RESUMEN
This paper principally addresses the question of whether exposure to food additives/contaminants is likely to be higher in children than adults. Food consumption surveys conducted in the United Kingdom indicated that 99% of infants were receiving some solid food at 6 months of age (mean age of introduction 13 weeks), mainly 'family' foods not specifically produced for infants. On a body weight basis, young children, age 1 1/2-4 1/2 years, were shown to consume more than adults most notably of dairy products, puddings and confectionery (up to five times adult intakes) and of soft drinks (up to 16 times adult values). Two examples of risk assessments are given, for chlorinated dibenzodioxins and saccharin, where the intake was highest in children, in some cases exceeding the Provisional Tolerable Weekly Intake or Acceptable Daily Intake, respectively. The necessary risk management measures taken are discussed.
Asunto(s)
Dieta , Aditivos Alimentarios/administración & dosificación , Adolescente , Adulto , Factores de Edad , Bebidas , Niño , Preescolar , Dioxinas/administración & dosificación , Relación Dosis-Respuesta a Droga , Aditivos Alimentarios/efectos adversos , Contaminación de Alimentos , Humanos , Lactante , Persona de Mediana Edad , Necesidades Nutricionales , Sacarina/administración & dosificaciónRESUMEN
The UK has developed considerable experience in the estimating additive intake over the past 20 years. The earliest approach involved collecting large amounts of detailed information on additive concentrations and aimed to provide accurate estimates of intake for all additives in a given class. This has been replaced in recent times by a hierarchical approach which is applied to selected additives following an initial prioritization. Initial intake estimates are made using readily available data and conservative assumptions about additive occurrence and food consumption. More refined calculations are not necessary if the initial estimate shows that intake is well below the Acceptable Daily Intake. Once the level of intake has been established, it is only necessary to repeat the estimation if market information shows that there have been substantial changes in additive usage or food consumption. A similar approach is recommended for adoption across the European Union.
Asunto(s)
Aditivos Alimentarios/administración & dosificación , Alimentos , Aditivos Alimentarios/análisis , Análisis de los Alimentos , Humanos , Legislación Alimentaria , Edulcorantes/administración & dosificación , Reino UnidoRESUMEN
1. Indole, p-cresol and phenol are microbial amino acid metabolites which show co-carcinogenic or promoting activity in animal studies. Their involvement in the development of human bladder cancer has been determined by measuring the urinary excretion of indican (indoxyl sulphate) and conjugated phenols. 2. Thirty-two patients (22 males, 10 females) with histologically confirmed carcinoma of the urinary bladder and a similar number of age and sex matched controls took part in the study. The excretion of indican, p-cresol and phenol showed wide interindividual variability, but did not differ significantly between the two groups. 3. The findings indicate that these endogenous metabolites do not contribute significantly to the development of human bladder cancer.
Asunto(s)
Cocarcinogénesis , Cresoles/orina , Indicán/orina , Fenoles/orina , Neoplasias de la Vejiga Urinaria/inducido químicamente , Anciano , Anciano de 80 o más Años , Carcinógenos , Carcinoma de Células Transicionales/inducido químicamente , Carcinoma de Células Transicionales/orina , Femenino , Humanos , Masculino , Persona de Mediana Edad , Fenol , Neoplasias de la Vejiga Urinaria/orinaRESUMEN
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.
Asunto(s)
Aminoácidos/orina , Bacterias/metabolismo , Sacarina/toxicidad , Animales , Peso Corporal/efectos de los fármacos , Cresoles/orina , Relación Dosis-Respuesta a Droga , Ingestión de Líquidos/efectos de los fármacos , Ingestión de Alimentos/efectos de los fármacos , Humanos , Indicán/orina , Masculino , Fenol , Fenoles/orina , Ratas , Ratas Endogámicas , Factores de TiempoRESUMEN
Administration of a diet containing 7.5% saccharin to adult male rats for 40 days caused a three- to four-fold increase in the daily excretion of indican and rho-cresol. Indican is formed from indole which is a microbial metabolite of tryptophan, whilst rho-cresol is formed by the gut flora from tyrosine. The excretion of phenol, which is also a microbial metabolite of tyrosine, was abolished by saccharin administration for 40 days. Analysis of urines collected at 13, 18 and 24 months during a two-generation cancer bioassay showed that these changes occur throughout the life of saccharin-treated rats. These data indicate that saccharin changes the metabolism of amino acids by the gut flora, leading to an increased formation of products known to have promoting or co-carcinogenic properties.
Asunto(s)
Aminoácidos/metabolismo , Bacterias/metabolismo , Sacarina/toxicidad , Animales , Cocarcinogénesis , Cresoles/orina , Dieta , Indicán/orina , Intestinos/microbiología , Masculino , Fenoles/orina , Ratas , Ratas Endogámicas , Sacarina/orina , Triptófano/metabolismo , Neoplasias de la Vejiga Urinaria/inducido químicamenteRESUMEN
The metabolism and pharmacokinetics of intravenously administered theophylline (100 mg) have been investigated in three healthy male volunteers who consumed 6 bottles/day of a cola beverage, in addition to their usual intake of methylxanthines, for 7 days prior to and during the study. Five urinary metabolites were detected in addition to unchanged theophylline, that is 3-methylxanthine, 1,3-dimethyluric acid, 1-methyluric acid, and two minor unknown metabolites. The elimination of theophylline, 1,3-dimethyluric acid, 1-methyluric acid, and the two unknowns was described by first-order kinetics, whereas that of 3-methylxanthine was described by Michaelis-Menten kinetics. The results have been compared with those previously obtained in the same volunteers while consuming their usual intake of methylxanthine-containing foods and beverages, and this shows that the addition of extra methylxanthines to the diet does not influence the disposition of theophylline. This is in marked contrast to the effect of deprivation of dietary methylxanthines on theophylline metabolism. The results are discussed in terms of the influence of methylxanthines on theophylline metabolism, and of its possible dose-dependency.