in the European Union in 2004 from 400 to 250 mg cyclamate l-1, the exposure in Denmark can also be expected to be reduced. A new investigation in 2007 should demonstrate whether the problem with high cyclamate intake is now solved.

Effects of sodium cyclamate on the rat placenta: a morphometric study

RESUMEN: El objetivo del trabajo fue determinar los efectos del ciclamato de sodio en la placenta de ratas, administrado durante el periodo de la embriogénesis. Fue administrado por vía intraperitoneal, en las ratas del grupo tratado, ciclamato de sodio en una dosis de 60 mg/Kg, desde el 10 al 14 día de gestación, siendo inyectado un volumen equivalente de solución salina en el grupo de ratas control. En el 20 día de preñez, 10 fetos (5 de cada grupo) fueron escogidos al azar para su estudio. Fue utilizada la técnica de cariometría para la evaluación de los parámetros nucleares de las células de las capas decidua, esponjosa y de las vellosidades coriónicas de la placenta de las ratas. El peso de los fetos tratados y de sus placentas fue menor que el del grupo control, así como también el funículo umbilical del grupo tratado fue más corto que el de los fetos controles. No hubo alteraciones en la capa de la decidua. En la capa esponjosa placentaria ocurrieron alteraciones de los siguientes parámetros: diámetro mayor, diámetro medio, perímetro, área, volumen, relación volumen/área y excentricidad. Los parámetros alterados en las vellosidades coriónicas fueron: diámetro medio, perímetro, área, volumen y relación volumen/área. El estudio demostró alteración placentaria con el uso del ciclamato de sodio en la rata preñada y su repercusión en el peso fetal y largo del funículo umbilical.

The intake of intense sweeteners - an update review.

Studies on the intakes of intense sweeteners in different countries published since the author's previous review in 1999 indicate that the average and 95th percentile intakes of acesulfame-K, aspartame, cyclamate and saccharin by adults are below the relevant acceptable daily intake (ADI) values. Fewer data are available for the newer sweeteners, sucralose and alitame, and because they are recent introductions to the market very low intakes were reported in those countries where they were available at the time of the intake study. Overall there has not been a significant change in the intakes of sweeteners in recent years. The only data indicating that the intake of an intense sweetener could exceed its ADI value were the 95th percentile intakes of cyclamate in children, particularly those with diabetes. This sub-group was identified as having high intakes of cyclamate in 1999, and recent studies have not generated reliable intake data to address this possibility.

[Restless legs due to ingestion of 'light' beverages containing saccharine; results of an N-of-1 trial]. / 'Restless legs' door inname van lightfrisdranken met sacharine; resultaten van een N = 1-onderzoek.

OBJECTIVE: To determine whether there was a connection between the complaint of restless legs and the ingestion of artificial sweeteners in a patient with these symptoms after drinking certain 'light' beverages. DESIGN: Randomised, double-blind, placebo-controlled N-of-1 trial with a cross-over design. METHOD: During a period of 48 days, the patient took 4 capsules per day containing either 150 mg of cyclamate, 22.5 mg of saccharine, both sweeteners, or placebo on two successive days. Between each of these 2-day periods there was a 2-day rest period during which no capsules were taken. The hospital pharmacist had prepared the capsules and determined the sequence of the 2-day periods on a random basis. The patient did not know which capsules he was taking. Every day on arising, starting 3 weeks before the trial period, the patient noted the intensity and duration of the symptoms in the late evening and previous night. For this notation he used an 11-point scale, from 0 (= no restless legs) to 10 (= almost total inability to sleep because of restless legs). RESULTS: A score of 1-3 corresponded to mild symptoms that had no effect on the patient's sleep; at a score of 4-6 his sleep was disturbed and at a score of 7-10 the patient hardly slept at all. The patient had symptoms more often while using saccharine or the combination of saccharine and cyclamate than when taking the placebo (4 and 4 versus 2 ofthe 6 nights); moreover, the average score was then statistically significantly higher (5.2 and 5.8 versus 3.3). CONCLUSION: There was a connection between the patient's complaints of restless legs and the use of saccharine, but not the use of cyclamate.

The metabolism of cyclamate to cyclohexylamine in humans during long-term administration.

A group of 14 subjects, who had been identified from 261 volunteers in a 1-week screen as being able to metabolize the sweetener cyclamate to cyclohexylamine (>0.2% of a daily dose), and 31 nonconverters (<0.2% metabolism) were given calcium cyclamate tablets (equivalent to 250 mg cyclamic acid, 3 times daily) for a period of 13 weeks. The metabolism of cyclamate to cyclohexylamine was determined using twice-weekly timed (3 h) urine collections during week 1-3 and 7-13. Urine specimens were collected on all other study days to investigate day-to-day fluctuations in cyclohexylamine excretion. Analyses of the twice weekly timed urine collections showed that subjects recruited as nonconverters essentially remained nonconverters. Of the converters, three showed consistently low metabolism, five showed erratic metabolism, five showed low metabolism initially, which increased during the latter part of the study, and one subject showed consistently high metabolism throughout the study. Analysis of the day-to-day urine specimens showed marked intrasubject variability. The plasma concentrations of cyclohexylamine measured on weeks 1-3 and 7-13 reflected the urine profiles. The highest individual long-term average steady-state excretion values based on the 3-h urine collections and daily samples were 21%, 23%, 25%, 29%, 34%, and 38%. The maximum % metabolism detected in the high converters occasionally reached the value of 60% reported in previous short-term studies, but this high activity was not maintained, and was followed by periods of lower metabolism. The results of this metabolism study support an acceptable daily intake (ADI) of 0-11 mg/kg body weight per day.

Effects of a saccharin and cyclamate mixture on rat embryos.

Sodium saccharin (NaS) and calcium cyclamate (CaC) are artificial sweeteners widely used in food and drink. To evaluate their toxicological effects on preimplantation mammalian embryos, pregnant rats were gavaged with 1.65 mg NaS/kg bw + 3.85 mg CaC/kg bw (DI) or 6.6 mg NaS/kg bw + 15.4 mg CaC/kg bw (D2) on days 1, 2, 3 and 4 of pregnancy (positive vaginal smear = day 1). The female rats were killed on day 5 of the pregnancy (GD 5), maternal organs weighed, and the blastocysts collected, counted and evaluated for gross morphology, cell number and mitotic index. There was no alteration in maternal organ weights, but there was an increase of the cell number/embryo in the dams treated with that NaS + CaC mixtures (D1 = 37.20 +/- 7.96; D2 = 37.26 +/- 10.90) compared to control group (32.24 +/- 6.73). Embryos whose dams were exposed to NaS + CaC may have adapted for implantation into the uterus but more studies are needed to demonstrate this mechanism of action.

Estimated intake of the artificial sweeteners acesulfame-K, aspartame, cyclamate and saccharin in a group of Swedish diabetics.

Few sweetener intake studies have been performed on the general population and only one study has been specifically designed to investigate diabetics and children. This report describes a Swedish study on the estimated intake of the artificial sweeteners acesulfame-K, aspartame, cyclamate and saccharin by children (0-15 years) and adult male and female diabetics (types I and II) of various ages (16-90 years). Altogether, 1120 participants were asked to complete a questionnaire about their sweetener intake. The response rate (71%, range 59-78%) was comparable across age and gender groups. The most consumed 'light' foodstuffs were diet soda, cider, fruit syrup, table powder, table tablets, table drops, ice cream, chewing gum, throat lozenges, sweets, yoghurt and vitamin C. The major sources of sweetener intake were beverages and table powder. About 70% of the participants, equally distributed across all age groups, read the manufacturer's specifications of the food products' content. The estimated intakes showed that neither men nor women exceeded the ADI for acesulfame-K; however, using worst-case calculations, high intakes were found in young children (169% of ADI). In general, the aspartame intake was low. Children had the highest estimated (worst case) intake of cyclamate (317% of ADI). Children's estimated intake of saccharin only slightly exceeded the ADI at the 5% level for fruit syrup. Children had an unexpected high intake of tabletop sweeteners, which, in Sweden, is normally based on cyclamate. The study was performed during two winter months when it can be assumed that the intake of sweeteners was lower as compared with during warm, summer months. Thus, the present study probably underestimates the average intake on a yearly basis. However, our worst-case calculations based on maximum permitted levels were performed on each individual sweetener, although exposure is probably relatively evenly distributed among all sweeteners, except for cyclamate containing table sweeteners.

Cyclamate intake and cyclohexylamine excretion are not related to male fertility in humans.

Cyclamate and its metabolite cyclohexylamine affect male fertility in high dose animal studies, but this affect has not been investigated in epidemiological studies. This paper reports the first epidemiological study designed to investigate the possibility of a relationship between cyclamate and cyclohexylamine and male fertility in humans, in which 405 cases of clinically defined infertility in men and 379 controls were surveyed. Semen evaluation, urine analysis for cyclamate and cyclohexylamine and dietary questionnaires were compared between cases and controls. No evidence was found of a significant association between cyclamate intake and male infertility; neither high cyclamate nor high cyclohexylamine excretion were associated with elevated risk. The lack of association remained after adjusting by age, area of residence, education, total energy intake and other variables. No significant correlations were observed between cyclamate intake, metabolism or excretion, and sperm count and motility. The results demonstrate no effect of cyclamate or cyclohexylamine on male fertility at the present levels of cyclamate consumption.

Artificial sweetener reduces nociceptive reaction in term newborn infants.

BACKGROUND: Sucrose has been shown to have an analgesic effect in preterm and term neonates. Sucrose, however, has a high osmolarity and may have deleterious effects in infants with fructose intolerance. Furthermore, it may favour caries. We therefore investigated the effects of a commercially available artificial sweetener (10 parts cyclamate and 1 part saccharin), glycine (sweet amino acid) or breast milk in reducing reaction to pain as compared with a placebo. SUBJECTS: Eighty healthy term infants, four days old, with normal birth weight. INTERVENTIONS: The infants were randomly assigned to one of four groups: 2 ml sweetener, glycine, expressed breast milk or water were given 2 min before a heel prick for the Guthrie test. The procedure was filmed with a video camera and analysed by two observers who did not know which medication the infant had received. RESULTS: Using a multivariate regression analysis, the following variables had significant correlation with relative crying time and recovery time: behavioural state before the intervention, the pricking nurse, and the type of medication. Relative crying time and recovery time were significantly less in the sweetener group but not in the glycine and the breast milk group. CONCLUSIONS: The artificial sweetener used in our study reduces pain reaction to a heel prick in term neonates, and thus provides an alternative to sucrose. In contrast, glycine tends to increase pain reaction whereas breast milk has no effect.

Intake of saccharin, aspartame, acesulfame K and cyclamate in Italian teenagers: present levels and projections.

The intake of saccharin, aspartame, acesulfame K and cyclamate was assessed in 212 Italian teenagers aged 13-19 in 1996. Total daily intake of intense sweeteners was assessed on the basis of dietary records (14 consecutive days). The sweetener content of sugar-free products (soft drinks, candies, chewing gums, yoghurts, jam and table-top sweeteners) was provided by manufacturers. Sugar-free products were consumed by 77% of the subjects. Mean daily intake among consumers was 0.24 mg/kg body weight (bw) for cyclamate (13 subjects), 0.21 mg/kg bw for saccharin (9 subjects), 0.03 mg/kg bw for aspartame (162 subjects), and 0.02 mg/kg bw for acesulfame K (56 subjects). No subject exceeded the ADI (Acceptable Daily Intake) of an intense sweetener. Projections based on the present levels of use of intense sweeteners in sugar-free products and on the dietary pattern observed in the sample suggest that approaching the ADI could be possible only if subjects with high intakes of both soft drinks and table-top sugar substituted these items with respectively sugar-free beverages and table-top sweeteners containing either saccharin or cyclamate.

Cyclamate consumption in Catalonia, Spain (1992): relationship with the body mass index.

The dietary intake of cyclamate was evaluated in the north-east of Spain in 1992. In a random sample of the Catalan population consisting of 2450 people aged 6-75 years, two 24-h recalls at different seasons were collected; the amount and type of all foods, drinks and drugs consumed were obtained and the total daily intake of cyclamate was expressed in mg/kg body weight (bw), as the average of both 24-h recalls. Eighteen percent of the population consumed cyclamate, and the highest percentage was in men aged 35-44 years (33%). Average daily intake of cyclamate was 0.44 mg/kg bw in the whole population and 2.44 mg/kg bw among consumers. Subjects following a diet reported highest intakes, especially diabetics, and only 0.16% of the sample studied had levels above the Acceptable Daily Intake (ADI). Among consumers, the intake of cyclamate was negatively correlated with Body Mass Index (BMI). The results show the pattern of cyclamate intake in the Spanish population.

[Abuse of artificial sweetener as differential diagnosis of lactose intolerance]. / Süssstoffabusus als Differentialdiagnose der Laktoseintoleranz.

A two year old dystrophic boy with chronic diarrhea was described. At the age of 6 month the boy developed a severe gastroenteritis with a secundary lactase deficiency. Dietary treatment was however not successful and consequently the boy became dystrophic. At last, an abuse of sweetener was diagnosed.

Potential intake of intense sweeteners in Brazil.

A survey of intense sweetener intakes was carried out in the winter of 1990 and summer of 1991 in Brazil. Data on the potential intake of the intense sweeteners aspartame, cyclamate and saccharin were generated, based on a representative sample of 673 individuals who completed a questionnaire designed to collect information on demographic details and habitual usage of sweetener-containing food and drinks. The respondents were randomly chosen among intense sweetener consumers living the cities of Campinas, São Paulo and Curitiba, Paraná. Potential daily intakes by individuals were calculated for each sweetener by combining each person's consumption of sweetener-containing food and beverages with information generated by the determination of the concentrations of the sweeteners used in these products. The data showed that 72% of the studied population consumed saccharin, 67% cyclamate and 40% aspartame. The main reasons alleged for the use of intense sweeteners were weight-control diet (36%), diabetes (35%) and weight loss (23%). Table-top sweeteners were the major source of sweeteners, followed by soft drinks. The median daily intake of aspartame, cyclamate and saccharin represented approximately 2.9, 15.5, and 16-4% of the corresponding ADI, respectively. Diabetics in general had a much higher intake within the studied population.

Intake of intense sweeteners in Germany.

The dietary intake of aspartame, cyclamate, and saccharin was evaluated in Germany (FRG) in 1988/89. In the first part of the study the sweetener intake was evaluated in a representative sample of the population. Complete 24-h records of the amount and type of all foods and drinks consumed were obtained from 2,291 individuals. The total daily intake was calculated for each person from the sweetener content of each product and was expressed in mg/kg body weight (bw). 35.9% of the participants ingested one or more sweeteners on the examination day. Cyclamate and saccharin were the prominent sweeteners because aspartame was at that time permitted only under special regulatory exemption, and products containing acesulfame were not yet available. For users of intense sweeteners the mean intakes of aspartame, cyclamate, and saccharin were 0.15, 2.62, and 0.250 mg/kg bw/day, respectively. At the 90th percentile of intake, i.e., for the heavy consumer, the ingestion of cyclamate and saccharin was about 2.5 times higher. Persons who adhered to a diet (diabetes, weight control) did not ingest sweeteners in substantially higher amounts. Tabletop sweeteners and beverages were the most important sources of sweeteners, and they contributed more than 80% of the total intake. Consumption of sweeteners in excess of the Acceptable Daily Intake (ADI) was rarely observed (saccharin: one person, cyclamate: 16 persons). In the second part of the study, the sweetener intake was further evaluated during a 7-day period in those subjects who in the 1-day study ingested any of the sweeteners in excess of 75% of the ADI. Complete 7-day food records were available from 40 out of the 41 subjects who fulfilled this criterium. In this selected subgroup in which 19 subjects were less than 19 years old, the mean daily intakes of aspartame, cyclamate, and saccharin were 0.13, 4.53, and 0.42 mg/kg body weight (bw), respectively. These levels correspond to 0.33, 41 and 17% of the corresponding ADI values. No subject exceeded the ADI of aspartame or saccharin on any day of the study. For cyclamate, the mean daily intake over the 7-day period exceeded the ADI in 4 subjects. The results indicate that at the time of the study the then valid German sweetener regulation protected the consumer adequately, and that the sweetener intake was in 99.8% of all examined persons within recommended limits.

Acceptable daily intake and the regulation of intense sweeteners.

At the present time there are four intense sweeteners that are available in a number of countries: acesulfame-K, aspartame, cyclamate and saccharin. Extensive toxicity databases are available on each sweetener and these have been assessed by both national and international regulatory authorities. This review considers briefly the critical toxicity of each sweetener that is the basis for establishing the no adverse effect level in animal studies. The calculation of an acceptable daily intake (ADI) for human intake employs a large safety factor applied to the no-effect level. The magnitude of the safety factor for each sweetener is discussed in relation to the ADI values recommended by the Scientific Committee for Food in 1985.